Main Menu

Advertisement

Vitamins

A 32-year-old body builder has decided to go on a diet consisting of egg whites to ensure only proteins for muscle growth. After a few weeks he experiences decreased energy and is found to be hypoglycemic. A nutritionist tells the patient that he most likely has the deficiency of vitamin Biotin. Which of the following enzymes is unable to catalyze its step in synthesizing glucose from pyruvate?

A) Pyruvate carboxylase

B) Phospho enol pyruvate carboxykinase

C) Glucose-6-phosphatase

D) Fructose 1, 6 bisphosphatase

E) Phosphoglycerate kinase.

The correct answer is- A) – Pyruvate carboxylase.

Biotin deficiency is very common in bodybuilders, who consume raw egg whites. The Raw egg whites contain Avidin, a glycoprotein that strongly binds with biotin and prevents its absorption. Once a biotin-Avidin complex forms, the bond is essentially irreversible; the biotin-Avidin complex is not broken during passage of the food bolus through the stomach and intestines. As a result, biotin is not liberated from food, and the biotin-Avidin complex is lost in the feces. Thus, the ingestion of large quantities of raw egg white over a long period can result in a biotin deficiency. Cooking egg white denatures Avidin, rendering it susceptible to digestion and therefore unable to prevent the absorption of dietary biotin.

Biotin functions to transfer carbon dioxide in a small number of carboxylation reactions. Biotin is attached at the active site of carboxylases.

Each Biotin dependent carboxylase catalyzes an essential metabolic reaction:

1) Pyruvate carboxylase

Pyruvate carboxylase is a critical enzyme in gluconeogenesis—the formation of glucose from sources other than carbohydrates, for example, amino acids. Oxaloacetate formed from pyruvate can be utilized in many other ways depending upon the need of the cell (Figure-3)

Reaction catalyzed by pyruvate carboxylase

Figure-1 -Carboxylation of pyruvate to Oxaloacetate, catalyzed by Pyruvate carboxylase, is the first step of gluconeogenesis.

The other examples where Biotin is required as a coenzyme are:

2) Acetyl-CoA carboxylase (ACC) catalyzes the binding of bicarbonate to acetyl-CoA to form malonyl-CoA (Figure-2). Malonyl-CoA is required for the synthesis of fatty acids.

Reaction-catalyzed-by-Acetyl-co-A-carboxylase

Figure-2 -The carboxylation of Acetyl co A to form Malonyl co A, catalyzed by Acetyl co A carboxylase is the first and the rate limiting step in fatty acid synthesis.

3) Propionyl-CoA carboxylase catalyzes essential steps in the metabolism of certain amino acids, cholesterol, and odd chain fatty acids (fatty acids with an odd number of carbon molecules).

Fate of propionyl co A

Figure- 3-showing the fate of Propionyl co A

Propionyl co A is converted first to D- Methyl malonyl co A and then to its L isomer, ultimately to succinyl co A for complete utilization in the TCA cycle (Figure-3).

Anaplerotic reactions catalyzed by biotin dependent pyruvate carboxylase (PC) and Propionyl-coenzyme A carboxylase (PCC) regenerate oxaloacetate for the citric acid cycle.

As regards other options

B) Phospho enol pyruvate carboxykinase- Catalyzes the conversion of Oxaloacetate to phosphoenol pyruvate, it is an enzyme of pathway of gluconeogenesis but it is not a biotin dependent enzyme

C) Glucose-6-phosphatase catalyzes the last step of conversion of glucose-6-Phosphate to free glucose, but it is also not biotin dependent enzyme.

D) Fructose 1, 6 bisphosphatase- catalyzes the conversion of fructose1, 6 bisphosphate to Fructose 6 Phosphate; it is also not a biotin dependent enzyme.

E) Phosphoglycerate kinase- is a common enzyme, both for the pathways of glycolysis and gluconeogenesis. It catalyzes the reversible conversion of 1, 3 bisphosphoglycerate to 3, phosphoglycerate, ATP is formed by substrate level phosphorylation in glycolysis. ATP is consumed in the reverse reaction, in the pathway of gluconeogenesis.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

 

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- Biotin is a coenzyme for reactions involving:

A) Decarboxylation                                                    

B) Carboxylation

C) Transamination                                                     

D) Deamination                     

E) Transmethylation

Q.2- Folic acid is important for which of the following processes?

A) Fatty acid oxidation                                                           

B) Fatty acid synthesis

C) Gluconeogenesis                                                   

D) One carbon metabolism

E) Glycogenesis                      

Q.3- Sideroblastic anemia is observed in the deficiency of which of the following?

A) Thiamine                                                               

B) B6

C) B12                                                                                    

D) Niacin

E) Vitamin K                           

Q.4- Xanthurenic acid excretion (Tryptophan loading ) test is carried out to determine the deficiency of:

A) Riboflavin                                                              

B) B6

C) Niacin                                                                    

D) Biotin      

E) B12             

Q.5- A 45-year-old chronic alcoholic male has been brought to medical emergency in a semi-conscious state. Blood lactate level is high. Which of the following vitamins can be used as a part of the treatment?

A) Vitamin C                                                               

B) Vitamin B12

C) Thiamine                                                               

D) Folic acid   

E) Pantothenic acid                

Q.6- Which of the following is the coenzyme form of Thiamine?

A) TPP (Thiamine pyrophosphate)                                                                 

B) TMP (Thiamine mono phosphate)

C) TTP  (Thiamine triphosphate)                                                                    

D) Free thiamine

E) TAD (Thiamine adenine dinucleotide).     

Q.7- A 20-year-old male presents with hypertension. He has been prescribed a drug that work by inhibiting the synthesis of catecholamines. Which of the following vitamins participates in the synthesis of catecholamines?

A) Vitamin C                                                               

B) Vitamin B12

C) Niacin                                                                    

D) Folic acid                           

E) Biotin

Q.8-Which of the following is aTPP dependent enzyme?

A) Lactate dehydrogenase                                         

B) Glucokinase

C) Transketolase                                                        

D) Glutathione reductase

E) Glutamate dehydrogenase

Q.9- A 30- year-old pregnant female presents to her obstetrician for a prenatal visit. She has been conscious of her weight gain and has not been taking a multivitamin. Her red blood cells are found to have decreased Glutathione reductase function. Glutathione reductase requires:

A) TPP                                                                         

B) Pyridoxine

C) Riboflavin                                                              

D) B12

E) Pantothenic acid                                        

Q.10- Which of the following is required as a coenzymes in the conversion of Histidine to Histamine?

A) TPP                                                                         

B)NAD+

C) Vitamin C                                                               

D) Pyridoxal phosphate

E) Folic acid    

Key to answers

1)      B

2)      D

3)      B

4)      B

5)      C

6)      A

7)      A

8)      C

9)      C

10)   D

 

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Case details

A 4 -year-old boy was brought for consultation for hematuria, edema of lower extremities as well as swollen right leg. He was the 12th born in a poor family, where one previous child died from malnutrition and dehydration in the period of infancy. The child was fed only with cow’s milk and biscuits. From the period of five months, the boy manifested irritability, sweating, poor appetite and cried when somebody touched him

At admission the baby was afebrile, pale, and malnourished. Clinical evaluation showed no organomegaly, no neurological signs, gingival bleeding was there and only one tooth was present. The child was diagnosed with ‘Scurvy’, which is a clinical sate of severe vitamin C deficiency. Vitamin C has an important role in the body, besides performing multiple functions, and acting as an antioxidant, it is also required as a coenzyme for specific reactions.

Which ‘one’ of the following conversions is inhibited in scurvy?

A. Conversion of Pyruvate to Acetyl co A

B. Conversion of Propionyl co A to succinyl co A

C. Conversion of Homocysteine to Methionine

D. Conversion of Proline to Hydroxyproline

E. Conversion of Succinate to fumarate.

The correct answer is D- Conversion of Proline to Hydroxyproline.

Basic concept

Vitamin C dependent Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen. The proline to hydroxyproline conversion reaction can be represented as follows:

 Hydroxylation of Proline

Figure- Hydroxylation of proline is an essential prerequisite for collagen synthesis. The hydroxylation of Lysine is also carried out in the same manner.

Deficiency of vitamin C leads to impaired collagen synthesis, causing capillary fragility, poor wound healing, and bony abnormalities in affected adults and children.

The functions of vitamin C can be summarized alphabetically as follows:

A) It is an antioxidant and is also required for the amino acid metabolism such as metabolism of tryptophan and tyrosine.

B) Vitamin C is required for Bone formation, Bile acid synthesis and Brain function

C) It is required for the synthesis of Collagen, Carnitine, Complement and Catecholamines.

D) Drug detoxification- It is a component of many drug-metabolizing enzyme systems, particularly the mixed-function oxidase systems.

E) Enzymes– Vitamin C is the coenzyme for two groups of hydroxylases. These are copper-containing hydroxylases and the α-ketoglutarate-linked iron-containing hydroxylases. 

F) Folic acid metabolism- Ascorbic acid is required for reducing Folic acid to its tetrahydrofolate form. Thus it helps in the maturation of red blood cells.

G) General body growth- Vitamin C has a protective role and because of its role in disease prevention, it stimulates general body growth.

H) Vitamin C is helpful in the reconversion of met haemoglobin to haemoglobin. Vitamin C is also a cofactor in the synthesis of peptide hormones, corticosteroids, and aldosterone.

I) The vitamin C has an important role in the absorption and conversion of Iron to its storage form. This may contribute to the anemia seen with vitamin C deficiency.

Vitamin C promotes Immunity and has been proposed to have pharmacological benefits in preventing cancer, infections, and the common cold.

As regards other options

A. Conversion of Pyruvate to Acetyl co A- requires Thiamine (TPP), Pantothenic acid (CoASH), Lipoic acid, FAD and NAD + as coenzymes. The reaction is catalyzed by Pyruvate dehydrogenase complex, which is a multienzyme complex.

B. Conversion of Propionyl co A to succinyl co A is a multistep process. Biotin and vitamin B12 are required for the metabolism of Propionyl co A.

C. Conversion of Homocysteine to Methionine- requires the presence of Methylcobalamine and folic acid, the reaction is catalyzed by Methionine synthase.

E. Conversion of Succinate to fumarate- is catalyzed by succinate dehydrogenase; the enzyme requires the presence of FAD (Riboflavin) for its action.

Thus in vitamin C deficiency, the conversion of proline to hydroxyproline is inhibited.

For further reading

Check the following links

Functions of Vitamin C

http://www.namrata.co/a-to-i-of-vitamin-c-functions-of-vitamin-c-simplified/

Vitamin C deficiency

http://www.slideshare.net/namarta28/vitamin-c-deficiency

 

 

 

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Click  the link to view the presentation

http://www.slideshare.net/namarta28/vitamin-b12-chemistry-functions-and-clinical-significance

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

A postoperative patient on intravenous fluids develops lesions in the mouth (angular stomatitis). Urinalysis indicates an excretion of 15 μg riboflavin/mg creatinine, which is abnormally low. Which of the following TCA cycle enzymes is most likely to be affected?

A. Citrate synthase

B. Isocitrate dehydrogenase

C. Fumarase

D. Malate dehydrogenase

E. Succinate dehydrogenase

Details– E) – Succinate dehydrogenase is the correct answer.

The patient has demonstrated a deficiency in riboflavin (urinary excretion of less than 30 μg/mg creatinine is considered clinically deficient). Vitamin B2 deficiency is frequent in chronic alcoholics.  It can also occur in patients with chronic liver diseases, and in hospitalized patients who receive total parenteral nutrition (TPN) with inadequate riboflavin supplementation. Riboflavin is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin supports energy production by aiding in the metabolism of fats, carbohydrates, and proteins . Characteristic symptoms of riboflavin deficiency include lesions of the skin, especially in the corners of the mouth (angular stomatitis) and a red, sore fissured tongue (figure-1).

 Angular stomatitis

Figure-1- Angular stomatitis

Riboflavin functions in several different enzyme systems. Two derivatives, riboflavin 5′ phosphate (flavin mononucleotide [FMN]) and riboflavin 5′ adenosine diphosphate (flavin adenine dinucleotide [FAD]), are the coenzymes that unite with specific apoenzyme proteins to form flavoprotein enzymes.

 Structure of Riboflavin

Figure-2- Structure of Riboflavin. It contains D- ribitol, and the Isoalloxazine ring( flavin nucleus)

FMN and FAD function as coenzymes for a wide variety of oxidative enzymes and remain bound to the enzymes during the oxidation-reduction reactions. Flavins can act as oxidizing agents because of their ability to accept a pair of hydrogen atoms. Reduction of isoalloxazine ring (FAD, FMN oxidized form) yields the reduced forms of the flavoprotein (FMNH2 and FADH2).

Enzymes that contain flavin adenine dinucleotide (FAD) or flavin-mononucleotide (FMN) as prosthetic groups are known as flavoenzymes.

Succinate dehydrogenase is the only FAD dependent enzyme in TCA cycle. Succinate dehydrogenase catalyzes the conversion of succinate to fumarate. The reaction catalyzed can be represented as follows

 Succinate dehydrogenase

Figure-3- Reaction catalyzed by succinate dehydrogenase

As regards other options

Citrate synthase catalyzes the condensation of acetyl co A and oxaloacetate to form Citrate (Figure-4); it does not require FMN or FAD as a coenzyme.

 TCA cycle

Figure-4- TCA cycle enzymes and the steps of TCA cycle. (IDH is isocitrate dehydrogenase)

Isocitrate and malate dehydrogenase are NAD + dependent enzymes.

Fumarase catalyzes the conversion of Fumarate to malate; it also does not require riboflavin as a coenzyme.

Thus out of all the given options, Succinate dehydrogenase is the only TCA cycle enzyme, the activity of which can be affected in riboflavin deficiency.

 

 

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- A 23-year-old male, golden gloves boxing contender presents with a metabolic disorder. He describes his training regimen that involves consuming a dozen raw eggs a day for a protein. Raw eggs contain a protein called Avidin, with an extremely high affinity for a cofactor, required by propionyl co A carboxylase, Acetyl co A carboxylase and pyruvate carboxylase. The patient is deficient in which of the following cofactors?

A. Cobalamine

B. Biotin

C. Folic acid

D. Pyridoxal Phosphate

E. TPP

Q.2- Which of the following enzymes requires Vitamin K for its action?

A. Succinate dehydrogenase

B. Pyruvate carboxylase

C. Epoxide reductase

D. Dihydrofolate reductase

E. Lactate dehydrogenase

Q.3- Oral contraceptives are known to lower blood levels of vitamin B6. Which of the following conversion process might be directly affected?

A. Phenyl alanine to Tyrosine

B. Pyruvate to Oxalo acetate

C. Dopamine to norepinephrine

D. Histidine to histamine

E. Pyruvate to Lactate

Q.4- Which of the following TCA cycle enzymes require FAD as a cofactor?

A. Isocitrate dehydrogenase

B. Alpha ketoglutarate dehydrogenase

C. Succinate dehydrogenase

D. Malate dehydrogenase

E. Succinate thiokinase

Q.5- A 20-year-old female, a known alcoholic has been brought to the emergency department with respiratory distress. Bilateral crepitations are felt in the lungs, neck veins are engorged and X-ray chest shows dilated heart. She has been diagnosed with ‘Cardiac Beri-Beri’. Which of the following reactions might have been affected?

A. Pyruvate to Malic acid

B. Pyruvate to Acetyl co A

C. Pyruvate to Oxaloacetate

D. Pyruvate to lactate

E. Pyruvate to Alanine

Q.6- A bone marrow aspirate of a strictly vegetarian female, confirms the suspicion that she has a megaloblastic anemia because it showed a greater than normal number of red and white blood cell precursors, most of which were larger than normal. What is the cause of megaloblastic anemia in this patient?

A. Vitamin C deficiency

B. Folate toxicity

C. Vitamin B12 deficiency

D.  B6-P deficiency

E.  Vitamin K toxicity

Q.7- A 45-year-old female presents to her primary care doctor with fatigue and tingling/numbness in her extremities (bilateral). Examination reveals a beefy red and fissured tongue. Further evaluation reveals a low Glutathione reductase activity in the red blood cells. Which of the following vitamin deficiencies could have caused her symptoms?

A. Vitamin C deficiency

B. Niacin deficiency

C. Vitamin B2 deficiency

D.  B6-P deficiency

E.  Biotin deficiency

Q.8- A 60-year-old chronic smoker and alcoholic man presents with epigastric discomfort and recurrent diarrhea. Clinical examination reveals memory disorientation, stomatitis, glossitis, esophagitis, and exfoliative dermatitis. Treatment with nicotinamide 500 mg daily has been initiated. Which of the following conversions might not have been affected?

A. Succinate to Fumarate

B. Malate to Oxaloacetate

C. Pyruvate to Acetyl co A

D. Pyruvate to lactate

E. Dihydrofolate to Tetra hydro folate

Q.9-   A 12-year-old boy develops convulsions. After running an encephalogram (EEG), a neurologist determines that he has Epilepsy. He is prescribed with Benzodiazepine which promotes the activity of GABA. GABA is derived from glutamic acid via which of the following biochemical reactions?

A. Deamination

B. Decarboxylation

C. Transamination

D. Carboxylation

E. Hydroxylation

Q.10- A 3 –year-old girl has been brought for consultation. She is well below the 5th percentile for both height and weight with multiple rachitic deformities of the skeleton to include severe bowing of the tibias bilaterally, pigeon chest and thickened/widened wrists bilaterally. Which of the following vitamins can be recommended as a part of treatment?

A. Vitamin D

B. Biotin

C. Folic acid

D. Pyridoxal Phosphate

E. TPP

Q.11- A 2 –year-old child presented with chronic cough and Bronchitis, growth failure and passage of light-colored, foul-smelling stools. Mother of the child reported that the child was finding it difficult to locate things in the dim light and during night-time. Which of the following vitamins might be deficient in this child?

A. Vitamin A

B. Vitamin D

C. Vitamin C

D. Vitamin E

E. Vitamin K

Q.12- A term infant is born and does well with breast-feeding. Two days later, the mother calls frantically because baby is bleeding from the umbilical cord and nostrils. Which of the following vitamins might be deficient in this baby?

A. Vitamin A

B. Vitamin D

C. Vitamin C

D. Vitamin E

E. Vitamin K

Q.13- A 45 -year-old male has been brought to the emergency department after a family member found him extremely confused and disoriented. He has an unsteady gait and strange irregular eye movements. Upon extensive work up, he has been diagnosed with Wernicke-Korsakoff syndrome. Which of the following vitamins might be deficient?

 A. TPP

B. Biotin

C. Folic acid

D. Pyridoxal Phosphate

E. Niacin

Q.14- Choose the odd one out-

A. Vitamin A

B. Vitamin D

C. Vitamin C

D. Vitamin E

E. Vitamin K

Q.15Ascorbic acid is required in the effective utilization of all  of the following amino acids except

A. Methionine                                                                             

B. Tryptophan

C. Tyrosine                                                                                         

D. Proline

E. Lysine

Q.16- Which of the following vitamins requires intrinsic factor for its absorption?

A. Cobalamine

B. Biotin

C. Folic acid

D. Pyridoxal Phosphate

E. TPP

Q.17- Which of the following vitamins can act without phosphorylation-?

A. Pyridoxine

B. Lipoamide

C. Niacin

D. Thiamine

E. None of the above.

Q.18- Scurvy is due to impaired———— synthesis

A. Collagen

B. Prothrombin

C. Hemoglobin

D. Elastin

E. Albumin

Q.19- Neurological manifestations are present in

A. Dry Beri- Beri

B.B6 deficiency

C. B12 deficiency

D. All of the above

E. None of the above

Q.20- Which of the following vitamins is an integral component of coenzyme A that allows two carbon units to enter the TCA cycle?

A. Thiamin

B. Pantothenic acid

C. Biotin

D. Vitamin A

E. Niacin

Key to answers

1)- B,2)-C,3)-D, 4)-C,5)-B,6)-C,7)-C,8)-A,9)-B,10)-A,11)-A,12)-E,13)-A,14)-C,15)-A,16)-A,17)-B,18)-A,19)-D,20)-B

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- Which of the following cofactors is correctly matched with the vitamins it is derived from?

A. NADH- Vitamin B2                                                                     

B. FADH2- Vitamin B3

C. Pyridoxal Phosphate- B1                                                         

D. TPP- Vitamin B1          

E. Pantothenic acid- Vitamin B6

Q.2- Which of the following coenzymes is required during the conversion of Glutamic acid to gamma amino butyric acid (GABA)?

A. TPP                                                                                                  

B. NAD+

C. Vitamin C                                                                                       

D. Pyridoxal phosphate

E. FMN

Q.3- Which of the following compounds is a recipient of the one carbon fragments that tetra hydro folate receives and transfers?

A. Serine                                                                                             

B. Formaldehyde            

C. Glycine                                                                                           

D. Formimino glutamate (FIGLU)

E. Tryptophan

Q.4- Which of the following is a compound formed from hydroxylation requiring vitamin C and subsequent methylation?

A. Histamine                                                                                     

B. GABA

C. Epinephrine                                                                                 

D. Carnitine

E. Serotonin                      

Q.5- Which amino acid can be converted to non adenine portion of NAD+?

A. Histidine                                                                                        

B. Tyrosine

C. Tryptophan                                                                                  

D. Arginine

E. Phenyl alanine                             

Q.6- A 25-year-old female who is 10 weeks pregnant presents with intractable vomiting from morning sickness. She is admitted for intravenous glucose administration and hydration. Which of the following vitamins can also be tried for treating the morning sickness?

A. Vitamin C                                                                                      

B. Vitamin B12

C. Pyridoxal –P                                                                                 

D. Folic acid        

E. Vitamin B12  

Q.7- A 60 –year-old female presents with severe back pain for the past week, she is diagnosed with osteoporosis, a condition resulting from calcium depletion in bones. As treatment which of the following vitamins can be prescribed?

A. Vitamin A                                                                                      

B. Vitamin D

C. Vitamin E                                                                                       

D. Vitamin K      

E. Vitamin C       

Q.8- A 30- year-old pregnant female presents to her obstetrician for a prenatal visit. She has been conscious of her weight gain and has not been taking a multivitamin. Her red blood cells are found to have decreased transketolase function. Transketolase requires:

A. TPP                                                                                                  

B. Pyridoxine

C. Folate                                                                                             

D. B12  

E. FAD                  

Q.9- A 20-year-old male presents with muscle weakness, and extreme fatigue. After an extensive work up he is diagnosed with carnitine deficiency. Which of the following vitamins participates in the endogenous synthesis of carnitine?

A. Vitamin C                                                                                      

B. Vitamin B12

C. Pyridoxal –P                                                                                 

D. Folic acid

E. Biotin                               

Q.10- Which of the following is not a clinical outcome of niacin deficiency?

A.  Diarrhea                                                                                       

B.  Night blindness

C. Dermatitis                                                                                     

D. Dementia      

E. Death              

Q.11- Which out of the following is not a TPP dependent enzyme?

A. PDH complex                                                                                               

B. Glutathione reductase            

C. α- Keto glutarate dehydrogenase complex                    

D. α- Keto acid dehydrogenase complex

E. Transketolase

Q.12- Methyl malonic aciduria is a disorder associated with impaired metabolism of methyl malonic acid. Which of the following vitamins participates in its metabolism to form succinyl co A?

A. Vitamin C                                                                                      

B. Vitamin B12

C. Pyridoxal –P                                                                                 

D. Folic acid

E. Niacin                                              

Q.13- Which of the following vitamins is required as a coenzyme for the activity of dihydrofolate reductase?

A. Vitamin C                                                                                      

B. Vitamin B12

C. Pyridoxal –P                                                                                 

D. Folic acid

E. Niacin                                              

Q.14- Which of the following set of vitamins participates in the synthesis of catecholamines?

A. Vitamin B6 and C                                                                        

B. Vitamin B12 and Folic acid

C. Pyridoxal –P and Niacin                                                           

D. Folic acid and Riboflavin

E. Vitamin B6 and B12    

Q.15- The conversion of pyruvate to oxaloacetate requires the presence of:

A. Biotin                                                                                              

B. Vitamin B12

C. Pyridoxal –P                                                                                 

D. Folic acid        

E. Niacin                              

Q.16- Which of the following forms of vitamin A is required for vision?

A.  All cis retinal                                                                                

B. All Trans retinal

C. 11- Cis retinal                                                                               

D. 11- Cis retinol

E. Any of the above                                                                                                                                       

Q.17- Which of the followings is a FAD dependent enzyme?

 A. Lactate dehydrogenase                                                         

B. PDH complex

C. Transketolase                                                                              

D. Glutathione reductase

E. Dihydrofolate reductase                                                                                                                         

Q.18- Which vitamin deficiency is associated with neural tube defects?

A. Vitamin C                                                                                      

B. Vitamin B12

C. Pyridoxal –P                                                                                 

D. Folic acid        

E. Niacin                                                                                                                              

Q.19- Hyperhomocysteinemia can be treated by supplementation with:

A. Folic acid                                                                                        

B. Vitamin B12

C. Vitamin B6-P                                                                                

D. All of the above

E. None of the above                                                                                                                                    

Q.20- The active form of vitamin D is:

A. Calcidiol                                                                                         

B. Calcitriol

C. Cholecalciferol                                                                            

D. Any of the above

E. None of the above

 

Key to answers

 1) -D, 2)- D, 3)-C, 4)- C, 5)- C, 6)-C, 7)- B, 8)- A, 9)- A, 10)- B, 11)-B,12)- B, 13)-E, 14)-A,15)-A,16)-C,17)-D,18)-D,19)-D, 20)- B.

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- A 10-year-old male presents with muscle cramping and dark urine after rigorous exercise. He is found to have a deficiency of lactate dehydrogenase. This enzyme catalyzes interconversion of lactate and pyruvate based upon the availability/ absence of oxygen. Which of the following coenzymes is needed for this action?

A. NAD+

B. FAD

C. TPP

D. Adenosyl cobalamine

E. Pyridoxal phosphate

Q.2- An infant presents with growth retardation, weak muscle tone and lethargy. He is diagnosed with pyruvate carboxylase deficiency. Which of the following vitamins is required as a coenzyme for its action?

A. Vitamin C

B. Biotin

C. Pantothenic acid

D. Riboflavin

E. Niacin

Q.3- A 70-year-smoker presents with weight loss, blood in the sputum, and fatigue. Imaging shows a nodule in his lung that is diagnosed as cancer by biopsy. It has been proposed that reactive oxygen species may induce mutagenesis and contribute to the initiation of cancer. Which of the following is an antioxidant vitamin?

A. Vitamin K

B. Vitamin D

C. Folic Acid

D. Vitamin C

E. Vitamin B12

Q. 4- An infant is born with a congenital brain malformation and dies shortly after birth. An enzyme screen shows that the patient was deficient in pyruvate dehydrogenase complex, the enzyme that catalyzes the conversion of pyruvate to Acetyl co A. Which of the following coenzymes is required for its action?

A. Biotin

B. Niacin

C. Vitamin B12

D. Vitamin K

E. Folic acid.

Q.5- A 60- year-old female presents with burning on urination, fever, and chills. She is admitted for treatment of a severe urinary tract infection and is placed on an antibiotic. After a few days of taking this antibiotic, she develops bleeding gums and oozing of blood from her intravenous line site. Depletion of which of the following vitamins is most likely to be responsible for her symptoms?

A. Vitamin A

B. Vitamin D

C. Vitamin E

D. Vitamin K

E. Vitamin C

Q.6- Oxidative deamination is a process of removal of amino group of amino acids in the form of ammonia. It is two-step process involving oxidation followed by deamination. Which of the following vitamins is required as a coenzyme for this process?

A. Pyridoxal phosphate

B. FMN/FAD

C. NAD +

D. TPP

E. Lipoic acid

Q.7- “Tryptophan load test’ is carried out to determine the underlying deficiency of:

 A. Vitamin B6

B. Biotin

C. Niacin

D. Vitamin B12

E. Folic acid

Q.8- What is the link between intake of polished rice and sudden cardiac failure?

A. Riboflavin deficiency

B. Thiamin deficiency

C. Folic acid deficiency induced hyperhomocysteinemia

D. Vitamin C deficiency

E. Niacin deficiency

Q-9 – “Histidine load test” is carried out to determine the deficiency of which of the following vitamins?

A. Folic acid

B. Vitamin B12

C. Pyridoxal- P

D. Vitamin D

E. Riboflavin

Q.10- ‘Burning feet syndrome’, is associated with a deficiency of:

A. Lipoic acid

B. Pyridoxal- P

C. Pantothenic acid

D. Niacin

E. Vitamin C.

Q.11- Sideroblastic anemia is observed in the deficiency of:

A. Vitamin C

B. Folic acid

C. Vitamin B12

D. Pyridoxal-P

E. Vitamin K

Q.12- As a hormone, vitamin D has three target tissues. Which are they?

A. Kidney, small intestine, bone                               

B. Heart, blood, bone marrow

C. Kidney, liver, brain                                    

D. Small intestine, liver, fat cells

E. Liver, spleen and bone marrow

Q.13- Epileptiform convulsions in infants are found in the deficiency of-

A. Riboflavin                                                                      

B. Thiamine

C. Niacin                                                                                              

D. Pyridoxine

E. Thiamine

Q.14- Which of the following vitamins is required for the transfer of one carbon fragments?

A. Vitamin C

B. Folic acid

C. Biotin

D. Niacin

E. Riboflavin

Q.15- Which of the following vitamins is used therapeutically as a lipid lowering drug?

A. Vitamin C

B. Folic acid

C. Biotin

D. Niacin

E. Riboflavin

Q.16- The deficiency of which of the following vitamins, is responsible for the clinical manifestations of Egg white injury?

A. Vitamin C

B. Folic acid

C. Biotin

D. Niacin

E. Riboflavin

Q.17- Which vitamin deficiency leads to impaired coagulation of blood ?

A. Vitamin C

B. Vitamin D

C. Biotin

D. Niacin

E. Vitamin K

Q.18- Transamination is a process of transfer of α- amino group from a donor amino acid to an acceptor α- keto acid for the formation of a new amino acid and a new keto acid. This process is a reversible process catalyzed by Transaminases that require—- as a coenzyme.

A. Vitamin C

B. Folic acid

C. Vitamin B12

D. Pyridoxal-P

E. Vitamin K

Q.19-   The inner mitochondrial membrane is impermeable to fatty acids. Carnitine acts as a transporter for internalization of fatty acids in to the matrix where the beta oxidation of fatty acids takes place to provide energy to the body. Which of the following vitamins is required as a coenzyme for the synthesis of carnitine?

A. Vitamin C

B. Folic acid

C. Vitamin B12

D. Pyridoxal-P

E. Vitamin K

Q.20- The reaction of TCA cycle that converts Succinate to fumarate requires the participation of—– as a coenzyme:

A. Vitamin C

B. Folic acid

C. Biotin

D. Niacin

E. Riboflavin

 

Key to Answers

1)-A, 2)-B, 3)-D, 4)- B, 5)-D, 6)-B, 7)- A, 8)- B, 9)- A, 10)-C, 11)-D, 12)-A, 13)-D, 14)- B, 15)-D, 16)- C,17)- D, 18)-D, 19)- A, 20)- C.

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Causes of vitamin K deficiency

  • Vitamin K deficiency can result from lack of vitamin K in the diet. In adults, low dietary intake alone is seldom reason for severe vitamin K deficiency but may become common in association with the use of broad-spectrum antibiotics.
  • From disorders that impair fat absorption and that thus reduce the absorption of vitamin K.
  • Disease or surgical interventions that affect the ability of the intestinal tract to absorb vitamin K, either through anatomic alterations or by changing the content of bile salts and pancreatic juices in the proximal small bowel, can result in significant reduction of vitamin K levels.
  • Chronic liver diseases such as primary biliary cirrhosis also deplete vitamin K stores.
  • Taking large amounts of mineral oil may reduce the absorption of vitamin K.
  • Inherited deficiency of the functional activity of the enzymes involved in vitamin K metabolism result in bleeding disorders.
  • Vitamin K deficiency in the newborn can be present for various reasons-

    • Maternal medications that interfere with vitamin K stores or function (eg, carbamazepine, phenytoin, barbiturates, some cephalosporins, rifampin, isoniazid, warfarin or warfarin like drugs) can result in vitamin K deficiency bleeding in the infant.
    • Transplacental transfer of vitamin K is very limited during pregnancy,
    • The storage of vitamin K in neonatal liver is also limited.
    • Breast milk is a poor source of vitamin K.
  • The other causes for late onset of vitamin K deficiency in infants include-
    • Diarrhea
    • Hepatitis
    • Cystic fibrosis
    • Celiac disease
    • Short bowel syndrome
    • Chronic exposure to broad spectrum antimicrobials

Pathophysiology

Newborn infants are at risk of developing vitamin K deficiency, and this coagulation abnormality leads to serious bleeding. This makes the newborn infant uniquely vulnerable to hemorrhagic disorders unless exogenous vitamin K is given for prevention of bleeding immediately after birth.

Once the infantile gut is colonized with bacterial flora,  the microbial production of vitamin K, results in a lower risk of infantile vitamin K deficiency bleeding. A gut-related microbial source of vitamin K is particularly important if dietary phylloquinone is restricted.

The most common sites of hemorrhage or bleeding are the umbilicus, mucus membrane, the GI tract, circumcision, and venipuncture sites. Hematomas frequently occur at the sites of trauma (ie, large cephalohematomas, scalp bruising related to instrumentation used at delivery, and, rarely, intracranial hemorrhage). Neonatal mortality and long-term neurologic morbidity are severe consequences of vitamin K deficiency bleeding.

Breast milk is a poor source of vitamin K (breast milk levels are 1-4 μ g/L). The recommended dietary intake of vitamin K is 1 μ g/kg/d. Exclusively breastfed infants have intestinal colonization with lactobacilli that do not synthesize vitamin K; thus, reduced production of menaquinones increases the neonatal risk of developing a hemorrhagic disorder if not supplemented with vitamin K. Formula-fed infants have higher fecal concentrations of vitamin K1 because of dietary intake and significant quantities of fecal menaquinones, reflecting the gut’s microflora.

Preterm infants who are receiving total parenteral nutrition (TPN) are not at risk because they are receiving vitamin K via the multivitamin additive to the TPN. Special consideration is needed for very low birth weight infants whose intestinal tract bacterial flora is altered because of multiple courses of broad-spectrum antimicrobials. Once preterm infants are weaned off of TPN, they may develop vitamin K deficiency if they are exclusively fed breast milk.

Frequency

The routine intramuscular administration of vitamin K immediately after birth has made vitamin K deficiency bleeding an uncommon occurrence.

Clinical Manifestations

  • The main symptom is bleeding (hemorrhage)—into the skin (causing bruises), from the nose, from a wound, in the stomach, or in the intestine.
  • Sometimes bleeding in the stomach causes vomiting with blood.
  • Blood may be seen in the urine or stool. In newborns, life-threatening bleeding within or around the brain may occur.
  • Having a liver disorder increases the risk of bleeding because proteins that help blood clot (clotting factors) are made in the liver.
  • Vitamin K deficiency may also weaken bones.
  • Most newborn infants are healthy upon examination, even if early onset bleeding is present; however, intracranial hemorrhage can occur during the delivery process and can lead to severe complications.
  • Internal hemorrhage of organs other than the brain may be difficult to detect; however, if they are suspected, careful physical monitoring and serial imaging after birth are indicated.
  • Soft tissue hemorrhages may be there.

Laboratory Studies

  • A Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen levels, and a platelet count should be included in the initial workup for vitamin K deficiency bleeding (VKDB) in a newborn.
  • A prolonged PT is usually the first laboratory test result to be abnormal in vitamin K deficiency bleeding due to reduction in Prothrombin, FVII, FIX, and FX levels.
  • A direct blood measurement of vitamin K is not useful because levels normally are low in newborns.
  • Infants with vitamin K deficiency bleeding typically have a prolonged PT with platelet counts and fibrinogen levels within the normal range for newborns.
  • Thrombocytopenia or a prolonged aPTT should prompt workup for other causes of bleeding during the neonatal period.
  • The diagnosis of vitamin K deficiency bleeding is confirmed if administration of vitamin K halts the bleeding and reduces the PT value.

Imaging Studies

  • MRI exposes the neonate to no radiation and is becoming the preferred way to study the brain because tissue damage can be better defined. 

Other Tests

  • A full coagulopathy work-up and hematology consultation are required if clinical and laboratory findings are suggestive of non–vitamin K deficiency bleeding.  
  • A work-up that includes functional tests and imaging are mandatory if liver disease is suspected. 
  • Hereditary defects in the coagulation system must always be considered among the differential diagnoses.

Treatment

A vitamin K injection in the muscle is recommended for all newborns to reduce the risk of bleeding within the brain after delivery. Otherwise, vitamin K is usually taken by mouth or given by injection under the skin. If a drug is the cause, the dose of the drug is adjusted or extra vitamin K is given. For patients with chronic malabsorption, 1–2 mg/d of vitamin K should be given orally, or 1–2 mg/week can be taken parenterally. Patients with liver disease may have an elevated prothrombin time because of liver cell destruction as well as vitamin K deficiency. If an elevated prothrombin time does not improve on vitamin K therapy, it can be deduced that it is not the result of vitamin K deficiency.

People who have vitamin K deficiency and a severe liver disorder may also need blood transfusions to replenish the clotting factors. A damaged liver may be unable to synthesize clotting factors even after vitamin K injections are given.

The reversal of excessive anticoagulant therapy with warfarin or warfarin-like drugs can be achieved by minimal doses of vitamin K (1 mg orally or by intravenous injection) for asymptomatic patients. This strategy can diminish the risk of bleeding while maintaining therapeutic anticoagulation for an underlying prothrombotic state.

Toxicity

Toxicity from dietary phylloquinone and menaquinones has not been described. High doses of vitamin K can impair the actions of oral anticoagulants.

Prevention

  • Intramuscular (IM) vitamin K prophylaxis at birth is the standard of care.
  • Commercial infant formulas contain supplemental vitamin K.
  • These measures have served to make vitamin K deficiency bleeding a rarity. However, parental refusal of prophylaxis and an increasing frequency of breastfeeding may cause a resurgence of vitamin K deficiency bleeding in developed countries.

Prognosis

  • In the absence of intracranial hemorrhage, the prognosis for vitamin K deficiency bleeding in an otherwise healthy infant is excellent.
  • Prognosis after intracranial hemorrhage depends on the extent and location of the hemorrhage.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Vitamin K represents a group of lipophilic and hydrophobic vitamins.

Chemistry

Three compounds have the biological activity of vitamin K, phylloquinone (Vitamin K1), the normal dietary source, found in green vegetables; menaquinones (vitamin K2), synthesized by intestinal bacteria, with differing lengths of side chain; and menadione and menadiol diacetate, synthetic compounds that can be metabolized to phylloquinone.

 Structure of vitamin K

Figure-1- Vitamin K family are naphtoquinone derivatives . Phylloquinones and menaquinones, both have a long isoprenoid side chain. The length of the side chain differs. Phylloquinonse have a  20 C side chain , whereas menaquinones have a 30 C side chain. The isoprenoid chain makes these vitamin hydrophobic or lipophilic. The synthetic vitamin K (menadione, menadiol diacetate) have only hydrogen in place of isoprenoid side chain that makes these vitamin water-soluble.

Menaquinones are absorbed to some extent, but it is not clear to what extent they are biologically active as it is possible to induce signs of vitamin K deficiency simply by feeding a phylloquinone-deficient diet, without inhibiting intestinal bacterial action.

Dietary Sources

Vitamin K is found in green leafy vegetables such as kale and spinach, and appreciable amounts are also present in margarine and liver. Vitamin K is present in vegetable oils and is particularly rich in olive, canola, and soybean oils.

Absorption and Storage

Absorption takes place in intestine in the presence of bile salts. The transportation from intestine is carried out through chylomicrons. Storage occurs in liver and from liver transportation to peripheral cells is carried out bound with beta lipoproteins.

Clinical significance

Fat malabsorption is associated with impaired absorption of vitamin K and other fat soluble vitamins. Vitamin K is important for the coagulation process. In its deficiency coagulation process is grossly affected resulting in tendency for bleeding and hemorrhages. Absorption of vitamin K may also be decreased by mineral oil, bile acid sequestrants (Cholestyramine, colestipol) and Orlistat (weight loss medication).

Recommended daily allowance

The average daily allowance is 50-100 mg/day.

Functions of vitamin K

Vitamin K Is the coenzyme for carboxylation of Glutamate in post synthetic modification of calcium binding proteins

The only known biological role of vitamin K is as a cofactor for an enzyme (Carboxylase) that catalyzes the carboxylation of the amino acid, glutamic acid, resulting in its conversion to gamma-carboxy glutamic acid (Gla). Although vitamin K-dependent gamma-carboxylation occurs only on specific glutamic acid residues in a small number of vitamin K-dependent proteins, it is critical to the calcium-binding function of those proteins.

Calcium binding proteins

Vitamin K–dependent proteins are a heterogeneous group, including clotting factor proteins and also proteins found in bone, lung, kidney, and placenta.

1) Role of vitamin K in coagulation

The ability to bind calcium ions (Ca2+) is acquired by the activation of the  vitamin K-dependent clotting factors, or proteins, in the coagulation cascade. Factors II (prothrombin), VII, IX, and X make up the core of the coagulation cascade. These factors are synthesized in the liver in the inactive form. They undergo post translational modifications, gamma carboxylation of glutamic acid residues. This process of  gamma carboxylation of glutamic acid residues imparts another negative charge, so as to promote the effective binding of these factors/proteins to calcium ions.

Vitamin K cycle

Although vitamin K is a fat-soluble vitamin, the body stores very little of it, and its stores are rapidly depleted without regular dietary intake. Perhaps, because of its limited ability to store vitamin K, the body recycles it through a process called the vitamin K cycle. The vitamin K cycle allows a small amount of vitamin K to function in the gamma-carboxylation of proteins many times, decreasing the dietary requirement.

Vitamin K hydroquinone (active form) is oxidized to the epoxide form during the process of enzymatic reaction.The initial form (hydroquinone form) is regenerated by two steps process. Vitamin K epoxide is reduced to the quinone by a epoxide reductase, and the quinone is reduced to the active hydroquinone by either the same reductase or by a vitamin K reductase(quinone reductase).(Figure-2)

 Vitamin K cycle

Figure-2-  Role of vitamin K in the gamma carboxylation of glutamate residues of various proteins. The arrow shows the site of action of warfarin. Reduced lipoamide is required for the activity of epoxide reductase whereas NADPH is needed for the action of vitamin K reductase.

Prothrombin and several other proteins of the blood clotting system (Factors VII, IX, and X, and proteins C and S) each contain 4–6 γ-carboxyglutamate residues. γ-Carboxyglutamate chelates calcium ions, and so permits the binding of the blood clotting proteins to membranes.

Vitamin K Antagonists

Some oral anticoagulants, such as Dicumarol and warfarin, inhibit coagulation through antagonism of the action of vitamin K. Warfarin prevents the recycling of vitamin K by inhibiting two important reactions and creating a functional vitamin K deficiency (figure-2).

Warfarin is a competitive inhibitor of epoxide reductase. In the presence of warfarin, vitamin K epoxides cannot be reduced, they accumulate and are excreted. As a result, abnormal precursor of prothrombin (preprothrombin) containing little or no carboxyglutamate, and incapable of chelating calcium, is released into the circulation. Thus, in the presence of warfarin or in vitamin K deficiency the process of coagulation is inhibited,

If enough vitamin K (as the quinone) is provided in the diet, it can be reduced to the active hydroquinone by the warfarin-insensitive enzyme (Vitamin K reductase) and carboxylation can continue, with stoichiometric utilization of vitamin K and excretion of the epoxide. Thus a high dose of vitamin K is the antidote to an overdose of warfarin.

Large quantities of dietary or supplemental vitamin K can overcome the anticoagulant effect of vitamin K antagonists, so patients taking these drugs are cautioned against consuming very large or highly variable quantities of vitamin K in their diets.

Like all anticoagulants, the major side effect of warfarin is bleeding. A rare complication is skin necrosis. Warfarin crosses the placenta and can cause fetal abnormalities. Treatment of pregnant women with warfarin can lead to fetal bone abnormalities (Fetal Warfarin syndrome). Consequently, warfarin should not be used during pregnancy.

 2) Vitamin K Is Also Important in Synthesis of Bone Calcium-Binding Proteins

Two proteins that contain γ-carboxyglutamate are present in bone, osteocalcin, and bone matrix Gla protein.

Osteocalcin is a protein synthesized by osteoblasts. The synthesis of osteocalcin by osteoblasts is regulated by the active form of vitamin D, 1,25(OH)2D3 or calcitriol. The mineral-binding capacity of osteocalcin requires vitamin K-dependent gamma-carboxylation of three glutamic acid residues. The function of osteocalcin is unclear but is thought to be related to bone mineralization. After gamma carboxylation osteocalcein binds tightly to calcium. Osteocalcin also contains hydroxyproline, so its synthesis is dependent on both vitamins K and C; in addition, its synthesis is induced by vitamin D. The release into the circulation of osteocalcin provides an index of vitamin D status.

Matrix Gla protein- MGP has been found in bone, cartilage, and soft tissue, including blood vessels. MGP prevents the calcification of soft tissues and cartilages, while facilitating normal bone growth and development.

Protein S- The vitamin K-dependent anticoagulant protein S is also synthesized by osteoblasts, but its role in bone metabolism is unclear. Children with inherited protein S deficiency suffer complications related to increased blood clotting as well as decreased bone density.

 

 

 Role of vitamin K (Summary)

Figure-3- vitamin K cycle and the role of vitamin K in post synthetic modification of calcium binding proteins.

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- Which vitamin deficiency is associated with sub acute combined degeneration of spinal cord?

Answer- Vitamin B12 deficiency is associated with sub acute combined degeneration of spinal cord. Peripheral nerves are usually affected first, and patients complain initially of paresthesias. The posterior columns next become impaired, and patients complain of difficulty with balance. In more advanced cases, cerebral function may be altered as well. An accumulation of Methylmalonyl-CoA in serum, has been suggested as a possible cause of neurologic defects seen in cobalamin deficiency by decreasing lipid synthesis.

Impaired biosynthesis of phosphatidyl choline due to decreased levels of methionine and S-adenosylmethionine (SAM) may also play a role in the neurologic symptoms of cobalamin deficiency by compromising the repair of demyelination.

Q.2- Which vitamin participates in the absorption of calcium from gut?

Answer- Vitamin D has an active role in the absorption of calcium from gut. Vitamin D promotes the synthesis of calbindin protein that promotes the absorption of calcium from gut. This action is brought about through nuclear receptors. it acts like a steroid hormone, binding to nuclear receptors and enhancing gene expression, although it also has rapid effects on calcium transporters in the intestinal mucosa

Q.3- A 2-year- old child presents with chronic cough, bronchitis, growth failure, chronic diarrhea and growth failure. A deficiency of which vitamin should be considered?

 Answer- The child is probably suffering from Vitamin A deficiency.

The child has chronic cough, bronchitis, growth failure and passage of light-colored, foul-smelling stools. All these symptoms are due to increased susceptibility to infections as a result of the keratinization of mucous membranes in the respiratory, GI, and urinary tracts. The thickened mucosa cracks easily and the risk for bacterial infections increases. During infection the synthesis of retinol binding protein is reduced in response to infection since it is a negative ‘Acute phase protein’, that results in decreased circulatory concentration of the vitamin with further deterioration of the immune system.

Q.4- A 2-year- old child has been brought to Pediatric O.P.D with the complaint of painful and difficult walking. General examination reveals bow legs and prominent costochondral junctions. Which vitamin supplementation should be given as a part of the treatment?

Answer- Vitamin D supplementation is needed as a part of treatment since the child seems to be suffering from Rickets. In young infants, rickets causes softening of the entire skull (Craniotabes). In older infants with rickets, sitting and crawling are delayed, as is Fontenelle closure; there is bossing of the skull and costochondral thickening. Costochondral thickening can look like bead like prominences along the lateral chest wall (rachitic rosary). In children 1 to 4 yr, epiphyseal cartilage at the lower ends of the radius, ulna, tibia, and fibula enlarge; Kyphoscoliosis develops, and walking is delayed. In older children and adolescents, walking is painful; in extreme cases, deformities such as bowlegs and knock-knees develop.

Q.5- Which vitamin deficiency is associated with Neural tube defects?

Answer- Neural tube defects are observed are due to maternal folic acid deficiency. Neural Tube Defects (NTDs) are birth defects of the brain and the spinal cord (malformations of the brain and spinal cord, causing anencephaly, spina bifida or encephalocele).It has been demonstrated that periconceptional (before and during the first 28 days after conception) supplementation of women with folic acid can decrease the risk of neural tube defects. Therefore, a daily intake of 400 µg folic acid in addition to a healthy diet 8 weeks prior to and during the first 12 weeks after conception is recommended. There is evidence that adequate folate status may also prevent the incidence of other birth defects, including cleft lip and palate, certain heart defects and limb malformations. To reduce the risk of neural tube defects, cereal grains are fortified with folate in some countries.

Q.6- Which vitamin deficiency is associated with egg white injury?

Answer- Raw egg whites contain Avidin, a glycoprotein that strongly binds to biotin and prevents its absorption. Thus, the ingestion of large quantities of raw egg white over a long period can result in a biotin deficiency.

Q.7- Name the coenzyme for the reaction for the conversion of Pyruvate to alanine.

Answer- Pyruvate to Alanine conversion is catalyzed by Transaminase (SGPT- Alanine transferase), that requires vitamin B6-P as a coenzyme.

Q.8- The bone marrow smear of a strict vegetarian female patient, presenting with weakness, fissured tongue and paralysis reveals megaloblastic anemia. Which vitamin deficiency is expected?

Answer- The patient is suffering from megaloblastic anemia. The cause seems to be B12 deficiency. Although it is synthesized exclusively by microorganisms, for practical purposes vitamin B12 is found only in foods of animal origin, there being no plant sources of this vitamin. This means that strict vegetarians (Vegans) are at risk of developing B12 deficiency.

Q.9- A 56 – year-old male on Isoniazid therapy for tuberculosis has developed rashes on the exposed parts of the body. What is the probable cause for these rashes?

Answer- The patient has developed pellagra. Prolonged treatment with the anti-tuberculosis drug, Isoniazid, can cause niacin deficiency. Isoniazid may induce a state of pyridoxine deficiency by combining with pyridoxine and generating inactive isoniazid-pyridoxal hydrazones, thus depleting the supply of pyridoxine. Pyridoxine is needed in the endogenous pathway of niacin synthesis. Thus diminished synthesis of niacin ultimately produces pellagra.

Q.10- Why is it said that babies undergoing phototherapy for physiological jaundice are prone to develop riboflavin deficiency?

Answer- Riboflavin is stable when heated and is not easily destroyed in the ordinary processes of cooking but it is light-sensitive so it is degraded easily by light, that is why infants undergoing phototherapy for jaundice  get prone to this deficiency. Loss of riboflavin is also seen if foods are left out in sunlight or in UV light. Because of this light sensitivity, riboflavin rapidly disappears from milk kept in glass bottles exposed to the sun or bright daylight (85% within 2 hours).

Q.11- A child from a very poor socio economic background has reported with loss of vision.Make a probable diagnosis. What is the underlying cause for blindness?

Answer- As the child is from a family with poor socio economic background, perhaps he is suffering from vitamin A deficiency.The earliest symptom of vitamin A deficiency is impaired dark adaptation, or night blindness. Severe deficiency causes xerophthalmia, ultimately resulting in corneal ulcers, scarring and blindness.

Q.12- What is the possible link between intake of polished rice and sudden cardiac failure?

Answer- The link between intake of polished rice and sudden cardiac failure is thiamine deficiency (wet beriberi).Polished rice or highly refined carbohydrates are poor sources of thiamine.

Thiamine deficiency is most commonly observed in chronic alcoholics or people subsisting on polished rice or high carbohydrate refined diets.

Q.13- Name an FMN dependent enzyme

Answer- L- amino acid oxidase that catalyzes the oxidative decarboxylation of amino acids requires the presence of FMN as a coenzyme.

Q.14- What are folate antagonists? Enlist a few clinically important Folate antagonists.

 Answer- Folate antagonists were originally developed as antileukemic agents, but are now being used and/or investigated in the treatment of a wide range of cancerous and non-cancerous diseases. Sulfanilamide and Trimethoprim are antibiotics, Pyrimethamine is antimalarial while Methotrexate is an anticancer drug.

Q.15- Cancer patients on Methotrexate therapy, develop Glossitis and oral ulcers, what is the possible reason?  

Answer- Methotrexate, an analog of 10-methyl-tetrahydrofolate, inhibits dihydrofolate reductase and has been exploited as an anti-cancer drug.  Methotrexate blocks the cell’s ability to regenerate THF, leading to inhibition of these biosynthetic pathways. The lack of nucleotides prevents DNA synthesis, and these cancer cells cannot divide without DNA synthesis.

Unfortunately, the effects of Methotrexate are nonspecific and other rapidly dividing cells such as epithelial cells in the oral cavity, intestine, skin, and blood cells are also inhibited. This leads to the side effects associated with methotrexate (and other cancer chemotherapy drugs) such as mouth sores, low white blood cell counts, stomach upset, hair loss, skin rashes, and itching.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- Name the vitamin that acts as a coenzyme for the post translational modifications of prothrombin.

Answer- The post translational modifications of prothrombin are carried out by gamma carboxylation of its glutamic acid residues. The reaction is catalyzed by carboxylase enzyme  which requires vitamin K as a coenzyme. CO 2 and O2 are also required for this carboxylation process.The ability to bind calcium ions (Ca2+) is required for the activation of the seven vitamin K-dependent clotting factors, or proteins, in the coagulation cascade. Vitamin K-dependent gamma-carboxylation of specific glutamic acid residues in those proteins makes it possible for them to bind calcium.

Q.2- Treatment of pregnant women with warfarin can lead to fetal bone abnormalities (fetal warfarin syndrome), what is the cause for this disorder?

Answer-  Warfarin is a vitamin K antagonist; its mechanism of action involves inhibition of vitamin K cycle producing vitamin K deficiency.The fetus gets the supply of vitamin K from maternal circulation as there are no other sources, so the maternal vitamin K deficiency results in fetal deficiency. There is gross impairment of gamma carboxylation of fetal vitamin K dependent proteins. Under carboxylation adversely affects the capacity to bind the bone mineral that is the reason for the malformed bones.

Q.3- Vitamin B6 deficiency leads to niacin deficiency also, suggest the reason for it.

Answer- vitamin B6 is required as a coenzyme for the enzyme kynureninase, which is an enzyme of the pathway of biosynthesis of niacin from tryptophan. In B6 deficiency, niacin is inappropriately synthesized,B6 being unavailable at the Kynureninase step, hence niacin deficiency also sets in and clinical manifestations of deficiencies of both vitamins are observed..

Q.4- Name a water-soluble vitamin that is required for the synthesis of collagen.

Answer- Vitamin C is required for the synthesis of collagen. The enzymes Prolyl and lysyl hydroxylases require vitamin C for their actions to form hydroxy proline and hydroxy lysine from proline and lysine  respectively. These post translational modifications are required for the formation of triple helical structure of collagen. Deficiency of vitamin C leads to impaired hydroxylation reactions with the resultant formation of a weak collagen.

Q.5- What is the cause of hyperkeratinization in vitamin A deficiency?

Answer- Vitamin A (Retinoic acid) regulates the synthesis of keratin by regulating its gene expression. In vitamin A deficiency keratin is excessively synthesized resulting in hyperkeratinization of mucus membranes which can easily crack to allow bacterial invasion with the resultant increased frequency of infections in vitamin A deficiency. Since vitamin A decreases the expression of keratin gene, vitamin A is given therapeutically for the treatment of acne.

Q.6- What is the absorbable form of Thiamine?

Answer- Thiamine occurs in the human body as free thiamine and in various phosphorylated forms: thiamine monophosphate (TMP), thiamine triphosphate (TTP), and thiamine pyrophosphate (TPP), which is also known as thiamine diphosphate. Thiamine pyro phosphate is the active form of Thiamine. It is rapidly converted to its active form, in the brain and liver by a specific enzyme, TPP synthetase. The synthesis of TPP from free thiamine also requires the presence of magnesium and adenosine triphosphate (ATP).

Q.7- Name the active form/forms of Riboflavin.

Answer- Riboflavin (B2) exists in two active forms FMN (flavin mono nucleotide) and FAD (flavin adenine dinucleotide). In the body, riboflavin occurs primarily as an integral component of the enzymes. These coenzymes participate in a large majority of the reactions in the body.

Q.8- Which forms of Cobalamine is required for the methylation of Homocysteine to Methionine ?

Answer- Methyl Cobalamine form is required for the methylation of homocysteine to Methionine.

Q.9- Which vitamin deficiency is associated with lactic acidosis?

Answer-  Lactate, a product of anaerobic glucose metabolism, is generated from pyruvate with lactate dehydrogenase as a catalyst. Pyruvate is normally aerobically metabolized to CO2 and H2O in the mitochondrion. Initially pyruvate is converted to Acetyl co A with pyruvate dehydrogenase complex acting as a catalyst requiring thiamine, niacin, riboflavin, pantothenic acid and lipoic acid as coenzymes. Acetyl co A is completely oxidized in the Krebs cycle.

Normally, pyruvate is in a state of equilibrium with lactate and under condition like thiamine deficiency, when PDH complex becomes less active, the equilibrium is shifted towards production of lactate. Lactate is cleared from blood, primarily by the liver, with the kidneys (10-20%) and skeletal muscles to a lesser degree. Lactic acidosis results from an increase in blood lactate levels when lactate production exceeds consumption and body buffer systems become overburdened.

Q.10- Which vitamin supplementation is given to treat morning sickness of pregnancy?

Answer- B6 is given to treat morning sickness of pregnancy. It is also given to treat radiation sickness, muscular dystrophies and epileptiform convulsions.

Q.11- Total non vegetarian diet can produce scurvy, is it true or false?

Answer-  It is true. Vitamin C is mainly present in citrus fruits and green leafy vegetables. Hence a pure non vegetarian diet can precipitate vitamin C deficiency.

Q.12- Name the enzyme required for the conversion of carotene to Retinal.

Answer- Carotene-β- dioxygenase catalyzes the conversion of beta carotene to form retinal. The conversion is inefficient and also Beta carotene has 1/6th activity as that of retinol. Due to this reason, excess carrots ingestion(carrots are rich in beta carotene) does not lead to vitamin A toxicity.

Q.13- What are the clinical manifestations of B12 deficiency?

Answer- The hallmark of symptomatic vitamin B12 deficiency is megaloblastic anemia. The megaloblastic state also produces changes in mucosal cells, leading to glossitis, as well as other vague gastrointestinal disturbances such as anorexia and diarrhea. Cobalamine deficiency also can present with numerous neurologic manifestations including: numbness, paresthesias, weakness, ataxia, abnormal reflexes and diminished vibratory sensation.

Q.14- For which defect in the body, Schilling test is carried out?

Answer- Scilling test is carried out for the diagnosis of pernicious anemia. The Schilling test can determine if the deficiency is due to absence of intrinsic factor, or some malabsorption disorder. The Schilling test measures Cbl (cobalamine)absorption by increasing urine radioactivity after an oral dose of radioactive Cbl.

Q.15- Which vitamin deficiency is detected by intradermal dye test?

Answer- Vitamin C deficiency is detected by intradermal dye test. Intradermal injections of 2,6-dichlorophenol indophenol are given and the time is noted for the decolorization of the injected area. The dye is expected to be reduced by vitamin C and upon reduction the dye becomes colorless. Abnormally long persistence of blue color in cutaneous wheal indicates sub saturation of vitamin C (vitamin C deficiency).

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- Which type of Transcobalamine is required for the transportation of vitamin B12?

Answer- Three plasma transport proteins have been identified. Transcobalamine I and III (differing only in carbohydrate structure) are secreted by white blood cells. Although approximately 90% of plasma vitamin B12 circulates bind to these proteins, only Transcobalamine II is capable of transporting vitamin B12 into cells.

Q.2- Name any two inhibitors of conjugase enzyme, that is required for the removal of extra Glutamic acid residues from the dietary folic acid?

Answer- Conjugase (γ-glutamyl carboxypeptidase) in the intestinal lumen cleaves off extra Glutamic acid residues, and folate is absorbed by the mucosa of the small intestine. Alcohol and Anticonvulsant drugs, such as Dilantin, interfere with mucosal conjugase, hence impair folate absorption.

Q.3- Which form of folic acid is required for the de novo synthesis of purine nucleotide?

Answer- Two different forms of folate are required for different aspects of nucleotide biosynthesis. N10-formyl THF provides the C-2 and C-8 carbons for the de novo synthesis of purine rings, and thus is critical for DNA metabolism. The Methylene form, N5,N10-methylene THF, is required for the production of dTMP from dUMP (pyrimidine nucleotide) .

Q.4- Which form of vitamin B12 is present in plasma ?

Answer- Cobalamin (vitamin B12) exists in a number of different chemical forms. All have a cobalt atom at the center of a corrin ring. In nature, the vitamin is mainly in the 2-deoxyadenosyl (ado) form, which is located in mitochondria. It is the cofactor for the enzyme Methylmalonyl CoA mutase. The other major natural cobalamin is methylcobalamin, the form in human plasma and in cell cytoplasm. It is the cofactor for methionine synthase. There are also minor amounts of hydroxocobalamin to which methyl- and Adenosyl cobalamin are rapidly converted by exposure to light.

Q.5- Why is it said that the requirement of riboflavin increases with the increasing protein load ?

Answer-Riboflavin is required for the catabolism especially the  oxidative deamination of amino acids. Thus its requirement increases with the increasing protein load.

Q.6- Why is it said that the maize eaters must supplement with niacin ?

Answer- Maize lacks tryptophan which is a precursor of niacin in the body (60 mg of tryptophan is required for the synthesis of 1 mg of niacin). Maize does contain niacin but it is present in the bound form and is thus not available for biological use. Thus Maize eaters  generally manifest pellagra like rashes due to underlying niacin deficiency.

Q.7-What is the basis of using B6-P as a drug for treating infantile convulsions?

Answer- B6-P is required for the decarboxylation of amino acids. Glutamic acid undergoes decarboxylation under the activity of decarboxylase enzyme in the presence of B6-P to form GABA (gamma amino butyric acid) which is an inhibitory neurotransmitter. Thus there is relief of convulsions which is a state of hyper excitation, by B6P through promoting the synthesis of GABA.

Q.8-Which vitamin is required for the absorption of amino acids from the gut?

 Answer- Vitamin B6 is required for the active absorption of amino acids from the gut.

Q.9- Which vitamin is required as coenzyme for the activity of lactate dehydrogenase enzyme?

Answer- Lactate dehydrogenase catalyzes the interconversion of pyruvate and lactate. Niacin in the form of NAD+ is required as a coenzyme for the activity of lactate dehydrogenase enzyme.

Q.10-Name the enzyme catalyzing the activation of vitamin B6

Answer- Pyridoxal kinase catalyzes the conversion of B6 to B6-P, the metabolically active form of Vitamin B6.

Q.11- Name the synthetic form of vitamin K.

Answer- Three compounds have the biological activity of vitamin K phylloquinone, the normal dietary source, found in green vegetables; menaquinones, synthesized by intestinal bacteria, with differing lengths of side chain; and menadione and menadiol diacetate, synthetic compounds that can be metabolized to phylloquinone.

Q.12- Achlorhydria can precipitate the deficiency of Vitamin B12,  is it true?

Answer- Intrinsic factor (IF) is required for the absorption of vitamin B12 which is secreted by the parietal cells of stomach, In conditions of gastric atrophy due to genetic causes or auto immune destruction, apart from HCl , intrinsic factor is also not synthesized with the resultant impaired absorption of vitamin B12 and pernicious anemia as a consequence.

Q.13- Name the inhibitors of vitamin K that act as anticoagulants.

Answer- Although vitamin K is a fat-soluble vitamin, the body stores very little of it, and its stores are rapidly depleted without regular dietary intake . The oral anticoagulants, such as Dicumarol and warfarin, inhibit coagulation through antagonism of the action of vitamin K.

Q.14-The synthesis of which vitamin is inhibited by Sulphonamides?

Answer- The synthesis of folic acid is inhibited by sulphonamides (sulphanilamides).  Because its shape is similar to that of p-aminobenzoic acid, sulfanilamide inhibits the growth of bacteria by interfering with their ability to use p-aminobenzoic acid to synthesize folic acid. Sulfa drugs were the first antimetabolites to be used in the treatment of infectious disease. Because humans don’t make folic acid, sulfanilamide is not toxic to humans in the doses that inhibit bacteria. This ability to inhibit bacteria while sparing humans made them useful in preventing or treating various infections.

Q.15- Which form of vitamin A -11 cis Retinal or 11-cis Retinol is required for vision?

Answer- Vitamin A, in the strictest sense, refers to retinol. However, the oxidized metabolites, retinaldehyde and retinoic acid, are also biologically active compounds. The term retinoids includes all molecules (including synthetic molecules) that are chemically related to retinol. Retinaldehyde (11-cis) is the essential form of vitamin A that is required for normal vision, whereas retinoic acid is necessary for normal morphogenesis, growth, and cell differentiation.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

 Q.1- Which vitamin deficiency affects the synthesis of carnitine in the muscle?

Answer- Vitamin C is required for the synthesis of carnitine. Carnitine ( β hydroxy-γ-trimethyl ammonium butyrate), (CH3)3N+—CH2—CH(OH)—CH2—COO, is widely distributed and is particularly abundant in muscle. Carnitine facilitates the beta-oxidation of fatty acids, through its role in transporting long chain fatty acids from the cytoplasm into the mitochondrial matrix of cardiac and skeletal muscle. Vitamin C dependent trimethyllysine and -γ butyrobetaine hydroxylases are required for the synthesis of carnitine. Vitamin C acts as a reducing agent in these reactions.

Q.2- Why is it said that Niacin and vitamin D are not true vitamins?

Answer- The distinguishing feature of the vitamins is that they generally cannot be synthesized by mammalian cells and, therefore, must be supplied in the diet.Vitamin D, which is formed in the skin after exposure to sunlight, and niacin, which can be formed from the essential amino acid tryptophan, do not strictly comply with this definition. However, the ability to utilize tryptophan for niacin synthesis is inefficient (60 mg of tryptophan are required to synthesize 1 mg of niacin).

Q.3- What is the cause of bleeding tendencies in obstructive jaundice?

Answer- In obstructive jaundice there is obstruction to the outflow of bile. Bile salts are needed for the absorption of fat soluble vitamins. Vitamin K, a fat soluble vitamin has an active role in coagulation of blood. In conditions of malabsorption or obstructive jaundice, Vitamin K deficiency sets in with the resultant impaired coagulation of blood and bleeding tendencies.

Q.4- Which form of vitamin B2 (Riboflavin) is required for the activity of succinate dehydrogenase enzyme of TCA cycle ?

Answer- Succinate dehydrogenase catalyzes the conversion of succinate to fumarate; FAD form of vitamin B2 is required as a coenzyme for this reaction.

Q.5- Which vitamin is required for the activity of muscle glycogen phosphorylase enzyme?

Answer- B6-P is required for the activity of muscle glycogen phosphorylase enzyme. Approximately 80% of the body’s total vitamin B6 is present in muscle, mostly associated with glycogen phosphorylase. This is not available in deficiency, but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids.

Q.6-  Which vitamin is required in higher amount with increasing carbohydrate load?

Answer- The requirement of thiamine increases with heavy carbohydrate diet. Because thiamine is required for enzymes involved in glucose metabolism such as Pyruvate dehydrogenase complex, Alpha keto glutarate dehydrogenase complex and transketolase, so its requirement also increases with the increasing carbohydrate load for the proper functioning of these enzymes. The severe thiamine deficiency disease known as Beriberi is the result of a diet that is carbohydrate rich and thiamine deficient. In subjects on a relatively high carbohydrate diet, this results in increased plasma concentrations of lactate and pyruvate which may cause life-threatening lactic acidosis.

Q.7- Which vitamin is required for the synthesis of Sphingol required for the formation of sphingomyelin?

Answer- Vitamin B6-P is required for the formation of Sphingol (an amino alcohol) required for the synthesis of sphingomyelins (Sphingophospholipids).

Q.8- Name a vitamin required for as a coenzyme for the activity of SGOT?

Answer- SGOT- Serum Glutamate Oxalo acetate transaminase is B6-P dependent and catalyzes the reversible transamination reaction involving glutamate and oxaloacetate for the formation of aspartate and alpha ketoglutarate.

Q.9-Name a vitamin required for the activity of dihydrofolate reductase?

Answer- Dihydrofolate reductase as the name indicates is associated with folic acid and catalyzes the conversion of dihydrofolate to Tetrahydrofolate (active form). Methotrexate acts as a competitive inhibitor of this enzyme and is used as an anticancer drug.

Q.10- Name a vitamin, the deficiency of which is detected by Reduced Red cell Glutathione reductase activity.

Answer- The deficiency of vitamin B2 is detected by estimating RBC Glutathione reductase enzyme.

Q.11- What should be the clinical outcome if Riboflavin deficiency is detected?

Answer- Most prominent effects are seen on the skin, mucosa and eyes: Glossitis (magenta tongue, geographical tongue), cheilosis, angular stomatitis (fissures at the corners of the mouth), sore throat, burning of the lips, mouth, and tongue ,inflamed mucous membranes, pruritus (itching) and seborrheic dermatitis (moist scaly skin inflammation) are the symptoms commonly observed in deficient individuals.

Q.12- Name a vitamin/ Vitamins required for the activity of Pyruvate dehydrogenase complex.

Answer- Pyruvate dehydrogenase, a multienzyme complex, catalyzes the oxidative decarboxylation of pyruvate to form Acetyl co A. It requires Thiamine pyrophosphate (TPP), pantothenic acid, lipoic acid, riboflavin and niacin for it’s activity. The deficiency of any of these vitamins can affect the activity of this enzyme complex. Most common out of these is thiamine deficiency.

Q.13- Name the vitamin that is required as a coenzyme for the conversion of Acetyl co A to Malonyl co A?

Answer- The conversion of Acetyl co A to malonyl co A , the first step of fatty acid synthesis, is catalyzed by Acetyl co A carboxylase enzyme, that requires biotin as a cofactor. It is a carboxylation reaction.

Q.14- Which enzyme is inhibited by Dicoumarol and what is the mode of inhibition?

Answer- Dicoumarol acts as an anti coagulant. It is a competitive inhibitor of Epoxide reductase, the enzyme that catalyzes the conversion of epoxide form of vitamin K to quinone form. Quinone form is further reduced to hydroquinone form (functional form) that can be further utilized for gamma carboxylation of glutamic acid residues. In the presence of dicoumarol, the functional form of vitamin K is not regenerated and hence coagulation cascade is not triggered.

Q.15- Which vitamin/vitamins participate in the synthesis of catecholamines?

Answer- Vitamin C and B6 are required for the synthesis of catecholamines. B6 is required for the decarboxylation and vitamin C is required for the hydroxylation reactions.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1- Name two vitamin B-6 Phosphate dependent enzymes.

Answer- Vitamin B6 serves as a coenzyme of approximately 100 enzymes that catalyze essential chemical reactions in the human body. It plays an important role in protein, carbohydrate and lipid metabolism. Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially transamination, deamination and decarboxylation reactions. It is also the cofactor of glycogen phosphorylase.

2- Which out of the two oxidases, L-Amino acid Oxidase or D- amino acid Oxidase, require FMN as a prosthetic group?

Answer- L-amino acid oxidases require FMN while FAD is required by D- Amino acid oxidases.

3- What is the cause for neurological manifestations in B6P deficiency?

Answer- It is required for the synthesis of neurotransmitters like Serotonin, GABA (Gamma amino butyric acid) and also Dopamine, norepinephrine and epinephrine . These are produced by decarboxylation reactions .B6-P is also required for the synthesis of sphingomyelins and other sphingolipids that are required for the formation of myelin sheath. Therefore deficiency of B6-P results in impairment of such reactions and hence neurological deficit.

4- What are the different forms in which the disease Beriberi can be manifested ?

Answer- Beriberi is the outcome of vitamin B1(thiamine) deficiency. It is manifested as dry, wet, infantile, cerebral (Wernicke’s Korsakoff syndrome) or shoshin beriberi.

5- Which vitamin deficiency, B6 or B12 is associated with Homocystinuria?

Answer- Homocystinuria is associated with deficiencies of both B6 and B12. It is also associated with folic acid deficiency. The remethylation of homocysteine back to methionine is B12 and folic acid dependent, (Homocystine is a dimer), while further metabolism of homocysteine is B6 dependent. Thus deficiency of any of these vitamins can cause accumulation of homocysteine in blood and also excessive excretion in urine (dimeric form).

6- Which vitamin is required for the synthesis of bile salts from cholesterol?

Answer- Vitamin C (ascorbic acid) is required for the activity of 7-α hydroxylase, the key regulatory enzyme of bile acid synthesis from cholesterol. Bile salts are produced from bile acids.

7- Name the vitamin required as a coenzyme for the conversion of Pyruvate to Oxaloacetate?

Answer- Biotin is required as a coenzyme, since it is a carboxylation reaction catalyzed by pyruvate carboxylase enzyme. This is the first step of gluconeogenesis.

8- What is the cause of reduced RBC Transketolase activity in Thiamine deficiency?

Answer- Transketolase enzyme is the enzyme of HMP pathway, a pathway of glucose utilization. Thiamine as TPP (active form- Thiamine pyrophosphate form) is required as a coenzyme for the functioning of this enzyme. In thiamine deficiency, the activity of this enzyme goes down and that is estimated in red blood cells to diagnose the underlying deficiency.

9- Why are alcoholics more prone to Thiamine deficiency?

Answer- Reduced dietary intake and  impaired absorption are the important causes of thiamine deficiency in chronic alcoholics.

10- Which vitamin deficiency can be detected by Tryptophan load test?

Answer- Tryptophan load test is undertaken to diagnose underlying B6-P deficiency. Tryptophan is given as a loading dose and the amount of xanthurenic acid excreted in urine is estimated. In B6 deficiency, the amount of xanthurenic acid excreted in urine is increased (Xanthurenic acid is normally produced in a very small amount, but it is produced in excess in B6 deficiency.)

11- Which water soluble vitamin participates in the transfer of one carbon fragments?

Answer- Folic acid is the carrier of one carbon fragments. Tetrahydrofolate can carry one-carbon fragments attached to N-5 (formyl, formimino, or methyl groups), N-10 (formyl) or bridging N-5–N-10 (methylene or methenyl groups).

12-Which vitamin participates in decarboxylation reactions of amino acids?

Answer- Decarboxylation reactions  of amino acids are catalyzed by decarboxylases that require B6 as a coenzyme. The neurotransmitters serotonin, GABA, Dopamine, norepinephrine and epinephrine are produced by decarboxylation of amino acids.

13- Which vitamin deficiency leads to impaired coagulation of blood?

Answer- Vitamin K is required for coagulation of blood. Vitamin K deficiency is the cause of bleeding tendencies and impaired coagulation of blood.

14- What is the basis of supplementation with Folic acid, B12 and B6 to prevent IHD?

Answer- Folic acid, B12 and B6 participate in the metabolism of homocysteine. Excess of homocysteine has atherogenic effect and increases the tendency for ischemic heart disease in the high risk people or people having family history of IHD. Deficiency of any of these vitamins can cause accumulation of homocysteine in blood, thus as a precaution these vitamins are supplemented to prevent the trigger of atherosclerosis by hyperhomocysteinemia.

15- What are the toxic effects of high dose niacin therapy?

Answer- Prostaglandin-mediated flushing due to binding of the vitamin to a G protein–coupled receptor has been observed at daily doses as low as 50 mg of niacin when taken as a supplement or as therapy for dyslipidemia. It may be more intense after alcohol ingestion, aerobic activity, sun exposure, and consumption of spicy foods.  There is no evidence of toxicity from niacin derived from food sources. Flushing always starts in the face and may be accompanied by skin dryness, itching, paresthesias, and headache. Premedication with aspirin may alleviate these symptoms. Nausea, vomiting, and abdominal pain also occur at similar doses of niacin. Hepatic toxicity is the most serious toxic reaction due to niacin and may present as jaundice.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1- What is the expected clinical outcome of niacin deficiency ?

Answer- Niacin deficiency in severe form is manifested as Pellagra. Disoriented memory (dementia), diarrhea and dermatitis are the signs of pellagra. In untreated cases it leads to death (4 Ds)

2- Why should milk be preferably stored in dark bottles?

Answer- Riboflavin (B1) present in milk is photosensitive, it is destroyed upon exposure to light. Hence to avoid, milk should be stored in dark bottles.

3- Why are premature infants given vitamin K injections immediately after birth?

Answer- Newborn infants, in general, have low vitamin K status for the following reasons:

a) Vitamin K is not easily transported across the placental barrier;

b) The newborn’s intestines are not yet colonized with bacteria that synthesize menaquinones; and

c) The vitamin K cycle may not be fully functional in newborns, especially premature infants.

4- The patients suffering from Carcinoid syndrome generally manifest pellagra like rashes, what could be the reason for this?

Answer- In carcinoid syndrome, tryptophan metabolism is diverted towards serotonin production and less is available for the synthesis of niacin. Niacin deficiency is thus manifested as dementia, dermatitis and diarrhea (pellagra).

5- Which vitamin deficiency is associated with Methyl malonic aciduria?

Answer- Vitamin B12 deficiency is required as a coenzyme for the activity of methyl malonyl co A mutase enzyme that catalyzes the conversion of L-Methyl malonyl co A to Succinyl co A. In vitamin B12 deficiency this conversion is impaired with the resultant excessive accumulation of methyl malonic acid in serum as well as excretion in urine.

6- Which Carboxylation reaction does not require Biotin for its activity?

Answer- Generally biotin is required as a coenzyme for the carboxylation reactions , but gamma carboxylation of specific glutamic acid residues in certain proteins is vitamin K dependent, as in factor II, VII, IX and X of coagulation cascade and osteocalcein (calcium binding proteins).

7- Name two TPP dependent enzymes.

Answer- TPP (Thiamine pyro phosphate), the active form of thiamine is required as a coenzyme for enzymes such as Pyruvate dehydrogenase, Alpha-ketoglutarate dehydrogenase, and branched chain keto acids (BCKA) dehydrogenase complexes and Transketolase.

8- Which vitamin deficiency is associated with Sideroblastic anemia?

Answer- Vitamin B6 deficiency is associated with sideroblastic anemia as it is required as a coenzyme in the pathway of heme biosynthesis (for ALA synthase enzyme).Deficiency leads to impaired heme synthesis and thus reduced Hb synthesis. Deranged heme synthesis in the developing red cell leads to decreased hemoglobin production with the formation of hypochromic and microcytic red cells and other misshaped erythrocytes. These red cells are the progeny of the ring sideroblasts that constitute the diagnostic hallmark of any sideroblastic anemia. 

9 – Which vitamin is known to participate in Carnitine synthesis?

Answer- Vitamin C is required for the synthesis of carnitine. Carnitine is required for the transportation of fatty acid across the inner mitochondrial membrane in to the mitochondrial matrix where the oxidation of fatty acids takes place.

10 – Name the antioxidant vitamins.

Answer-An antioxidant is a substance that significantly decreases the harmful effects of “reactive species”, such as reactive oxygen and nitrogen molecules that disrupt normal physiological function on a cellular level in humans. Examples include the antioxidant vitamin C, vitamin E, and the carotenoids (vitamin A). Selenium is also an antioxidant.  A multitude of other nutrients, including minerals such as copper, manganese, and zinc, flavonoids, and coenzyme Q10, also possess antioxidant properties.

11- What are the clinical findings in a case of Rickets?

Answer- Rickets is caused by a failure of osteoid to calcify in growing children. It occurs due to vitamin D deficiency.  The clinical manifestations include-frontal bossing,bow legs, knock-knees, rachitic rosary along the costochondral junctions, Harrison groove and in more severe instances in children older than 2 years, vertebral softening leading to Kyphoscoliosis. In the long bones, laying down of uncalcified osteoid at the metaphysis leads to spreading of those areas, producing knobby deformity.

12- What are the target organs /tissues for the action of vitamin D ?

Answer- The target organs for vitamin D are bone, intestine and kidney. The basic function of vitamin D is to promote the reabsorption of calcium so as to maintain the serum calcium levels and to promote the mineralization of bones.

13- Which vitamin is known to participate in the oxidative deamination reactions of amino acids?

Answer- Riboflavin is required for the oxidative deamination reactions. FMN form is required for L-amino acid oxidases while FAD is required for D-amino acid oxidases.

14- Which water soluble vitamin is stored in liver ?

Answer- Vitamin B12 is the only water soluble vitamin that is stored in the body (in the liver). The liver contains 2000–5000 mcg of stored vitamin B12. Since daily losses are 3–5 mcg/d, the body usually has sufficient stores of vitamin B12 so that vitamin B12 deficiency develops more than 3 years after vitamin B12 absorption ceases.

15- Why is vitamin D considered a hormone?

Answer- Vitamin D is actually a hormone since its mechanism of action resembles that of hormones. Like hormones it is required only in small amount. Most if not all actions of vitamin D are mediated through a nuclear transcription factor known as the vitamin D receptor (VDR) similar to hormones.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1- A homeless person has been brought to emergency. Blood biochemistry reveals highf lactate levels. An impaired activity of PDH complex is suspected. Which vitamin deficiency can cause such symptoms ?

Answer- It is a case of thiamine (B1) deficiency. PDH complex catalyzes the conversion of Pyruvate to Acetyl co A . The multienzyme complex requires the presence of thiamine, lipoic acid, pantothenic acid, riboflavin and niacin. A deficiency of thiamine (TPP- active form) which is very common in alcoholics usually presents with lactic acidosis. Due to impaired activity of PDH complex alternatively pyruvate is converted to lactate causing lactic acidosis.

2. A 22-year-old female has presented with seborrheic dermatitis. Blood biochemistry reveals reduced activity of Glutathione reductase enzyme. Which vitamin deficiency is suspected in this patient ?

Answer- It is a case of Riboflavin (B2) deficiency.  Riboflavin is essential for healthy skin, nails, hair growth and general good health. Characteristic symptoms of riboflavin deficiency include lesions of the skin, especially in the corners of the mouth, and a red, sore tongue. Assessment of Riboflavin status can be done by erythrocyte glutathione reductase activity.

3.What would be the clinical outcome if vitamin C is deficient?

Answer- Vitamin C deficiency can occur as part of general under nutrition, but severe deficiency (causing scurvy) is uncommon. Symptoms include fatigue, depression, and connective tissue defects (eg, gingivitis, petechiae, rash, internal bleeding, impaired wound healing). In infants and children, bone growth may be impaired. Severe deficiency results in scurvy, a disorder characterized by hemorrhagic manifestations and abnormal osteoid and dentin formation. Diagnosis is usually clinical. Treatment consists of oral vitamin C

4.- Name a confirmatory test to diagnose underlying Thiamine deficiency.

Answer- R.B.C Transketolase activity and 24-h urinary thiamine excretion may be measured  to diagnose underlying thiamine deficiency.

5 – Which vitamin is known to participate in the Carboxylation reactions?

Answer- Biotin participates in the carboxylation reactions. The enzymes like Pyruvate carboxylase, Acetyl  co A carboxylase and Propionyl co A carboxylase require Biotin as a coenzyme. These carboxylation reactions require CO2 and ATP as a source of energy.

6- What is the active form of vitamin B6?

Answer- Vitamin B6, also called pyridoxine is active in the pyridoxal-phosphate form. There are six forms of vitamin B6: pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM), and their phosphate derivatives: pyridoxal 5′-phosphate (PLP), pyridoxine 5′-phosphate (PNP), and pridoxamine 5′-phospate (PNP). PLP is the active coenzyme form, and has the most importance in human metabolism.

7- Which vitamin deficiency is associated with Burning feet syndrome?

Answer- Mostly deficiency of Pantothenic acid is associated with burning feet syndrome.

8- Name a folate antagonist used as an anticancer drug.

Answer- Methotrexate , a folate antagonist is used as an anticancer drug. Methotrexate, an analog of 10-methyl-tetrahydrofolate, inhibits dihydrofolate reductase and has been exploited as an anti-cancer drug. Methotrexate blocks the cell’s ability to regenerate THF, leading to inhibition of these biosynthetic pathways.The lack of nucleotides prevents DNA synthesis, and these cancer cells cannot divide without DNA synthesis.

9-Which vitamin is known to participate in the hydroxylation reactions?

Answer- Vitamin C, also known as ascorbic acid participates in the hydroxylation reactions. Vitamin C  is the coenzyme for two groups of hydroxylases. These are copper-containing hydroxylases and the α -ketoglutarate-linked iron-containing hydroxylases.

10-Name the vitamins, the deficiencies of which can be manifested as megaloblastic anemia.

Answer- Both folate and cobalamine deficiencies have similar megaloblastic  anemia and GI symptoms. However, cobalamine deficiency also can present with numerous neurologic manifestations including: numbness, paresthesias, weakness, ataxia, abnormal reflexes and diminished vibratory sensation.

11- Which vitamin deficiency would be precipitated by a complete vegetarian diet?

Answer- Since vitamin B12 is present in all foods of animal origin, dietary vitamin B12 deficiency is extremely rare and is seen only in vegans—strict vegetarians who avoid all dairy products as well as meat and fish

12- Which vitamin deficiency would be precipitated by a complete non vegetarian diet?

Answer- Folic acid and vitamin C deficiencies are expected in persons with a complete non vegetarian dietary pattern  as these vitamins are mostly of plant origin.

13- New born infants exposed to blue light for phototherapy generally develop Riboflavin deficiency, suggest the reason for it.

Answer- Riboflavin is sensitive to light and becomes inactive upon exposure that is why deficiency is precipitated.

14- Which vitamin deficiency is known to cause bleeding gums?

Answer- Vitamin C deficiency causes bleeding gums. Gums may become swollen, purple, spongy, and friable; they bleed easily in severe deficiency.

15- Name a vitamin which is used therapeutically as a lipid lowering drug

Answer- Niacin reduces plasma triglyceride and LDLc levels and raises the plasma concentration of HDLc. Niacin is also the only currently available lipid-lowering drug that significantly reduces plasma levels of Lp (a). If properly prescribed and monitored, niacin is a safe and effective lipid-lowering agent.

 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

http://www.slideshare.net/namarta28/thiamine

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- Discuss the steps of activation of vitamin D, and explain the reason for the fact that Vitamin D is toxic in excess, but excessive exposure to sunlight does not lead to vitamin D toxicity.

Answer- Vitamin D3 (cholecalciferol) can be synthesized by humans in the skin upon exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be obtained from the diet. When exposure to UVB radiation is insufficient for the synthesis of adequate amounts of vitamin D3 in the skin, adequate intake of vitamin D from the diet is essential for health. Plants synthesize ergosterol, which is converted to vitamin D2 (Ergocalciferol) by ultraviolet light.

In response to ultraviolet radiation of the skin, a photochemical cleavage results in the formation of vitamin D from 7-dehydrocholesterol. Cutaneous production of vitamin D is decreased by melanin and high solar protection factor sunblocks, which effectively impair skin penetration of ultraviolet light. The increased use of sunblocks in North America and Western Europe and a reduction in the magnitude of solar exposure of the general population over the past several decades has led to an increased reliance on dietary sources of vitamin D. In the United States and Canada, these sources largely consist of fortified cereals and dairy products, in addition to fish oils and egg yolks. Vitamin D from plant sources is in the form of vitamin D2, whereas that from animal sources is vitamin D3. These two forms have equivalent biologic activity and are activated equally well by the vitamin D hydroxylases in humans.

Activation of Vitamin D

Vitamin D itself is biologically inactive, and it must be metabolized to its biologically active forms. After it is consumed in the diet or synthesized in the epidermis of skin, vitamin D enters the circulation and is transported to the liver. In the liver, vitamin D is hydroxylated to form 25-hydroxyvitamin D (calcidiol; 25-hydroxyvitamin D, the major circulating form of vitamin D. The serum 25-hydroxyvitamin D concentration a useful indicator of vitamin D nutritional status. In the kidney, the 25-hydroxyvitamin D31-hydroxylase enzyme catalyzes a second hydroxylation of 25-hydroxyvitamin D, resulting in the formation of 1,25-dihydroxyvitamin D (calcitriol, 1alpha,25-dihydroxyvitamin D]—the most potent form of vitamin D. Most of the physiological effects of vitamin D in the body are related to the activity of 1,25-dihydroxyvitamin D (Figure-1)

Figure-1- showing the steps of activation of vitamin D in the body.

Sunlight exposure can provide most people with their entire vitamin D requirement. Serum vitamin D concentrations following exposure to 1 minimal erythemal dose of simulated sunlight (the amount required to cause a slight pinkness of the skin) is equivalent to ingesting approximately 20,000 IU of vitamin D2

Although excess dietary vitamin D is toxic, excessive exposure to sunlight does not lead to vitamin D toxicity, because there is a limited capacity to form the precursor, 7 dehydrocholesterol, and prolonged exposure of previtamin D to sunlight leads to formation of inactive compounds. Vitamin D toxicity (hypervitaminosis D) induces abnormally high serum calcium levels (hypercalcemia), which could result in bone loss, kidney stones, and calcification of organs like the heart and kidneys if untreated over a long period of time.

Q.2- Why is vitamin D considered a hormone? Describe the mechanism of action of vitamin D.

Answer- Vitamin D is actually a hormone since –

1) Structurally it has a cyclopentano perhydrophenanthrene nucleus, like a steroid hormone.

2) Its mechanism of action resembles that of hormones (Figure-2).

Figure-2- Showing the mechanism of action of a steroid hormone. Vitamin D has a similar action. Click the link below to see the animations of mechanism of action of a steroid hormone.

http://tube.medchrome.com/2011/10/mechanism-of-action-of-steroid-hormones.html

3) Like hormones it is required only in small amount.

4) Like hormones, the formation of the active form is subjected to feed back inhibition.

5) Like hormones, vitamin D has specific target organs like intestine, bone and kidneys.

6) Like hormones, it is produced in one organ and  acts upon distant organs for its  functions.

Mechanisms of Action

Most if not all actions of vitamin D are mediated through a nuclear transcription factor known as the vitamin D receptor (VDR). Upon entering the nucleus of a cell, 1,25-dihydroxyvitamin D associates with the VDR and promotes its association with the retinoic acid X receptor (RXR). In the presence of 1,25-dihydroxyvitamin D the VDR/RXR complex binds small sequences of DNA known as vitamin D response elements (VDREs) and initiates a cascade of molecular interactions that modulate the transcription of specific genes (Figure-3). More than 50 genes in tissues throughout the body are known to be regulated by 1,25-dihydroxyvitamin D.

 

 

 

 

 

 

 

 

Figure-3- showing the mechanism of action of vitamin D

Q.3- Justify the statement that “Vitamin D metabolism is both regulated by and regulates calcium homeostasis”. What are the other functions performed by vitamin D?

Answer- The main function of vitamin D is to maintain calcium homeostasis, and in turn, vitamin D metabolism is regulated by factors that respond to plasma concentrations of calcium and phosphate.

Maintenance of serum calcium levels within a narrow range is vital for normal functioning of the nervous system, as well as for bone growth and maintenance of bone density.

Flow chart- showing role of vitamin D in the absorption of calcium from gut.

The parathyroid glands sense the serum calcium level, and secrete parathyroid hormone (PTH) if it becomes too low, for example, when dietary calcium intake is inadequate. PTH stimulates the activity of the 1-hydroxylase enzyme in the kidney, resulting in increased production of calcitriol, the biologically active form of vitamin D3. Increased calcitriol production restores normal serum calcium levels in three different ways:

1) by activating the vitamin D-dependent transport system in the small intestine, increasing the absorption of dietary calcium(Flow chart),

2) by increasing the mobilization of calcium from bone into the circulation; and

3) by increasing the reabsorption of calcium by the kidneys (Figure-4).

PTH is also required to increase calcium mobilization from bone and calcium reabsorption by the kidneys.

When there is adequate calcium concentration, Calcitriol acts to reduce its own synthesis by inducing the 24-hydroxylase and repressing the 1-hydroxylase in the kidney. 

Other functions of vitamin D

In addition, calcitriol is involved in insulin secretion, synthesis and secretion of parathyroid and thyroid hormones, inhibition of production of interleukin by activated T-lymphocytes and of immunoglobulin by activated B-lymphocytes, differentiation of monocyte precursor cells, and modulation of cell proliferation. In most of these actions, it acts like a steroid hormone, binding to nuclear receptors and enhancing gene expression, although it also has rapid effects on calcium transporters in the intestinal mucosa.

 

 Figure-4- showing the role of vitamin D in maintaining calcium homeostasis.

Q.4 – Discuss the causes, clinical manifestations, laboratory diagnosis and treatment of vitamin D deficiency in children.

Rickets

Rickets is a disease of growing bone that is unique to children and adolescents. It is caused by a failure of osteoid to calcify in a growing person. Failure of osteoid to calcify in adults is called osteomalacia. Vitamin D deficiency rickets occurs when the metabolites of vitamin D are deficient. Less commonly, a dietary deficiency of calcium or phosphorus may also produce rickets.

Pathophysiology

In the vitamin D deficiency state, hypocalcemia develops, that stimulates excess parathyroid hormone, which acts to stimulate renal phosphorus loss, further reducing deposition of calcium in the bone. Excess parathyroid hormone also produces changes in the bone similar to those occurring in hyperparathyroidism. Early in the course of rickets, the calcium concentration in the serum decreases. After the parathyroid response, the calcium concentration usually returns to the reference range, though phosphorus levels remain low. Alkaline phosphatase, which is produced by overactive osteoblast cells, leaks to the extracellular fluids so that its concentration rises to anywhere from moderate elevation to very high levels.

Frequency

Vitamin D deficiency rickets does not occur in formula-fed infants because formula and milk sold in the United States contains 400 IU of vitamin D per liter. Except in pediatric patients with chronic malabsorption syndromes or end-stage renal disease, nearly all cases of rickets occur in breastfed infants who have dark skin and receive no vitamin D supplementation.

Causes of vitamin D deficiency

The clinical syndrome of vitamin D deficiency can be a result of-

a) deficient production of vitamin D in the skin,

b) lack of dietary intake,

c) accelerated losses of vitamin D,

d) impaired vitamin D activation or

e)  resistance to the biologic effects of 1,25(OH)2D.

The elderly people are particularly at risk for vitamin D deficiency, since both the efficiency of vitamin D synthesis in the skin and the absorption of vitamin D from the intestine decline with age.

Similarly, intestinal malabsorption of dietary fats leads to vitamin D deficiency. This is further exacerbated in the presence of terminal ileal disease, which results in impaired enterohepatic circulation of vitamin D metabolites. In addition to intestinal diseases, accelerated inactivation of vitamin D metabolites can be seen with drugs that induce hepatic cytochrome P450 mixed function oxidases, such as barbiturates, phenytoin, and rifampin.

Impaired 25-hydroxylation, associated with severe liver disease or isoniazid, is an infrequent cause of vitamin D deficiency. Impaired 1-hydroxylation is prevalent in the population with profound renal dysfunction and a decrease in functional renal mass. Thus, therapeutic interventions should be considered in patients whose creatinine clearance is <0.5 mL/s (30 mL/min).

Mutations in the renal -1-hydroxylase are the basis for the genetic disorder, pseudo-vitamin D–deficiency rickets. This autosomal recessive disorder presents with the syndrome of vitamin D deficiency in the first year of life. Patients present with growth retardation, rickets, and hypocalcemic seizures. Serum 1,25(OH)2D levels are low, despite normal 25(OH)D levels and elevated PTH levels. Treatment with vitamin D metabolites that do not require 1-hydroxylation results in disease remission, although lifelong therapy is required.

A second autosomal recessive disorder, hereditary vitamin D–resistant rickets, a consequence of vitamin D receptor mutations, is a greater therapeutic challenge. These patients present in a similar fashion during the first year of life, but alopecia often accompanies the disorder, demonstrating a functional role of the VDR ( Vitamin D receptor) in postnatal hair regeneration. Serum levels of 1,25(OH)2D are dramatically elevated in these individuals, both because of increased production due to stimulation of 1-hydroxylase activity as a consequence of secondary hyperparathyroidism and because of impaired inactivation, since induction of the 24-hydroxylase by 1,25(OH)2D requires an intact VDR. Since the receptor mutation results in hormone resistance, daily calcium and phosphorus infusions may be required to bypass the defect in intestinal mineral ion absorption.

Occasionally, deficiency severe enough to cause maternal Osteomalacia results in rickets with metaphyseal lesions in neonates.

Summary of Causes of Impaired Vitamin D action

  • Vitamin D deficiency
    • Impaired cutaneous production
    • Dietary absence
    • Malabsorption
  • Accelerated loss of vitamin D
    • Impaired enterohepatic circulation
  • Impaired 25-hydroxylation  
  • Impaired 1-hydroxylation
    • Hypoparathyroidism  
    • Renal failure
    • 1-hydroxylase mutation
  • X-linked hypophosphatemic rickets
  • Target organ resistance
    • Vitamin D receptor mutation
  • Phenytoin therapy
  • Liver disease
    •  Isoniazid therapy

    Clinical Manifestations

    • Generalized muscular hypotonia of an unknown mechanism is observed in most patients with clinical signs of rickets.
    • Craniotabes (softening of the entire skull) manifests early in infants with vitamin D deficiency, although this feature may be normal in infants, especially for those born prematurely.
    • If rickets occurs at a later age, thickening of the skull develops. This produces frontal bossing and delays the closure of the anterior fontanelle. In the long bones, laying down of uncalcified osteoid at the metaphases leads to spreading of those areas, producing knobby deformity, which is visualized on radiography as cupping and flaring of the metaphyses.
    • Weight bearing produces deformities such as bowlegs and knock-knees(Figure-5)

    Figure-5 -showing bending of bones( bow legs).

    In the chest, knobby deformities results in the rachitic rosary along the costochondral junctions (Figure-6)

    Figure-6- showing rachitic rosary along the costochondral junctions.

    The weakened ribs pulled by muscles also produce flaring over the diaphragm, which is known as Harrison groove.

     Figure-7-showing Harrison groove and pot belly

    The sternum may be pulled into a pigeon-breast deformity (Figure-7).

    Figure-8- showing chest deformity in Rickets

    In more severe instances in children older than 2 years, vertebral softening leads to Kyphoscoliosis (Figure-8)

     Figure-9-Showing Kyphoscoliosis

    The ends of the long bones demonstrate that same knobby thickening.

    At the ankle, palpation of the tibial malleolus gives the impression of a double epiphysis (Marfan sign).

    Because the softened long bones may bend, they may fracture one side of the cortex (ie, greenstick fracture).

    Figure-10-Showing the clinical findings in Rickets

    Regardless of the cause, the clinical manifestations of vitamin D deficiency are largely a consequence of impaired intestinal calcium absorption. Mild to moderate vitamin D deficiency is asymptomatic, whereas long-standing vitamin D deficiency results in hypocalcemia accompanied by secondary hyperparathyroidism, impaired mineralization of the skeleton (osteopenia on x-ray or decreased bone mineral density), and proximal myopathy. In the absence of an intercurrent illness, the hypocalcemia associated with long-standing vitamin D deficiency rarely presents with acute symptoms of hypocalcemia, such as numbness, tingling, or seizures. However, the concurrent development of hypomagnesemia, which impairs parathyroid function, or the administration of potent bisphosphonates, which impair bone resorption, can lead to acute symptomatic hypocalcemia in vitamin D–deficient individuals.

    Laboratory Investigations

    • Early on in the course of rickets, the calcium (ionized fraction) is low; however it is often within the reference range at the time of diagnosis as parathyroid hormone levels increase.
    • Calcitriol levels maybe normal or elevated because of increased parathyroid activity. Because levels of serum 25(OH)D reflect body stores of vitamin D and correlate with symptoms and signs of vitamin D deficiency better than levels of other vitamin D metabolites, 25(OH)D (D2+D3) measurement is generally considered the best way to diagnose deficiency. Goal 25(OH)D levels are 30 to 40 ng/mL (about 75 to 100 nmol/L); whether levels above this may be beneficial remains uncertain.
    • If the diagnosis is unclear, serum levels of 1,25(OH)2D and urinary Ca concentration can be measured. In severe deficiency, serum 1,25(OH)2D is abnormally low, usually undetectable. Urinary Ca is low in all forms of the deficiency except those associated with acidosis.
    • The phosphorus level is invariably low for age unless recent partial treatment or recent exposure to sunlight has occurred.
    • Alkaline phosphatase levels are elevated.
    • A generalized aminoaciduria occurs from the parathyroid activity; aminoaciduria does not occur in familial hypophosphatemia rickets (FHR).
    • PTH levels are also measured to confirm the diagnosis, because in vitamin D deficiency PTH level is high.

    Imaging Studies

    Bone changes, seen on x‑rays, precede clinical signs. In rickets, changes are most evident at the lower ends of the radius and ulna. The diaphyseal ends lose their sharp, clear outline; they are cup-shaped and show a spotty or fringy rarefaction. Later, because the ends of the radius and ulna have become noncalcified and radiolucent, the distance between them and the metacarpal bones appears increased. The bone matrix elsewhere also becomes more radiolucent. Characteristic deformities result from the bones bending at the cartilage-shaft junction because the shaft is weak. As healing begins, a thin white line of calcification appears at the epiphysis, becoming denser and thicker as calcification proceeds. Later, the bone matrix becomes calcified and opacified at the subperiosteal level.

    Treatment

    • Correction of Ca and P deficiencies
    • Supplemental vitamin D

    Ca deficiency (which is common) and P deficiency should be corrected. As long as Ca and P intake is adequate, adults with Osteomalacia and children with uncomplicated rickets can be cured by giving vitamin D 40 μg (1600 IU) po once/day. Serum 25(OH)D and 1,25(OH)2D begin to increase within 1 or 2 days. Serum Ca and phosphate increase and serum alkaline phosphatase decreases within about 10 days. During the 3rd wk, enough Ca and P are deposited in bones to be visible on x‑rays. After about 1 mo, the dose can usually be reduced gradually to the usual maintenance level of 10 to 15 μg (400 to 600 IU) once/day. If tetany is present, vitamin D should be supplemented with IV Ca salts for up to 1 wk. 

    Vitamin D Toxicity Usually, vitamin D toxicity results from taking excessive amounts. Marked hypercalcemia commonly causes symptoms. Diagnosis is typically based on elevated blood levels of 25(OH)D. Treatment consists of stopping vitamin D, restricting dietary Ca, restoring intravascular volume deficits, and, if toxicity is severe, giving corticosteroids or for children with increased skin pigmentation.

     

    Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

    Q.1- Out of Retinol or Retinoic acid – Which form is required for the gene expression and tissue differentiation and what is the mechanism of regulation of gene expression?

    Answer- Retinoic acid (RA) and its isomers act as hormones to affect gene expression and thereby influence numerous physiological processes.

    All- trans retinoic acid and 9-cis retinoic acid have active role in growth, development and tissue differentiation. They have different actions in different tissues.

    Mechanism of regulation of gene expression

    Like vitamin D, retinoic acid interacts with nuclear receptors that bind to control elements which are specific regions on the DNA to regulate the expression of specific genes.

    There are two families of nuclear retinoid receptors (RAR) that bind to All- trans retinoic acid or 9-cis retinoic acid and RXR that bind to 9-cis retinoic acid and to some of the other physiologically active retinoids. RXR can form active dimer with RAR and the receptors for calcitriol, thyroid hormone and the receptors for long chain fatty acid derivatives. The result is that a large number of genes are sensitive to control by retinoic acid.

    All-trans-RA and 9-cis-RA are transported to the nucleus of the cell bound to cytoplasmic retinoic acid-binding proteins. Within the nucleus, all-trans-RA binds to retinoic acid receptors (RAR) and 9-cis-RA binds to retinoid receptors (RXR). RAR and RXR form RAR/RXR heterodimer, which bind to regulatory regions of the chromosome called retinoic acid response elements (RARE). Binding of all-trans-RA and 9-cis-RA to RAR and RXR respectively allows the complex to regulate the rate of gene transcription. Nuclear Receptors in the Gonads increase gene expression and maintain reproductive tissues while nuclear receptors in epithelial cells regulate cell differentiation. Through the stimulation and inhibition of transcription of specific genes, retinoic acid plays a major role in cellular differentiation, the specialization of cells for highly specific physiological roles. Many of the physiological effects attributed to vitamin A appear to result from its role in cellular differentiation(Figure-1)

     

     

     

     

     

     

     

     

     

     

    Figure-1- showing the role of retinoic acid in gene expression.

    Q.2- What is visual cycle? What is the role of vitamin A in visual cycle?

    Answer- In the retina, retinaldehyde functions as the prosthetic group of the light-sensitive opsin proteins, forming rhodopsin (in rods) and iodopsin (in cones). Any one cone cell contains only one type of opsin, and is sensitive to only one color. In the pigment epithelium of the retina, all-trans-retinol is isomerized to 11-cis-retinol and oxidized to 11-cis-retinaldehyde. This reacts with a lysine residue in opsin, forming the holoprotein rhodopsin.

    As shown in Figure-2, the absorption of light by rhodopsin causes isomerization of the retinaldehyde from 11-cis to all-trans, and a conformational change in opsin. This results in the release of retinaldehyde from the protein, and the initiation of a nerve impulse. The formation of the initial excited form of rhodopsin, bathorhodopsin, occurs within picoseconds of illumination. There is then a series of conformational changes leading to the formation of metarhodopsin II, which initiates a guanine nucleotide amplification cascade and then a nerve impulse. The nerve impulse generated by the optic nerve is conveyed to the brain where it can be interpreted as vision.  The final step is hydrolysis to release all-trans-retinaldehyde and opsin. The key to initiation of the visual cycle is the availability of 11-cis-retinaldehyde, and hence vitamin A. By a series of reactions all trans retinol is converted to 11-cis- retinal which reassociates with opsin to form Rhodopsin. In deficiency, both the time taken to adapt to darkness and the ability to see in poor light are impaired.

     

     

     

     

     

     

     

     

     

     

     

    Figure-2- showing the role of vitamin A in visual cycle

    Vitamin A deficiency and vision

    Vitamin A deficiency (VAD) among children in developing nations is the leading preventable cause of blindness. The earliest evidence of vitamin A deficiency is impaired adaptation to darkness (nyctalopia), which can lead to night blindness.

    • Bitot spots – Areas of abnormal squamous cell proliferation and keratinization of the conjunctiva can be seen in young children with VAD.
    • Xerophthalmia results from keratinization of the conjunctiva.
    • Keratomalacia- In advanced deficiency; the cornea becomes hazy and can develop erosions, which can lead to its destruction (Keratomalacia).
    • Blindness due to retinal injury – Vitamin A has a major role in photo transduction.. VAD leads to a lack of visual pigments; this reduces the absorption of various wavelengths of light, resulting in blindness. 

     Q.3- Why is vitamin A commonly called Anti-infective vitamin?

    Or

    Why do the children deficient in vitamin A get more prone to respiratory and gastrointestinal infections?

    Answer- Vitamin A is commonly known as the anti-infective vitamin, because it is required for normal functioning of the immune system, and even mild deficiency leads to increased susceptibility to infectious diseases.

    1) Vitamin A and retinoic acid (RA) play a central role in the development and differentiation of white blood cells, such as lymphocytes, which play critical role in the immune response. Activation of T-lymphocytes, the major regulatory cells of the immune system, appears to require all-trans-RA binding of RAR.

    2) The skin and mucosal cells (cells that line the airways, digestive tract, and urinary tract) function as a barrier and form the body’s first line of defense against infections. Retinol and its metabolites are required to maintain the integrity and functioning of these cells. Keratinizations of mucous membranes in vitamin A deficiency add up to the risk to infections.

    3) The onset of infection reduces blood retinol levels very rapidly. This phenomenon is generally believed to be related to decreased synthesis of retinol binding protein (RBP) by the liver, since it is a negative ‘Acute phase protein’, that results in decreased circulatory concentration of the vitamin with further deterioration of the immune system. In this manner, infection stimulates a vicious cycle.

    4) Vitamin A also plays a role in iron utilization, humoral immunity, T cell–mediated immunity, natural killer cell activity, and phagocytosis.

    All the components of immune system are affected in deficiency. Hence in brief it can be said that the pathogenic invasion is enhanced and immune system is weakened in vitamin A deficiency leading to increased susceptibility to infections.

    Q.4- How does Zinc deficiency affect the functioning of vitamin A?

    Answer- Zinc deficiency is thought to interfere with vitamin A metabolism in several ways: (1) zinc deficiency results in decreased synthesis of retinol binding protein (RBP), which transports retinol through the circulation to tissues (e.g., the retina) and also protects the organism against potential toxicity of retinol; (2) zinc deficiency results in decreased activity of the enzyme that releases retinol from its storage form, retinyl palmitate, in the liver; and (3) zinc is required for the enzyme that converts retinol into retinal.  Thus zinc deficiency precipitates vitamin A deficiency producing a variety of symptoms.

     

    Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

    Vitamin C, also known as ascorbic acid, is a water-soluble vitamin. Unlike most mammals and other animals, humans do not have the ability to  synthesize vitamin C. Therefore, it has to be obtained through diet. The enzyme, L-gulonolactone oxidase, which usually would catalyze the conversion of L-gulono lactone to L-ascorbic acid, is defective due to a mutation or inborn error in carbohydrate metabolism.

    Functions of Vitamin C

    A)

    1) Antioxidant role- Vitamin C is the major water-soluble antioxidant within the body. The vitamin readily donates electrons to break the chain reaction of lipid peroxidation. The water-soluble properties of vitamin C allow for the quenching of free radicals before they reach the cellular membrane. Tocopherol (Vitamin E) and glutathione also rely on Ascorbic acid (AA) for regeneration back to their active isoforms (Figure). The relationship between AA and glutathione is unique. Vitamin C reduces glutathione back to the active form. Once reduced, glutathione will regenerate vitamin C from its dehydro Ascorbic acid or oxidized state.

     

    Figure-showing the interrelationship of vitamin C, E and Glutathione.

    Vitamin C is required as a redox agent, reducing metal ions in many enzymes and removing free radicals. In this capacity, it protects DNA, protein, and vessel walls from damage caused by free radicals.

    2) Amino acid Metabolism- Ascorbic acid has been implicated in –

    a) Tryptophan metabolism- for hydroxylation of tryptophan to serotonin

    b) Tyrosine metabolism- For oxidation of para hydroxy phenyl pyruvate to homogentisic acid.

    B)

    1) Bone  formation-Vitamin C is required for the activity  of osteoblasts to form osteoid. the intercellular cementing substance. In vitamin C deficiency without the normal ground substance, the deposition of  bone is arrested.The resulting scorbutic bone is weak and fractures easily.

    2) Bile acid  synthesis- 7-alpha hydroxylase- the enzyme needed for the first step in bile acid synthesis, cholesterol 7-alpha hydroxylase, is dependent upon the presence of vitamin C. Bile acid formation, and hence cholesterol degradation are highly dependent on AA. Some hypothesize that vitamin C may even have a hypocholesterolemic effect.

    3) Brain function- Ascorbic acid regulates the activity of some neurons within the brain– Some of these functions include neurotransmitter membrane receptor synthesis, and neurotransmitter dynamics. Indirectly, AA plays important regulatory roles throughout the entire body due to its involvement in the synthesis of hormones, hormone-releasing factors, and neurotransmitters.

    C)

    1) Collagen formation- Vitamin C is necessary for the triple-helix formation of collagen. Vitamin C dependent Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen. Deficiency of vitamin C leads to impaired collagen synthesis, causing capillary fragility, poor wound healing, and bony abnormalities in affected adults and children.

    2) Carnitine synthesis- Trimethyllysine and γ -butyrobetaine hydroxylases are required for the synthesis of carnitine. Carnitine synthesis prefers to use vitamin C as the reducing agent. Carnitine facilitates the beta-oxidation of fat, through its role of transporting long chain fatty acids from the cytoplasm into the mitochondrial matrix of cardiac and skeletal muscle.

    3) Complement synthesis- Vitamin C dependent  Proline hydroxylase is also required in formation of C1q component of complement.

    4) Clotting-  vitamin C has an important role in the coagulation of blood. Vitamin C requiring Aspartate -Β hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K–dependent protease that hydrolyzes activated factor V in the blood-clotting cascade.

    5) Catecholamine synthesis- Dopamine Β-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines, norepinephrine, and epinephrine, from tyrosine in the adrenal medulla and central nervous system. During hydroxylation the Cu+ is oxidized to Cu2+; reduction back to Cu+ specifically requires ascorbate, which is oxidized to monodehydroascorbate. Vitamin C is directly involved in the enzyme activity of these copper dependent mono-oxygenases, which are important in the formation of catecholamines and serotonin.

    D)

    Drug detoxification- It is a component of many drug-metabolizing enzyme systems, particularly the mixed-function oxidase systems.

    E)

    Enzymes– Vitamin C is the coenzyme for two groups of hydroxylases. These are copper-containing hydroxylases and the α-ketoglutarate-linked iron-containing hydroxylases. In addition, it has a number of nonenzymic effects as a result of its action as a reducing agent and oxygen radical quencher.

    F)

    Folic acid metabolism- Ascorbic acid is required  for reducing folic acid to its tetrahydrofolate form. Thus it helps in the maturation of red blood cells.

    G)

    General body growth- Vitamin C has a  protective role and  because of its role in disease prevention, it stimulates general body growth.

    H)

    1) Haemoglobin– Vitamin C is helpful in the reconversion of met haemoglobin to haemoglobin.

    2) Hormone synthesis vitamin C is also a cofactor in the synthesis of  peptide hormones, corticosteroids, and aldosterone.

    I)

    1)  Iron metabolism– The vitamin is an important aid in the absorption and conversion of iron to its storage form. This may contribute to the anemia seen with vitamin C deficiency.

    2) Immunity- Vitamin C has been proposed to have pharmacological benefits in preventing cancer, infections, and the common cold. The role of vitamin C in preventing cancer is controversial, but has been studied for cancers of the oral cavity, uterus, esophagus, bladder, and pancreas.

    Vitamin C affects several components of the human immune system; for example, vitamin C has been shown to stimulate both the production and function of leukocytes ,especially neutrophils, lymphocytes, and phagocytes. Specific measures of functions stimulated by vitamin C include cellular motility chemotaxis, and phagocytosis. Neutrophils, which attack foreign bacteria and viruses, seem to be the primary cell type stimulated by vitamin C, but lymphocytes and other phagocytes are also affected .

     

    Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

    Spot- 1                     

    A 4- year-old child has been brought to  OPD with a complaint of difficulty in walking. Physical examination reveals bowed legs, as shown in the picture . Make a probable diagnosis for this patient. What is the biochemical basis for this manifestation? What other manifestations could be present in this child? How will you confirm the diagnosis?

     

    Answer- The child has bowed legs and appears to be suffering from Rickets. Rickets is caused by a failure of osteoid to calcify in growing children. It occurs due to vitamin D deficiency. Failure of osteoid to calcify in adults is called osteomalacia.

    The other manifestations in rickets could be – frontal bossing, knock-knees, rachitic rosary along the costochondral junctions, Harrison groove and in more severe instances in children older than 2 years, vertebral softening leading to Kyphoscoliosis. In the long bones, laying down of uncalcified osteoid at the metaphysis leads to spreading of those areas, producing knobby deformity, which is visualized on radiography as cupping and flaring of the metaphysis.

    The diagnosis is confirmed by estimating serum calcium, phosphorus, alkaline phosphatase and vitamin D levels. All are low except alkaline phosphatase which is high. Urinary calcium is decreased while phosphorus is increased.

    Spot-2

    A 32- year- old obese male has reported to the emergency with epistaxis. History reveals that he was on “Orlistat”for weight reduction since one year. What is the relationship between Orlistat and epistaxis?

     

    Answer- The patient has most probably developed vitamin K deficiency. Absorption of vitamin K might have been decreased by Orlistat (weight loss medication). Vitamin K deficiency is uncommon in healthy adults but occurs in individuals with gastrointestinal disorders, fat malabsorption or liver disease, or after prolonged antibiotic therapy coupled with compromised dietary intake. Impaired blood clotting is the clinical symptom of vitamin K deficiency, which is demonstrated by measuring clotting time. In severe cases, bleeding occurs.

    Spot-3

    A child from a very poor socio economic background has reported with loss of vision. Ophthalmological examination reveals dry conjunctiva as shown in the picture. Make a probable diagnosis. What is the underlying cause for blindness?

     

    Answer- The child is suffering from xerophthalmia (dryness of the conjunctiva)  due to vitamin A deficiency. The earliest symptom of vitamin A deficiency is impaired dark adaptation, or night blindness. Severe deficiency causes xerophthalmia, ultimately resulting  in corneal ulcers, scarring and blindness.

    Spot-4

    A 4 -year-old boy has been brought for consultation for bleeding gums and hematuria. He is the 12th born in a poor family, where one previous child died from malnutrition and dehydration in the period of infancy.  The child is fed only with cow’s milk and biscuits. What could be the basis for these clinical manifestations?

     

    Answer- The child is suffering from Scurvy (Vitamin C deficiency). The incidence of scurvy peaks in children who are fed a diet deficient in citrus fruits or vegetables. Vitamin C is necessary for the triple-helix formation of collagen. Deficiency of vitamin C leads to impaired collagen synthesis, causing capillary fragility, poor wound healing, and bony abnormalities in affected adults and children. Bleeding from gums and from other sites after a minor trauma, are typical of vitamin C deficiency. Edema may occur late in the disease.

    Spot-5

    A term infant is born and does well with breast-feeding. Two days later, the mother calls frantically because baby is bleeding from the umbilical cord and nostrils. What is the cause of bleeding? How can this be treated?

     

    Answer- The child is suffering from vitamin K deficiency.

    Hemorrhagic disease of newborn is caused by poor transfer of maternal vitamin K through placenta and by lack of intestinal bacteria in the infant for synthesis of vitamin K. The intestine is sterile at birth and becomes colonized over the first few weeks.

    Vitamin K is required for the synthesis of blood clotting proteins. Vitamin K is the coenzyme for the carboxylation of the glutamate residues in the post translational modifications of proteins to form the unusual amino acid γ-carboxy Glutamic acid. γ-Carboxyglutamate chelates calcium ions, and so permits the binding of the blood clotting proteins to membranes.

    Because of these factors, Vitamin K is routinely administered to newborns. Deficiency of fat soluble vitamins A, E, D and K can occur with intestinal malabsorption, but avid fetal uptake during pregnancy usually prevents infantile symptoms.

    Spot-6

    A 20 –year-old female has reported with glossitis and angular stomatitis. She is a strict vegetarian and belongs to a hilly region where cereals are traditionally dried in the open air and are thus exposed to sunlight.  She frequently gets this problem. What be the cause for her problem?

    Answer- The patient has riboflavin deficiency.

    Riboflavin is found mainly in food of high nutritional value such as meat, milk, eggs and germs of cereals. Therefore, riboflavin deficiency is always associated with malnutrition or hypo-alimentation. Riboflavin is photosensitive and disintegrates when food is dried or stored in open daylight.

    Riboflavin deficiency mostly manifests itself at the edge of the mucosa. Frequently, there are painful fissures at the angles of the mouth (angular stomatitis), fissures of the lips (Cheilosis), an inflammation of the periglottis (glossitis) and a seborrheic dermatitis of the nasolabial area and the eyelids .

    Spot-7

    Which vitamin supplementation is given to a pregnant mother to protect the fetus from neural tube defects?

     

    Answer-Neural Tube Defects (NTDs) are birth defects of the brain and the spinal cord. In anencephaly, upper end of the neural tube fails to close. The brain either never completely develops or is totally absent.  In spina bifida, neural tube fails to close on lower end. Spinal cord and back do not develop properly. Encephalocele causes protrusion of brain or membranes through an occipital defect of the Neural Tube.

    It has been demonstrated that periconceptional (before and during the first 28 days after conception) supplementation of women with folic acid can decrease the risk of neural tube defects (malformations of the brain and spinal cord, causing anencephaly or spina bifida). Therefore, a daily intake of 400 µg folic acid in addition to a healthy diet 8 weeks prior to and during the first 12 weeks after conception is recommended. There is evidence that adequate folate status may also prevent the incidence of other birth defects, including cleft lip and palate, certain heart defects and limb malformations. To reduce the risk of neural tube defects, cereal grains are fortified with folate in some countries.

     Spot-8

     

    What is egg white injury ?

    Answer-

    Raw egg whites contain Avidin, a glycoprotein that strongly binds with biotin and prevents its absorption. Thus, the ingestion of large quantities of raw egg white over a long period can result in a biotin deficiency.Cooking  denatures avidin which prevents its binding with biotin, hence no deficiency upon consumption of cooked eggs.

    Spot-9

     

     

    Maize eaters generally have skin rashes resembling pellagra. What is its biochemical basis?

    Answer- Maize lacks Tryptophan, and niacin present in it is bound to certain components and is not bioavailable. Tryptophan contributes as much as two-thirds of the niacin activity required by adults in typical diets. Lack of tryptophan and niacin in maize causes niacin deficiency manifested as pellagra. Specific food processing, such as the treatment of corn with lime water, increases the bioavailability of nicotinic acid in these products and can prevent pellagra. Pellagra is characterized by a photosensitive dermatitis. As the condition progresses, there is dementia and possibly diarrhea. Untreated pellagra is fatal.

    Spot-10

    The blood picture of a strict vegetarian female patient, presenting with weakness, fissured tongue and paralysis is displayed. Make a probable diagnosis. What will be the line of treatment?

     

    Answer-  The patient is suffering from megaloblastic anemia. Although it is synthesized exclusively by microorganisms, for practical purposes vitamin B12 is found only in foods of animal origin, there being no plant sources of this vitamin. This means that strict vegetarians (Vegans) are at risk of developing B12 deficiency. Vitamin B12 Deficiency Causes Functional Folate Deficiency—the “Folate Trap”. Deficiency of folic acid itself or deficiency of vitamin B12, which leads to functional folic acid deficiency, affects cells that are dividing rapidly because they have a large requirement for thymidine for DNA synthesis. Clinically, this affects the bone marrow, leading to megaloblastic anemia. A combination of folic acid and B12 is given to treat megaloblastic anemia.

    Spot-11 

    Why is it said that babies undergoing phototherapy for physiological jaundice are prone to develop riboflavin deficiency?

     

     

    Answer- Riboflavin is stable when heated and is not easily destroyed in the ordinary processes of cooking but it is light-sensitive so it is degraded easily by light, that is why infants undergoing phototherapy for jaundice  become prone to this deficiency. Loss of riboflavin is also seen if foods are left out in sunlight or in UV light. Because of this light sensitivity, riboflavin rapidly disappears from milk kept in glass bottles exposed to the sun or bright daylight (85% within 2 hours).

    Spot-12

    A 56 – year-old male on Isoniazid Therapy for tuberculosis has developed rashes on the exposed parts of the body. What is the probable cause for these rashes?

    Answer- The patient has developed pellagra. Prolonged treatment with the anti-tuberculosis drug, Isoniazid, has resulted in niacin deficiency. Isoniazid may induce a state of pyridoxine deficiency by combining with pyridoxine and generating inactive isoniazid-pyridoxal hydrozones, thus depleting the supply of pyridoxine. Pyridoxine is needed in the endogenous pathway of niacin synthesis. Thus diminished synthesis of niacin ultimately produces pellagra, which is manifested by skin rashes as seen in the picture.

    Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

    Advertisement