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).
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