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16-A young man with normocytic anemia, jaundice, and splenomegaly was diagnosed as having RBC pyruvate kinase deficiency after a peripheral blood smear showed spiculated cells. Since in this patient pyruvate kinase is abnormal not only is less pyruvate made but intermediates above pyruvate in the glycolytic pathway build up slowing the pathway. Which of the following products may not be made in the appropriate amounts in the RBC because of the deficiency of pyruvate?

a) Glucose

b) Oxaloacetate

c) Acetyl CoA

d) Lactate

e) Citrate

17-A morbidly obese woman decides to see her physician to begin a weight loss program. He tells her that diet and exercise play an essential role in her program. She is concerned that she does not have time to devote to exercise and wants to know if there is any pharmacological treatment for her. The physician decides to start her on Orlistat which directly inhibits absorption of fats. Which of the following steps is directly inhibited by Orlistat ?

a) Bile salt formation

b) Micelle formation

c) Pancreatic and gastric lipase

d) Absorption of Free fatty acids

e) Chylomicron formation

18- A known alcoholic was found  lying semiconscious by his landlady at the bottom of a stairwell with a broken arm,  he was  then taken to the emergency room. Initial laboratory studies showed  relatively large anion gap of 34 (normal = 9 to 15). His blood alcohol was elevated at 245 mg/dL (intoxication level = 150 to 300 mg/dL), and his blood glucose was 38 mg/dL (low normal). The patient/s large anion gap and hypoglycemia can best be explained by which of the following?

a) Decreased secretion of glucagon

b) Increased secretion of insulin

c) Increased urination resulting from the diuretic effect of alcohol

d) Inhibition of dehydrogenase enzymes by NADH

e) Inhibition of glycogenolysis by ethanol

19- Which of the following changes in hepatic metabolism best explains the increased incidence of ketoacidosis observed in type I diabetes?

a) Increased glucose uptake

b) Increased protein synthesis

c) Increased lipoprotein synthesis

d) Increased β-oxidation

e) Increased glycogen breakdown

20- A 16-month-old girl was found to have ingested approximately 30 mL of an acetonitrile-based cosmetic nail remover when she vomited 15 minutes post ingestion. The poison control center was contacted, but no treatment was recommended because it was confused with an acetone-based nail polish remover. The child was put to bed at her normal time, which was 2 hours post ingestion. Respiratory distress developed sometime after the child was put to bed, and she was found dead the next morning.
Inhibition of which of the following enzymes was the most likely cause of this child’s death?

a) Cytochrome c reductase

b) Cytochrome oxidase

c) Coenzyme Q reductase

d) NADH dehydrogenase

e) Succinate dehydrogenase

21- A 12-year-old girl is presented at the clinic with reports of frequent fainting and lethargy. The girl is 5 ft tall and weighs 80 lb. Skin fold tests show an abnormally low percentage of body fat mass. Which of the following hormones is likely to be severely diminished in the patient described above?

a) Cortisol

b) Epinephrine

c) Glucagon

d) Insulin

e) Thyroxin

22- A patient presents with a urinary tract infection and is prescribed a combination drug containing Trimethoprim and sulfamethoxazole. These drugs are effective because they do which of the following?

a) Bind to operon to prevent synthesis of bacterial mRNA

b) Block transport across bacterial cell walls

c) Inhibit bacterial synthesis of Cobalamine (B12)

d) Inhibit bacterial synthesis of THF

e) Inhibit synthesis of phospholipids in bacteria

23- 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

24- A deficiency in thiamine (vitamin B1) would most likely lead to which of the following clinical manifestations?

a) Decrease in carboxylase enzyme activity

b) Decrease in serum lactate concentration

c) Decrease in red blood cell Transketolase activity

d) Increase in urinary methylmalonate

e) Increase in prothrombin time

25- Leukemia patients are often given the compound Leucovorin (N5-formyl THF) following treatment with the drug Methotrexate. Why is Leucovorin useful as part of this treatment protocol?

a) It facilitates the uptake of methotrexate by cells

b) It can be converted to THF by bypassing DHFR

c) It acts as an activator of Thymidylate synthase

d) It prevents the uptake of methotrexate by normal cells

e) It stimulates cells of the immune system

26-Megaloblastic anemia has two most likely causes, deficiency of folate and deficiency of cobalamin. Often treatment of patients with Cobalamine deficiency improves in terms of their hematologic features with treatment with folate but not in their neurologic symptoms. What is the most likely explanation for this explanation?

a) Cobalamine deficiencies are not serious

b) Excess folate blunts the trapping of folate as N5-methyltetrahydrofolate

c) Folate in high concentrations can serve as cofactor for the conversion of homocysteine to methionine

d) Excess folate directly inhibits the destruction of red blood cells

e) Excess folate stimulates erythropoietic tissues to synthesize cobalamin in situ

27-What would be the consequences of a deficiency of vitamin B12 on fatty acid oxidation? Which of the following  metabolic intermediates might accumulate?

a) Acetyl co A

b) Succinyl co A

c) Propionyl co A

d) Acetoacetyl co A

e) Methyl malonyl co A

28-A 30-month-old female child whose growth rate has been in the lower 10th percentile over the last year presents with chronic, nonproductive cough and diarrhea with foul-smelling stools. She is diagnosed as having cystic fibrosis. For which of the following vitamins is this child most likely to be at risk of deficiency?

a) Ascorbic acid (vitamin C)

b) Biotin

c) Folic acid

d) Retinol (vitamin A)

e) Riboflavin (vitamin B2)

29-An unskilled worker in a water garden was sent to sweep up a spill of a white powder in the storage shed. Later he was found with labored breathing and convulsions. On further examination, the white powder was identified as rotenone . Respiratory distress is induced on rotenone exposure because it inhibits the complex that catalyzes which of the following?

a) Electron transfer from NADH to coenzyme Q

b) Oxidation of coenzyme Q

c) Reduction of cytochrome c

d) Electron transfer from cytochrome c to cytochrome a1/a3

e) Electron transfer from cytochrome a1/a3 to oxygen

30- Which of the following tissues can metabolize glucose, fatty acids, and ketone bodies for ATP production?

a) Liver

b) Muscle

c) Brain

d) Red blood cells

e) White blood cells


16- d)- RBCs do not have  mitochondria hence glucose cannot be synthesized from pyruvate  and pyruvate can not be converted to acetyl-CoA or Oxaloacetate, because the corresponding enzymes, Pyruvate dehydrogenase complex and pyruvate carboxylase  are mitochondrial, hence these conversions are not possible.  But  RBCs do have lactate dehydrogenase enzyme and conversion to lactate is possible. The conversion depends on pyruvate levels. In the deficiency of pyruvate kinase , pyruvate concentration is low thus lactate formation is also reduced.

17- Orlistat inhibits gastric and pancreatic lipases, preventing the digestion and absorption of fats. The normal sequence of digestion is that triglycerides are emulsified by bile salts. These are then acted on by lipases. The product of digestion are absorbed and reesterified in the intestinal mucosal cells to form triglycerides which are packed in the Chylomicrons for transportation out to the peripheral cells for utilization. Under the effect of orlistat triglycerides are left undigested and unabsorbed, resulting in bulky stools. Over a period of time, orlistat therapy can induce deficiency of fat soluble vitamins.

18- d)- Alcoholics frequently do not eat while binge drinking, so it is most likely that his liver glycogen stores became depleted and he could not increase his blood glucose levels due to impaired gluconeogenesis. Key gluconeogenic dehydrogenases are inhibited by the elevated levels of NADH, including lactate dehydrogenase, glycerol 3-phosphate dehydrogenase, and malate dehydrogenase. The precursors for gluconeogenesis are not available due to shifting of equilibrium of the reactions towards formation of Lactate, glycerol-3-P and malate. Thus dietary unavailability coupled with reduced gluconeogenesis is the cause for hypoglycemia.

The large anion gap is due to lactic acidosis and keto acidosis.

Lactic acidosis is due to accumulation of lactate.The metabolic stress leads to the increase in secretion of epinephrine and other hormones that mobilize fatty acids from stored triglycerides in adipose cells. These fatty acids undergo β-oxidation in the liver and are converted to ketone bodies because of the inhibition of the TCA cycle by high levels of NADH produced by the oxidation of ethanol first to acetaldehyde and acetate. Thus excess Acetyl co A is converted to ketone bodies causing ketoacidosis.

19- d)- Decreased circulating insulin signals a need to increase hepatic glucose production. This is an energetically demanding process, driven by β-oxidation of fatty acids. However, acetyl-CoA, the major end product of β-oxidation, cannot be used for glucose production. Instead, acetyl-CoA is shunted into the pathway of ketone body synthesis (ketogenesis). In contrast, carbon from intrahepatic glycogen will contribute less to ketone body synthesis in uncontrolled type I diabetes mellitus. Net glucose uptake, protein synthesis, and lipoprotein synthesis are decreased in uncontrolled type I diabetes.

20- b. The culprit here is cyanide produced from acetonitrile. Cyanide inhibits the cytochrome oxidase of electron transport chain .

21- d. The low body weight and fat mass observed in the patient are consistent with a metabolically “fasted” state. During such a condition, circulating insulin levels will be low, whereas counter regulatory hormones (e.g., glucagon, epinephrine, and cortisol) will be elevated.

22- d) Bacteria must synthesize folate that is required for their biosynthetic processes; they do not have a transporter to bring folate into the cell. Trimethoprim inhibits prokaryotic DHFR (eukaryotic is not affected) and sulfamethoxazole is an analog of p-amino benzoic acid (PABA), a precursor to folic acid. Bacteria will use this analog instead of PABA and produce a nonfunctional folate. Both are examples of competitive inhibition.

23- e)-The patient has demonstrated a deficiency in riboflavin (urinary excretion of less than 30 μg/mg creatinine is considered clinically deficient). Riboflavin is a component of the cofactor FAD (flavin adenine dinucleotide), which is required for the conversion of succinate to fumarate by succinate dehydrogenase.

24- c) In addition to being an important cofactor for the enzymes involved in the oxidative decarboxylation of pyruvate, α-ketoglutarate, and branched-chain α-ketoacids, thiamine is also a cofactor for the enzyme Transketolase, the enzyme that transfers aglycoaldehyde group from a ketose sugar to an aldose sugar in the pentose phosphate pathway.
One of the diagnostic tools in determining a thiamine deficiency is determination of the activity of red blood cell Transketolase in the presence and absence of added thiamine. A thiamine deficiency would be expected to increase blood lactate concentrations. A deficiency of biotin would lead to decreased carboxylase activity, whereas an increased methylmalonate concentration would be
observed with a deficiency in vitamin B12. A deficiency in vitamin K would lead to an increase in prothrombin time.

25- b) Leucovorin (N5-formyl THF, folinic acid) is used as an antidote for cells that have decreased levels of folic acid. Treatment of leukemia patients with methotrexate kills the tumor cells but also other normal rapidly dividing cells. N5-formyl THF is normally administered 24 hours following treatment with methotrexate; it can be converted to THF by these normal cells by bypassing the block caused by methotrexate. Therefore, these normal cells can synthesize deoxythymidine and carry out DNA synthesis. Methotrexate inhibits dihydrofolate reductase enzyme.

26- b) Excess folate, by overwhelming the folate pool trapped as N5- methyl tetrahydrofolate, can allow for formation of N5,N10-methylene tetrahydrofolate which is required for the thymidylate synthase reaction for DNA synthesis and red blood cell formation. Folate is not recognized as a methyl donor by methionine synthase. Folate does not inhibit destruction of erythrocytes. Cobalamine is an important critical vitamin not synthesized by humans.

27 – e)-Vitamin B12 is a coenzyme prosthetic group for methylmalonyl-CoA mutase. This enzyme is active in metabolism of odd-chain fatty acids. The last round of β oxidation releases acetyl-CoA and propionyl-CoA from odd-chain fatty acids. Propionyl-CoA is further metabolized by being converted to (D)-methylmalonyl-CoA by propionyl-CoA carboxylase, a biotin-containing enzyme. (D)-Methylmalonyl-CoA racemase then converts (D)-methylmalonyl-CoA to (L)-methylmalonyl-CoA, which is metabolized to succinyl CoA by methylmalonyl-CoA mutase. This enzyme is a vitamin B12-dependent enzyme, and a deficiency in vitamin B12 will cause a build-up of (L)-methylmalonyl-CoA. 

Depending on the amount of odd chain fatty acids (and Propionic acid) in the diet, a deficiency of B12 is expected to act as a coenzyme A trap, slowly accumulating coenzyme A as methylmalonyl-CoA. The affected patients present with Methylmalonic aciduria.

28- d)  Because cystic fibrosis leads to pancreatic damage and diminution of the ability to secrete HCO3 ions and pancreatic digestive enzymes with the result that fat and protein are absorbed poorly. Retinol is a fat soluble vitamin that must be absorbed along with lipid micelles; other fat-soluble vitamins are E, D, and K. The other vitamins listed are water-soluble and their absorption is not significantly affected. Hence in cystic fibrosis fat soluble vitamin deficiency(vitamin A in the given case) is expected.

29 – The right answer is a).

Rotenone binds avidly to the flavoprotein NADH CoQ reductase, complex I (also called NADH dehydrogenase). The central portion of the rotenone structure resembles the isoalloxazine ring of the FMN molecule, and when it binds to complex I, rotenone prevents the transfer of electrons from NADH to coenzyme Q.

 30- The right answer is (b). Muscle cells are the only cells that are capable of utilizing all the energy sources available- glucose, fatty acids and during starvation ketone bodies. Mitochondria are required for the utilization of fatty acids and ketone bodies. Since red blood cells do not contain mitochondria, no utilization of these energy sources is possible. Although brain can utilized glucose and ketone bodies but the fatty acid cannot cross through blood brain barrier. Liver cells are the sites for ketone body production, but the mitochondrial enzyme necessary for utilization of ketone bodies is not present in hepatocytes.


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