a. Step A

b. Step B

c. Step C

d. Step D

e. Step E

47. A comatose 25-year-old Asian female is brought by ambulance to the emergency room from a campus chemistry laboratory where she works as a teaching assistant. Vital signs reveal a temperature of 40.5°C (105°F) with rapid heart and respiratory rates. Along one arm is a yellow stain and her blood pressure is unobtainable. Two students accompany her and report that she was giving a demonstration on metabolic inhibitors and had an accidental spill on her face, first joking and complaining of blurred vision, then having headaches and shaking movements before passing out. Which of the following is the most likely toxin?

a. Phenobarbital

b. Carboxin

c. Dimercaprol

d. Dinitrophenol

e. Cyanide

48. Dehydrogenases such as glucose-6-phosphate dehydrogenase serve to transfer H+ from one substrate to another in coupled oxidation-reduction reactions, ultimately (in the respiratory chain) generating energy by oxygen/water reduction. Dehydrogenases can use which of the following compounds as an electron acceptor?

a. H₂O

b. NAD+

c. O₂

d. Peroxide

e. NADPH

49. Nicotine addiction from cigarette smoking is related to rates of conversion of nicotine to cotinine, carried out by a member of the cytochrome P450 enzyme family called P450PB (formerly CYP2A3-MIM*122720). Individuals with variant alleles of the enzyme are predisposed toward nicotine addiction and the development of lung cancer. The P450 cytochromes are members of which family of oxidoreductases?

a. Catalase

b. Hydroperoxidase

c. Oxidase

d. Oxygenase

e. Dehydrogenase

50. Which of the following compounds is a high-energy phosphate donor to ATP during glycolysis?

a. Glucose 6-phosphate

b. Glucose 1-phosphate

c. Phosphoenolpyruvate

d. Phosphoglyceric acid

e. Fructose 6-phosphate

51. Which of the following are products of triacylglycerol breakdown and subsequent β-oxidation that may undergo gluconeogenesis?

a. Propionyl-CoA

b. Acetyl-CoA

c. All ketone bodies

d. Some amino acids

e. β-Hydroxybutyrate

52. Which of the following regulates lipolysis in adipocytes?

a. Activation of fatty acid synthesis mediated by cyclic AMP

b. Activation of triglyceride lipase as a result of hormone-stimulated increases in cyclic AMP levels

c. Glycerol phosphorylation to prevent futile esterification of fatty acids

d. Activation of cyclic AMP production by insulin

e. Hormone-sensitive lipoprotein lipase

53. Oligomycin is an antibiotic derived from Streptomyces, a genus of soil bacteria that has contributed over two-thirds of naturally derived antibiotics used in humans. Oligomycin is a macrolide antibiotic (containing a large macrolide ring-like erythromycin or azithromycin) that inhibits ATP synthase required for oxidative phosphorylation. Which of the following options best explains the consequence of this inhibition?

a. Selective disruption of complex II function

b. Disruption of ubiquinone phosphorylation

c. Disruption of NADH entry into the respiratory chain

d. Disruption of proton flow across the inner mitochondrial membrane

e. Disruption of heme oxygen action

54. Patients with fatty acid oxidation disorders are particularly susceptible to periods of fasting with disproportionate impact on muscular tissues. This is because, relative to energy from oxidation of glycogen (4 kcal/g or, when hydrated, 1.5 kcal/g), the yield from oxidation of triacylglyceride stores is which of the following?

a. 1 kcal/g

b. 2 kcal/g

c. 4 kcal/g

d. 9 kcal/g

e. 24 kcal/g

55. A 24-hour-old Caucasian female infant has a rapid respiratory rate, often due to retained fluid from delivery (transient tachypnea of the newborn). The child then has feeding problems due to low muscle tone (hypotonia), and this seems to have central (nervous system) rather than peripheral origin, implying an encephalopathy. A liver biopsy reveals a very low level of acetyl-CoA carboxylase, but normal levels of the enzymes of glycolysis, gluconeogenesis, the citric acid cycle, and the pentose phosphate pathway. Which of the following is the most likely cause of the infant’s respiratory problems?

a. Low levels of phosphatidylcholine

b. Excess adrenal fatty acids

c. Ketoacidosis

d. High levels of citrate

e. Glycogen depletion

56. Patients with riboflavin deficiency will have lower FAD levels, while those with niacin deficiency will have lower NAD levels. How do oxidations involving NAD compare with those involving FAD?

a. NAD-linked oxidations generate 3 mol ATP per half mole of O₂ consumed, whereas FAD-linked oxidations only generate 2 mol ATP per half mole of O₂ consumed.

b. FAD-linked oxidations generate 3 mol ATP per half mole of O₂ consumed, whereas NAD-linked oxidations only generate 2 mol ATP per half mole of O₂ consumed.

c. Both oxidations generate 2 mol ATP per half mole of O₂ consumed.

d. Both oxidations generate 3 mol ATP per half mole of O₂ consumed.

e. Both oxidations add hydrogens to substrates.

57. Individuals with disorders of the respiratory chain are often placed on supplements containing riboflavin and coenzyme Q. Which of the following is the role of coenzyme Q (ubiquinone) in the respiratory chain?

a. It links flavoproteins to cytochrome b, the cytochrome of lowest redox potential.

b. It links NAD-dependent dehydrogenases to cytochrome b.

c. It links each of the cytochromes in the respiratory chain to one another.

d. It is the first step in the respiratory chain.

e. It is a hydrogen receptor from NADH.

58. In the resting state, what is the primary condition that limits the rate of respiration?

a. Availability of ADP

b. Availability of oxygen

c. Availability of substrate

d. Availability of both ADP and substrate

e. Availability of oxygen and ATP

59. Oxidative phosphorylation couples generation of ATP with which of the following?

a. Proton translocation

b. Substrate level phosphorylation

c. Electron flow through cytochromes

d. Reduction of NADH

e. Reduction of water

60. In the past, the uncoupler 2,4-dinitrophenol was used as a weightreducing drug until side effects such as fatigue and breathlessness precluded its use. How could the use of this drug result in weight loss?

a. 2,4-dinitrophenol is an allosteric activator of ATP synthase and thus increases the rate of H⁺ translocation and oxidation of fats and other fuels.

b. 2,4-dinitrophenol inhibits transport of pyruvate into the mitochondria. Fats are therefore metabolized to glycerol and subsequently to pyruvate, depleting fat stores.

c. 2,4-dinitrophenol allows oxidation of fats in adipose tissue without production of ATP. Fat oxidation can thus proceed continuously and fat stores will be used up.

d. 2,4-dinitrophenol causes ATP to be produced at a higher rate than normal, thus causing weight loss.

e. 2,4-dinitrophenol causes ADP to decrease and thus to increase rates of oxidative phosphorylation.

61. Many compounds poison the respiratory chain by inhibiting various steps of oxidation or phosphorylation. Which of the following steps is inhibited by carbon monoxide and cyanide?

a. Oxidation step between cytochrome and coenzyme Q and distal cytochromes

b. Oxidation step involving direct reduction of oxygen

c. Uncoupling of oxidation from phosphorylation

d. Oxidation step between cytochromes c and b

e. Oxidation step of flavin cytochromes to coenzyme Q

62. An important difference between respiratory chain inhibitors and uncouplers is which of the following?

a. The effect of respiratory chain inhibitors cannot be characterized spectroscopically, whereas that of uncouplers can.

b. Uncouplers do not inhibit electron transport, but respiratory chain inhibitors do.

c. Uncouplers are toxic substances, but respiratory chain inhibitors are not.

d. Respiratory chain inhibitors allow leakage of protons across the membrane, but uncouplers do not.

e. Uncouplers accept protons from NADH before they can be transported across the mitochondrial membranes.

63. Why is the yield of ATP from the complete oxidation of glucose lower in muscle and brain than in kidney, liver, and heart?

a. Different shuttle mechanisms operate to transfer electrons from the cytosol to the mitochondria in the two sets of tissues.

b. Muscle and brain cells have a lower requirement for ATP.

c. There are fewer mitochondria in muscle and brain cells.

d. There are fewer ATP synthases in muscle and brain cells.

e. Mitochondrial glycerophosphate dehydrogenase uses NAD rather than FAD.

64. The problem of regenerating NAD⁺ from NADH for cytoplasmic processes by using mitochondria is solved in the most energy-efficient manner by which of the following?

a. Reversing the direction of enzyme reactions like pyruvate dehydrogenase

b. Locating certain cytochromes in the cytoplasm

c. Shuttling of coupled reaction substrates like malate to aspartate

d. Reversing the direction of glycolysis

e. Direct oxidation of NADH by cytochromes P450

65. A certain class of disease is produced because of the tissue’s lack of certain metabolic pathways. Which one of the following tissues can metabolize glucose, fatty acids, and ketone bodies for ATP production?

a. Liver

b. Muscle

c. Hepatocytes

d. Brain

e. Red blood cells

Protein Function and Bioenergetics

Answers

31. The answer is a. (Murray, pp 48-56, 660-665. Scriver, pp 4571-4636.) The female would exhibit respiratory acidosis due to shortness of breath and decreased efficiency of gas exchange in the lungs. This would yield low oxygen saturation with retention of carbon dioxide (incorrect answers b and c) and lower pH (incorrect answers d and e). Emphysema involves dilated and dysfunctional alveoli from alveolar tissue damage, usually secondary to cigarette smoking. The hypoxia leads to tissue deoxygenation and acidosis, exacerbated by the hypercarbia (CO₂ accumulation) that distinguishes respiratory acidosis (higher bicarbonate than expected) from metabolic acidosis (very low bicarbonate, usually with low Pco₂ due to compensatory hyperventilation). The increased temperature and BPG in exercising muscle have similar effects.

The tetrameric structure of hemoglobin allows cooperative binding of oxygen in that binding of oxygen to the heme molecule of the first subunit facilitates binding to the other three. This enhanced binding is due to allosteric changes of the hemoglobin molecule, accounting for its S-shaped oxygen-saturation curve as compared with that of myoglobin (see Fig. 2 of the High-Yield Facts). At the lower oxygen saturations in peripheral tissues (Po₂ 30-40), hemoglobin releases much more oxygen (up to 50% desaturated) than myoglobin with its single polypeptide structure. The amount of oxygen released (and Co₂ absorbed as carboxyhemoglobin) is further increased by the Bohr effect—increasing hydrogen ion (H+) concentration (lowering pH) and increasing CO₂ partial pressure (PCO₂) shift the sigmoidal-shaped oxygen-binding curve for hemoglobin further to the right.

32. The answer is d. (Murray, pp 48-56. Scriver, pp 4571-4636.) Successive binding of oxygen atoms to hemoglobin progressively changes the tertiary and quaternary structure to produce cooperative kinetics and a sigmoidal oxygen-binding curve. This cooperativity does not occur with the subunits of myoglobin despite similar primary and secondary protein structure (incorrect answer b). Hemoglobin thus binds proportionately less oxygen within the capillaries of low-oxygen peripheral tissues and allows more oxygen delivery to these tissues (incorrect answer e). Isolated heme binds carbon dioxide 25,000 times more strongly than oxygen, but in myoglobin and each hemoglobin chain, a histidine group interferes with the preferred mode of carbon dioxide binding such that oxygen is favored (incorrect answer a). Oxidation of the ferrous iron in myoglobin or hemoglobin to ferric ion abolishes oxygen binding, in contrast to the case with other proteins such as cytochromes or catalase, where oxidation/reduction of iron modulates their function (incorrect answer c). Nitrates in well water inhibit methemoglobin reductase and increase the percentage of hemoglobin with ferric ion (methemoglobin). Some mutant hemoglobins such as hemoglobin M stabilize the ferric ion and produce more peripheral cyanosis.

33. The answer is c. (Murray, pp 48-56. Scriver, pp 4571-4636.

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