Chapter 5 - Generation of ATP from Metabolic Fuels and Oxygen Toxicity Flashcards
Consider the reaction catalyzed by fumarase: fumarate + H2O malate
When measured in the absence of fumarase, the ΔGoº' for this reaction is 0 kcal/mol (neglecting any terms associated with H2O). The equilibrium constant for this reaction would therefore be which one of the following? (A) 0 (B) 0.5 (C) 1.0 (D) 10.0 (E) 50.0
The answer is C. If ΔGº’ = 0, then–RT ln Keq = 0, since ΔGº’ =–RT ln Keq. For–RT ln Keq to be equal to 0, the ln Keq must be 0, which means that Keq = 1 (the natural log of 1 = 0).
Consider the reaction catalyzed by fumarase: fumarate + H2O malate
Fumarase was added to a solution that initially contained 20 μM fumarate. After the establishment of equilibrium, the concentration of malate was which one of the following? (A) 2 μM (B) 5 μM (C) 10 μM (D) 20 μM (E) 50 μM
The answer is C. From the answer to Question 1, we know that Keq = 1 = [Malate]/[Fumarate] = X/(20–X). Therefore, (20–X) = X, 20 = 2X, and X = 10 μM.
Reaction / Approximate ΔGº’ (kcal/mol)
Acetate + 2 O2 → 2 CO2 + 2 H2O / –243 NADH + H+ + 1⁄2 O2 → NAD+ + H2O / –53 FADH2 + 1⁄2 O2 → FAD + H2O / –41 GTP → GDP + Pi / –8 ATP → ADP + Pi / –8  Of the total energy available from the oxidation of acetate, what percentage is transferred via the TCA cycle to NADH, FADH2, and GTP? (A) 38% (B) 42% (C) 81% (D) 86% (E) 100%
The answer is D. In the TCA cycle, each turn of the cycle produces 3 NADH, 1 FADH2,
and 1 GTP. Each NADH releases 53 kcal/mol; the 3 NADH thus yield 159 kcal/mol of energy. FADH2 releases 41 kcal/mol, and GTP 8 kcal/mol. The energy captured is 159 + 41 + 8, or 208 kcal/mol. The total energy available is 243 kcal/mol, so the fraction of energy captured is 208/243, or 86%.
Reaction / Approximate ΔGº’ (kcal/mol)
Acetate + 2 O2 → 2 CO2 + 2 H2O / –243 NADH + H+ + 1⁄2 O2 → NAD+ + H2O / –53 FADH2 + 1⁄2 O2 → FAD + H2O / –41 GTP → GDP + Pi / –8 ATP → ADP + Pi / –8
What percentage of the energy available from the oxidation of acetate is converted to ATP? (A) 3% (B) 30% (C) 40% (D) 85% (E) 100%
The answer is B. About 10 ATP (7.5 from NADH, 1.5 from FADH2, and 1 from GTP) are pro- duced by the TCA cycle (10 × 8 kcal = 80 kcal). The percentage of the total energy available from oxidation of acetate that is converted to ATP is 80/243, or 33%.
A genetic mutation caused the cellular concentration of an enzyme to increase 100-fold for a biochemical reaction. Therefore, the equilibrium constant for the reaction catalyzed by the enzyme would change in which one of the following ways?
(A) It would decrease two-fold.
(B) It would remain the same.
(C) It would increase in proportion to the
enzyme concentration.
(D) It would change inversely with the enzyme
concentration.
(E) It would decrease 100-fold.
The answer is B. An enzyme increases the rate at which a reaction reaches equilibrium but does not change the concentration of the reactants and products at equilibrium; that is, the Keq is not affected by an enzyme, so a change in enzyme concentration will have no effect on the Keq.
Consider the section of the TCA cycle in which isocitrate is converted to fumarate. This segment of the TCA cycle can be best described by which one of the following?
(A) These reactions yield 5 moles of high- energy phosphate bonds per mole of isocitrate.
(B) These reactions require a coenzyme synthesized in the human from niacin (nicotinamide).
(C) These reactions are catalyzed by enzymes located solely in the mitochondrial membrane.
(D) These reactions produce 1 mole of CO2 for every mole of isocitrate oxidized.
(E) These reactions require GTP to drive one of the reactions.
170
The answer is B. In the conversion of isocitrate to fumarate, 2 CO2, 2 NADH (which contains niacin), 1 GTP, and 1 FADH2 are produced. A total of approximately 7.5 ATP are generated. The enzymes for these reactions are all located in the mitochondrial matrix except succinate dehydrogenase, which is an inner mitochondrial membrane protein. GTP is not required in any of the reactions but is produced in the conversion of succinyl-CoA to succinate.
In the TCA cycle, a role for thiamine pyrophosphate is which one of the following?
(A) To accept electrons from the oxidation of pyruvate and α-ketoglutarate
(B) To accept electrons from the oxidation of isocitrate
(C) To form a covalent intermediate with the α-carbon of α-ketoglutarate
(D) To form a thioester with the sulfhydryl group of CoASH
(E) To form a thioester with the sulfhydryl group of lipoic acid
The answer is C. Thiamine pyrophosphate is involved in the making and breaking of carbon- carbon bonds. It is a necessary cofactor for oxidative decarboxylation reactions, in which a carbon-carbon bond is broken and carbon dioxide is released. Mechanistically, thiamine pyrophosphate forms a covalent intermediate with the α-carbon of an α-keto acid substrate, which, in the TCA cycle, is α-ketoglutarate. Thiamine pyrophosphate is not involved in redox reactions, or in thioester formation.
Which one of the following is a property of pyruvate dehydrogenase?
(A) The enzyme contains only one polypeptide chain.
(B) The enzyme requires thiamine pyrophosphate as a cofactor.
(C) The enzyme produces oxaloacetate from pyruvate.
(D) The enzyme is converted to an active form by phosphorylation.
(E) The enzyme is activated when NADH levels increase.
The answer is B. Pyruvate dehydrogenase converts pyruvate to acetyl-CoA. It contains multiple subunits: a dehydrogenase component that oxidatively decarboxylates pyruvate, a dihydrolipoyl transacetylase that transfers the acetyl group to coenzyme A, and a dihydrolipoyl dehydrogenase that reoxidizes lipoic acid. Thiamine pyrophosphate, lipoic acid, coenzyme A, NAD+, and FAD serve as cofactors for these reactions. In addition, a kinase is present that phosphorylates and inactivates the decarboxylase component. Acetyl-CoA and NADH activate this kinase, thus inactivating pyruvate dehydrogenase. A phosphatase dephosphorylates the decarboxylase subunit, thereby reactivating pyruvate dehydrogenase.
Which one of the following components of the electron transport chain only accepts electrons, and does not donate them? (A) Cytochrome b (B) Oxygen (C) Coenzyme Q (D) FMN (E) Cytochrome C1
The answer is B. Under physiological conditions, oxygen is the terminal electron acceptor in the electron transport chain, and water will not donate electrons to other substrates to regener- ate oxygen. The cytochromes, FMN, and coenzyme Q both accept and donate electrons during the course of electron flow through the electron transport chain.
Which one of the following tissues of the eye relies almost solely on anaerobic metabolism instead of the TCA/electron transport cycle?
(A) Cornea
(B) Lens
(C) Ciliary muscle
(D) Retina
(E) All of the tissues of the eye use only
anaerobic glycolysis as an energy source.
The answer is B. Aerobic metabolism requires an O2 supply. Oxygen is usually obtained from the blood, which is circulating through the blood vessels. However, transparent tissue cannot have an extensive network of blood vessels since these would create opacities that would block the transmission of light. The cornea is exposed to air and gets its oxygen by diffusion from air. The lens has no capillaries and is not exposed to the air, so it utilizes anaerobic metabolism. Glucose and lactate diffuse from and into aqueous and vitreous humor. The ciliary muscle and retina have extensive blood vessel systems, and can carry out oxidative phosphorylation in order to generate energy.
A 43-year-old female has been on a “grapefruit and potatoes” diet for several months in an effort to lose weight. She now complains of a rash
covering most of her body, a large, beefy tongue, nausea and diarrhea, and some confusion.
Which one of the following cofactors or enzyme complexes would be most affected by this condition?
(A) The concentration of NAD+
(B) The concentration of FAD
(C) The concentration of coenzyme Q
(D) The functioning of the FMN components
of complex I
(E) The functioning of the cytochrome-containing components of complex III
The answer is A. This patient has the classic symptoms of pellegra, a vitamin B3 (niacin) deficiency. NAD+ is derived from niacin. Pellagra leads to the four Ds–dermatitis, dementia, diarrhea, and death. Riboflavin is the precursor for both FAD and FMN. Coenzyme Q is synthesized from acetyl-CoA, and its levels would not be affected as much as those of NAD+. Heme is synthesized from succinyl-CoA and glycine, and a reduction in heme levels would lead to an anemia and not the symptoms as described for this patient.
A 43-year-old female has been on a “grapefruit and potatoes” diet for several months in an effort to lose weight. She now complains of a rash
covering most of her body, a large, beefy tongue, nausea and diarrhea, and some confusion.
To reverse the symptoms described in the patient, a diet high in which one of the following should be recommended? (A) Green, leafy vegetables (B) Whole grains and meat (C) Citrus fruits (D) Orange and yellow vegetables (E) Chocolate cake
The answer is B. While green, leafy vegetables are rich in other B vitamins, whole grains, meats, fish, and liver are the best sources of niacin. Citrus fruits are high in vitamin C. Orange and yellow vegetables are high in vitamin A. Chocolate cake is high in flavonoids, an antioxidant, fats, and carbohydrates.
An alcoholic presents with swelling and fissuring of the lips, cracking at the angles of the mouth, red eyes, and an oily, scaly rash of his scrotum.
Which one of the following cofactors of enzyme complexes would be most affected by this condition? (A) The concentration of NAD+ (B) The concentration of NADP+ (C) The concentration of coenzyme Q (D) The functioning of the FMN components of complex I (E) The functioning of the cytochrome- containing components of complex III
The answer is D. This patient has vitamin B2 (riboflavin) deficiency, ariboflavinosis, as indicated by the symptoms displayed by him. Both FAD and FMN require vitamin B2 to be produced. NAD+ and NADP+ are derived from niacin. Coenzyme Q is derived from acetyl-CoA, and vitamin B2 is not needed in the synthesis of the heme ring, which is derived from succinyl-CoA and glycine.
An alcoholic presents with swelling and fissuring of the lips, cracking at the angles of the mouth, red eyes, and an oily, scaly rash of his scrotum.
Which of the following foods would best help reverse the symptoms described in the above patient? (A) Broccoli (B) Carrots (C) Grapefruits (D) Wheat (E) Chocolate cake
The answer is A. Dark green vegetables, especially broccoli, meats, and dairy products are all high in riboflavin. Carrots are high in vitamin A, grapefruits in vitamin C, and whole grains in niacin. Chocolate cake is high in flavonoids, an antioxidant, fats, and carbohydrates.
A firefighter is brought to the emergency room (ER) from the scene of a fire complain- ing of headaches, weakness, confusion, and difficulty in breathing. His skin and mucous membranes appear very pink/red. The causative agent of these symptoms inhibits electron transport and oxidative phosphorylation by which one of the following mechanisms?
(A) Uncoupling of electron transport and phosphorylation
(B) Combining with NADH dehydrogenase
(C) Combining with cytochrome oxidase
(D) Inhibiting an adequate supply of ADP
(E) Combining with coenzyme Q
The answer is C. The symptoms experienced by the firefighter could be caused by either cyanide or carbon monoxide, both of which inhibit cytochrome c oxidase. Both carbon monoxide and cyanide are byproducts of fuel oxidation, and would be generated during a fire. The firefighter most likely inhaled smoke that contained one or both of these compounds. Both agents will block the reduction of oxygen to water, thereby halting the electron transfer chain and oxidative phosphorylation. Neither agent is an uncoupler, nor do they block the ANT (so ADP levels will not be decreased). Rotenone, a fish poison, complexes with NADH dehydrogenase (complex I) to inhibit electron flow from complex I to coenzyme Q. Neither cyanide nor carbon monoxide will bind to coenzyme Q and block its ability to either accept or donate electrons.
A patient is undergoing an appendectomy under general anesthesia (succinylcholine and an inhaled anesthetic) when she begins to develop muscle rigidity, tachycardia, and hyperthermia. Which of the following best describes the mechanism of this process?
(A) Uncoupling of electron transport and phosphorylation
(B) Inhibition of NADH dehydrogenase
(C) Inhibition of cytochrome oxidase
(D) Inhibiting an adequate supply of ADP
(E) Combining with coenzyme Q
The answer is A. The patient is experiencing malignant hyperthermia, which is similar in symptoms to the uncoupling of the electron transfer chain from ATP synthesis. Succinylcholine and several inhaled anesthetics can act as uncouplers of electron transport in susceptible individuals. An inhibition of complex I (NADH dehydrogenase), or cytochrome oxidase, would block both electron flow and ATP synthesis, and muscle rigidity and hyperthermia would not result. The same is true if coenzyme Q were prevented from accepting and donating electrons. An uncoupler will not lead to a decrease in ADP levels as ATP cannot be synthesized under these conditions, and ADP levels would be expected to increase.
A patient is in septic shock and his tissues are poorly perfused and oxygenated. The major end product of glucose metabolism in these tissues will be an accumulation of which one of the following? (A) Pyruvate (B) Acetyl-CoA (C) Lactate (D) Urea (E) Citrate
The answer is C. Without oxygen, aerobic metabolism cannot function, so the electron transfer chain will stop (without oxygen, cytochrome oxidase cannot remove electrons from the chain to reduce oxygen to water). ATP synthesis in the mitochondria will stop because of the coupling of oxidation and phosphorylation. The TCA cycle will stop because of the accumulation of NADH in the mitochondria (as the electron transfer chain is fully reduced, owing to the lack of oxygen, NADH cannot donate electrons to a reduced complex I), and NADH inhibits key enzymes of the TCA cycle. However, the tissues still need energy, and so they use anaerobic glycolysis to generate ATP. The end product, pyruvate, is converted to lactate to regenerate NAD+ such that glycolysis can continue. An accumulation of lactate (which is a metabolic dead end) can lead to lactic acidosis in the patient.
Which one of the following cell types cannot utilize the TCA cycle or electron transport chain? (A) Brain (B) Red blood cells (C) Liver (D) Kidney (E) Heart
The answer is B. Cellular respiration occurs in the mitochondria. Red blood cells lack mitochondria, and can only utilize anaerobic glycolysis for energy production. The brain, liver, kidney, and heart cells contain mitochondria, and can carry out oxidative phosphorylation, as well as anaerobic glycolysis.
Metformin is the standard first-line oral medication for Type 2 diabetes. The use of the drug has the potential side effect of lactic acidosis. Which of the following explains why this lactic acid buildup is rarely seen clinically?
(A) The red blood cells utilize the lactate as fuel.
(B) The renal cell utilizes the lactate as fuel.
(C) The cardiac muscle cells utilize the lactate
as fuel.
(D) The large, voluntary muscle groups utilize
the lactate as fuel.
(E) The lactate directly enters the TCA cycle to
be oxidized.
The answer is C. Metformin can increase glucose uptake by tissues and lead to increased lactate formation. In addition, metformin, through unknown mechanisms, appears to block lactate uptake by the liver (this could occur because of the reduced gluconeogenesis occurring in the liver in the presence of metformin, as lactate is a key substrate for gluconeogenesis). The cardiac muscles, with their massive amount of mitochondria, will utilize lactate as fuel and
can overcome a lactate buildup from therapeutic doses of metformin. It is only in the rare case (about 1 in 10,000) that metformin treatment will lead to lactic acidosis. Lactate does not enter the TCA cycle to be oxidized, as it first has to be converted to pyruvate, then to acetyl-CoA before it can enter the cycle. Red blood cells generate lactate, but do not utilize it as a fuel. Kidney cells, and other muscles, do not utilize lactate to an appreciable extent as a fuel, as compared to the heart muscle.
In which one of the following scenarios should a patient with Type 2 diabetes, who is taking metformin for glucose control, be advised to discontinue the metformin owing to an increased risk of lactic acidosis resulting from continuation of the metformin?
(A) Severe anemia
(B) Early pyelonephritis
(C) Severe loss of cardiac tissue from a myo-
cardial infarction
(D) Severe tear of the quadriceps muscle
(E) Significant weight gain
The answer is C. Metformin tends to increase circulating blood lactate levels owing to reduced use of lactate by the liver for gluconeogenesis, which is inhibited in the presence of metformin. The excess lactate, however, can be used by the heart as an energy source, which reduces circulating lactate levels. If the loss of cardiac muscle cells (and their mitochondria) is significant due to a myocardial infarction, the elevated lactate due to metformin use will accumulate since it is no longer being metabolized by the heart. This could lead to lactic acidosis, which may be fatal. Lactate can also accumulate in renal failure; however, none of the other conditions listed will lead to renal failure. Pyelonephritis usually does not lead to renal failure. Torn muscles may cause myoglobinuria, and this may lead to renal failure, but it would be an uncommon out- come. Red blood cells produce lactate, and so anemia would cause reduced lactate formation. A significant weight gain would not be the cause to stop taking metformin.
The most potent ROS is which one of the following? (A) Hydrogen peroxide (B) Superoxide (C) Hydroxyl radical (D) Nitric oxide (E) Coenzyme Q
The answer is C. The hydroxyl radical is the most potent ROS. It creates chain reactions that produce lipid peroxides and organic radicals. Hydrogen peroxide is not a radical, but it can generate hydroxyl radicals through interactions with transition metals. Superoxide is a potent ROS, but its potency is diminished by its reduced solubility. NO and coenzyme Q are not ROS, although NO is a radical, and will give rise to reactive nitrogen–oxygen species (RNOS).
Using Internet sources, a patient has developed his own diet plan in an attempt to prevent macular degeneration. For breakfast every morning, he has poached eggs, orange and carrot juice, and red wine. Which of the following in his diet can potentially protect against the patient develop- ing macular degeneration?

Carotenoids / Flavonoids / Vitamin C / Vitamin D / Vitamin E
(A) Yes / Yes / Yes / No / Yes (B) Yes / No / Yes/ Yes / Yes (C) Yes / Yes / No / No / Yes (D) No / No / No / Yes / Yes (E) No / Yes / No / No / No (F) No / No / Yes / Yes / No
The answer is A. Macular degeneration can come about through oxidative damage to the macula, so the patient is trying to increase his intake of antioxidant compounds to protect against the generation of ROS. There are no sources of vitamin D in the patient’s diet. Carotenoids, found in the carrot juice, are antioxidants. Flavonoids, another potent antioxidant, are found in wine. Orange juice contains vitamin C, another antioxidant. Vitamin E, a very potent antioxidant, is found in egg yolks. The role of vitamin D as an antioxidant is controversial, as its primary role is to maintain calcium homeostasis, although there are some reports of it being utilized as an antioxidant. In either event, none of the patient’s dietary sources is providing for vitamin D.
Which of the following medications, given chronically, could create a physiologic response that would be a major source of free-radical production?
(A) Ciprofloxacin
(B) Isoniazide
(C) Cimetidine
(D) Ketaconazole
(E) None of these drugs has the potential to
increase free-radical formation.
The answer is B. Ciprofloxacin, cimetidine, and ketaconazole all inhibit cytochrome P450. Their mode of detoxification does not require the actions of cytochrome P450. Isoniazide, however, induces cytochrome P450 formation as a means of oxidizing the drug to remove it from the body. Cytochrome P450 enzymes are a major source of free-radical production that can occur when electrons are accidentally leaked from reactions and react with molecular oxygen.
A contestant on a TV reality show, in which the contestants had to survive off the land for an extended period of time, developed recur- rent diarrhea, dermatitis, and had trouble remembering things. These symptoms could be brought about due to the lack of which one of the following in the contestant’s diet? (A) Niacin (B) Thiamine (C) Riboflavin (D) Vitamin C (E) Vitamin D
The answer is A. The contestant has the symptoms of pellagra, which is characterized by the four Ds (i.e., diarrhea, dermatitis, dementia, and eventual death). Pellagra is due to a lack of niacin in the diet. A thiamine deficiency will lead to beriberi; a riboflavin deficiency to ariboflavinosis; a vitamin C deficiency to scurvy; and a vitamin D deficiency to rickets. Only pellagra would yield the symptoms observed by the patient.
