BCHM 3984 Module 4 Practice Questions
α-ketoglutarate dehydrogenase requires which of the following?
Both thiamin and niacin α-Ketoglutarate dehydrogenase requires five coenzymes: pyruvate dehydrogenase; thiamine pyrophosphate, lipoic acid, coenzyme A, FAD, and NAD+ .
The most potent reactive oxygen species is which one of the following?
Hydroxyl radical The hydroxyl radical is the most potent reactive oxygen species. 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 reactive oxygen species, but its potency is diminished by its reduced solubility. NO and coenzyme Q are not reactive oxygen species, although NO is a radical and will give rise to reactive nitrogen-oxygen species (RNOS).
Malate dehydrogenase requires which of the following?
Niacin Malate dehydrogenase requires NAD+ , which is synthesized from niacin.
Coenzyme A is derived from which one of the following?
Pantothenic acid Coenzyme A contains pantothenic acid, which contains the sulfhydryl group that is found in coenzyme A.
FAD is derived from which one of the following?
Riboflavin FAD contains riboflavin, which is the group that accepts electrons in the cofactor.
FMN is derived from which one of the following?
Riboflavin FMN contains riboflavin, which is the group that accepts electrons in the cofactor. FMN is flavin mononucleotide, whereas FAD is flavin adenine dinucleotide.
Pyridoxal phosphate is derived from which one of the following?
Vitamin B6 Pyridoxal phosphate contains vitamin B6 , which is the component of the cofactor that forms a covalent bond with the substrate during the course of the reaction.
A 40-year-old chronic alcoholic enters the hospital because of a variety of symptoms, including loss of feeling in his hands and feet, nystagmus, and has difficulty with his balance when walking. This patient would have difficulty catalyzing which one of the following reactions?
α-Ketoglutarate dehydrogenase The patient is exhibiting the symptoms of beriberi, caused by a vitamin B1 deficiency. Thiamine (B1) is required for oxidative decarboxylation reactions, such as those catalyzed by pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. α-Ketoglutarate dehydrogenase requires thiamine (as thiamine pyrophosphate), lipoic acid, CoASH, FAD, and NAD+ . Succinate dehydrogenase only requires FAD, fumarase has no cofactor requirement, malate dehydrogenase requires NAD , and pyruvate carboxylase requires biotin.
Consider the reaction catalyzed by fumarase: fumarate + H2O ⇌ malate. When measured in the absence of fumarase, the ΔGo´ 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?
1.0 If ΔGo ´ = 0, then −RT ln Keq = 0, because 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?
10 μM 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.
What percentage of the energy available from the oxidation of acetate is converted to ATP? Reaction Approximate ΔGo' Acetate + 2O2 -> 2Co2 + 2H2O -243 NADH + H+ + 1/2O2 -> NAD+ + H2O -53 FADH2 + 1/2O2 -> FAD + H2O -41 GTP -> GDP + Pi -8 ATP -> ADP + Pi -8
30% About 10 ATP (7.5 from NADH, 1.5 from FADH2 , and 1 from GTP) are produced 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%.
Of the total energy available from the oxidation of acetate, what percentage is transferred via the TCA cycle to NADH, FADH , and GTP? Reaction Approximate ΔGo' Acetate + 2O2 -> 2Co2 + 2H2O -243 NADH + H+ + 1/2O2 -> NAD+ + H2O -53 FADH2 + 1/2O2 -> FAD + H2O -41 GTP -> GDP + Pi -8 ATP -> ADP + Pi -8
83% In the TCA cycle, each turn of the cycle produces 2.5 NADH, 1.5 FADH , and 1 GTP. Each NADH releases 53 kcal/mol; the 2.5 NADH thus yields 132.5 kcal/mol of energy. FADH releases 61.5 kcal/mol, and GTP 8 kcal/mol. The energy captured is 132.5 + 61.5 + 8, or 202 kcal/mol. The total energy available is 243 kcal/mol, so the fraction of energy captured is 202/243, or 83%.
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 developing macular degeneration? A: Carotenoids - Yes; Flavonoids - Yes; Vitamin C - Yes; Vitamin D - No; Vitamin E - Yes B: Carotenoids - Yes; Flavonoids - No; Vitamin C - Yes; Vitamin D - Yes; Vitamin E - Yes C: Carotenoids - Yes; Flavonoids - Yes; Vitamin C - No; Vitamin D - No; Vitamin E - Yes D: Carotenoids - No; Flavonoids - No; Vitamin C - No; Vitamin D - Yes; Vitamin E - Yes E: Carotenoids - No; Flavonoids - Yes; Vitamin C - No; Vitamin D - No; Vitamin E - No F: Carotenoids - No; Flavonoids - No; Vitamin C - Yes; Vitamin D - Yes; Vitamin E - No
A Macular degeneration can come about through Oxidative damage to the macula, so the patient is trying to increase their intake of antioxidant compounds to protect against the generation of reactive oxygen species. 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 because 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 are providing for vitamin D.
A 23-year-old man was diagnosed as HIV positive 3 years ago. He has been on a variety of anti-HIV drugs since then, including AZT, along with some dideoxy compounds and HIV protease inhibitors. He recently developed muscle weakness, to the point where he had difficulty walking. This complication has come about due to which one of the following?
AZT inhibition of mitochondrial DNA polymerase AZT is a DNA chain terminator, with greatest affinity for the viral reverse transcriptase. However, mitochondrial DNA polymerase will also recognize and utilize AZT as a substrate, thereby interfering with mitochondrial DNA replication and mitochondrial division. For some patients, after prolonged AZT treatment, the reduction in mitochondrial function results in the symptoms observed in this patient. Removal of the offending agent will usually reverse this complication. AZT does not affect RNA polymerase, nor is it an uncoupler of oxidative phosphorylation. It itself does not induce release of cytochrome c from the mitochondria (a signal to start apoptosis), although if sufficient mitochondria are damaged within a cell, the cell might decide to undergo apoptosis.
Vitamin K is required for which one of the following?
Blood clotting Vitamin K is required for blood clotting because it is required for the γ-glutamate carboxylation of a variety of proteins important for the blood clotting cascade. A bleeding disorder will result from a lack of vitamin K.
An alcoholic patient 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 this patient?
Broccoli 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 scientist is conducting an experiment on isolated mitochondria in a buffered solution, in the presence of ADP. At time = 0, oxygen and succinate were added to the mitochondrial suspension, and oxygen consumption measured as a function of time. At various times after starting the experiment (labeled as 1, 2, 3, and 4 in the figure shown), different chemicals were added to the solution. Which one of the following correctly describes which chemicals were added at times 1, 2, 3, and 4? A: Antimycin, Oligomycin, Cyanide, Carbon monoxide B: Antimycin, Cyanide, Dinitrophenol, Oligomycin C: Rotenone, Oligomycin, Dinitrophenol, Cyanide D: Rotenone, Dinitrophenol, Oligomycin, Carbon monoxide E: Dinitrophenol, Rotenone, Oligomycin, Cyanide F: Dinitrophenol, Cyanide, Oligomycin, Dinitrophenol
C At time = 0, succinate is donating electrons to the electron transfer chain through complex II. Succinate is converted to fumarate, and the FADH2 generated donates the electrons to coenzyme Q via complex II. The addition of a chemical at time = 1 does not affect oxygen consumption,and the rate of oxygen consumption is the same as before adding the chemical. Rotenone inhibits at complex I and would not affect electrons being donated through complex II. Antimycin blocks the transfer of electrons from complex III to complex IV and would be expected to block electron transfer, and oxygen consumption, from electrons donated from complex II. Dinitrophenol is an uncoupler and would be expected to increase the rate of oxygen consumption when added, because the uncoupler dissipates the proton gradient and makes it easier for the electron transfer chain to pump protons out of the mitochondria. At time= 2, electron flow stops, but it restarts at time = 3, and at a faster rate. Thus, at time = 3, an uncoupler (dinitrophenol) is added. The fact that electron flow can start again, after stopping, suggests that the chemical added at time = 2 inhibited phosphorylation because phosphorylation and oxygen consumption are coupled. Inhibiting phosphorylation, via oligomycin, will block oxygen consumption without inhibiting any steps in the electron transfer chain. This is why oxygen consumption can resume again once the uncoupler is added. At time = 4, all electron flow stops and that can be due to the addition of either cyanide or carbon monoxide, both of which inhibit at complex IV.
Which component within mitochondria can exist in a radical form, and which can contribute to oxidative damage when oxygen is introduced into the system?
Coenzyme Q Coenzyme Q can accept either one or two electrons. When it accepts just one electron, it is in a radical state and can transfer that electron to oxygen by mistake, generating superoxide. The cytochromes contain an iron atom, which alternates between the ferric (+3) and ferrous (+2) states but is not considered a radical. Coenzyme A does not accept electrons to become a radical.
A firefighter is brought to the ER from the scene of a fire complaining of headaches, weakness, confusion, and difficulty 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?
Combining with cytochrome oxidase 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 by-products 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 adenine nucleotide translocase (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.
The addition of the drug atractyloside to respiring isolated mitochondria, in a lightly buffered solution containing pyruvate, ADP, and ATP, results in a cessation of oxygen consumption. The addition of which one of the following will restore oxygen consumption to these mitochondria?
Dinitrophenol The addition of atractyloside to the mitochondria blocks the adenine nucleotide translocase such that newly synthesized ATP in the mitochondrial matrix cannot exchange with ADP in the cytoplasm. This will lead to a lack of ADP in the mitochondrial matrix and an inability to synthesize more ATP. As the ATP synthase stops working, the proton gradient across the inner mitochondrial membrane increases in size (because the major reduction in gradient size is protons entering the ATP synthase to synthesize ATP) until the electron transfer chain can no longer pump protons out of the matrix because the energy generated from electron transfer is insufficient to create an even larger proton gradient. The way to restore electron flow is to add an uncoupler, which uncouples electron flow from ATP synthesis. The uncoupler destroys the proton gradient, thereby allowing proton extrusion to occur, and oxygen consumption to resume. There will still be no ATP synthesis because there is no proton gradient to drive synthesis. The addition of rotenone, succinate, oligomycin, or carbon monoxide would not help because none of those are uncouplers.
A man presents to the ER with an elevated temperature, sweats, and increased rate of breathing. He had been spraying insecticide and accidentally inhaled some of the poison. Using the insecticide on cultured cells, it was demonstrated that the rate of oxygen consumption by the cells was much greater than in the absence of the compound. This drug is acting most like which one of the following?
Dinitrophenol The insecticide is acting as an uncoupler of oxidation and phosphorylation, reducing ATP synthesis while increasing oxygen uptake (increased rate of breathing). As the uncoupler dissipates the proton gradient, the energy used to generate a gradient is lost as heat (leading to the sweating and increased temperature observed in the worker). Of the drugs listed as possible answers, only dinitrophenol (DNP) acts as an uncoupler. Cyanide and carbon monoxide interfere with cytochrome oxidase (complex IV) and block electron transfer to oxygen. Rotenone blocks electron flow from complex I to coenzyme Q, and atractyloside inhibits the ANT, leading to reduced ADP in the mitochondria and acessation of oxidative phosphorylation. Oxygen consumption would not continue in the presence of atractyloside because of the loss of ATP synthesis and the coupling of oxygen consumption and ATP production.
A man presents to the emergency room with an elevated temperature, sweats, and increased rate of breathing. He had been spraying insecticide and accidentally inhaled some of the poison. Using the insecticide on cultured cells, it was demonstrated that the rate of oxygen consumption by the cells was much greater than in the absence of the compound. This drug is acting most like which one of the following?
Dinitrophenol The insecticide is acting as an uncoupler of oxidation and phosphorylation, reducing ATP synthesis while increasing oxygen uptake (increased rate of breathing). As the uncoupler dissipates the proton gradient, the energy used to generate a gradient is lost as heat (leading to the sweating and increased temperature observed in the worker). Of the drugs listed as possible answers, only dinitrophenol (DNP) acts as an uncoupler. Cyanide and carbon monoxide interfere with cytochrome oxidase (complex IV) and block electron transfer to oxygen. Rotenone blocks electron flow from complex I to coenzyme Q, and atractyloside inhibits the adenine nucleotide translocase (ANT), leading to reduced ADP in the mitochondria and a cessation of oxidative phosphorylation. Oxygen consumption would not continue in the presence of atractyloside because of the loss of ATP synthesis and the coupling of oxygen consumption and ATP production
A 42-year-old man had experienced cramping and stiffness of muscles, coupled with severe muscle weakness in his left leg. Over time, the muscle weakness becomes more severe, and his speech has become slurred, and he has to use a wheelchair to get around. He developed swallowing difficulties, and upon diagnosis was told he had less than 2 years to live. A family history indicated that the man's father had begun to experience mild muscle weakness before he died in an automobile accident. The man's symptoms can be best explained at the molecular level by which one of the following?
Elevated levels of superoxide The man is experiencing the inherited form of ALS, which is most often caused by an inactivating mutation in superoxide dismutase. Lack of SOD activity would lead to elevated levels of superoxide, which would then, in an unknown manner, lead to a loss of motor neuron activity. Inherited mutations in NADPH oxidase, catalase, glutathione peroxidase, or myeloperoxidase have not been correlated with ALS.
A sprinter is in the midst of a 100-m race. Which one of the following reactions would be utilized under these conditions?
Glucose-1-phosphate being converted to glucose-6-phosphate Because the sprinter will be using muscle glycogen to provide glucose for energy during the race, the glycogen is converted first to glucose-1-phosphate, which is then isomerized to glucose-6-phosphate for entry into glycolysis. The reverse reaction is used for glycogen formation and would not be occurring under conditions of a sprint (answer A). The epimerization of UDP-glucose to UDP-galactose is used in the formationof lactose and not in energy generation. The conversion of fructose-6- phosphate to glucose-6-phosphate is used in gluconeogenesis and not energy production. Lactate would be produced in the muscle from pyruvate under sprinting conditions, not the other way around (lactate to pyruvate, answer choice E).
A 52-year-old man suddenly collapsed at work and was administered CPR by some coworkers until the ambulance arrived. Upon arrival at the hospital, blood test demonstrated an increased troponin I level. Tissue plasminogen activator was administered to the patient, but further damage to the affected organ resulted from this treatment. This may have happened due to which one of the following?
Increased generation of oxygen-derived radicals The patient is experiencing ischemic-reperfusion injury. The patient has suffered a heart attack, in which a region of the heart muscle has become anaerobic because of a lack of oxygen delivery. In these cells, the mitochondrial electron transfer chain is reduced because the terminal electron acceptor (oxygen) is missing. When tPA is administered to dissolve the clot that is causing the blockage of oxygen delivery to the damaged heart muscle, it allows oxygen to rapidly reenter the damaged cells. In these cells, due to the hypoxia, coenzyme Q is fully reduced in the mitochondrial membrane, and the sudden influx of oxygen leads to some accidental electron transfers to oxygen, generating the superoxide radical. This leads to increased radical damage to the already damaged heart muscle and further damage to the tissue. Cytochrome a is not released from mitochondria (there may be release of cytochrome c if the damage is sufficient, which would initiate apoptosis in the heart cells). Lactic acid levels are elevated because of anaerobic glycolysis being used to generate energy, but the high lactate levels are not contributing to further damage to the heart muscle. tPA does not have a direct effect on the activity of the TCA cycle enzymes and is not an uncoupler.
Which of the following are regulated allosterically by ADP?
Isocitrate dehydrogenase Isocitrate dehydrogenase is allosterically activated by ADP.
Which of the following catalyzes a reaction that liberates carbon dioxide?
Isocitrate dehydrogenase Isocitrate dehydrogenase removes CO2 from isocitrate to form α-ketoglutarate. There is no decarboxylation reaction associated with malate dehydrogenase (which catalyzes the reaction of malate to oxaloacetate).
Which of the following medications, given chronically, could create a physiologic response that would be a major source of free-radical production?
Isoniazid Ciprofloxacin, cimetidine, and ketoconazole all inhibit cytochrome P450. Their mode of detoxification does not require the actions of cytochrome P450. Isoniazid, 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 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?
It would remain the same An enzyme increases the rate at which a reaction reaches equilibrium but does not change the concentration of 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.
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?
Lactate 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, because of 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, 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 tissues of the eye relies almost solely on anaerobic metabolism instead of the TCA/electron transport cycle?
Lens 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 because 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 sprinter is in the midst of a 100-m race. Which one of the following sources provides the majority of the glucose for energy?
Muscle glycogenolysis Sprinting is an anaerobic activity, and the muscle will need to generate glucose at a rapid pace. Muscle contains its own glucose supply in muscle glycogen, so muscle glycogenolysis will provide the greatest amount of glucose and energy for this activity. Obtaining glucose from hepatic glycogenolysis is too slow to allow for optimal performance (liver glycogen is converted to liver glucose, exported into the circulation, then taken up by the muscle for glycolysis). Hepatic gluconeogenesis is the antithesis of what needs to occur—the liver would need to export glucose, not synthesize it. Dietary starches have to be absorbed and released by the intestinal epithelial cells to reach the circulation, another process that is too slow for efficient energy generation for sprinting. As with liver gluconeogenesis, kidney gluconeogenesis (which does occur to a small extent) is synthesizing glucose, not releasing it for the muscles to use for the activity.
A 45-year-old homeless man presents to the emergency room with peeling, scaling, red skin; diarrhea; dementia; hair loss; edema; weakness; and mouth sores. He is diagnosed as lacking a specific substance in his diet. Which one of the following is derived from this deficient substance?
NAD+ This patient has the classic symptoms of pellagra or niacin deficiency. NAD+ is derived from niacin. FMN is derived from riboflavin, coenzyme A from pantothenate, and pyridoxal phosphate from B6 . Coenzyme Q is not derived from a vitamin because it can be synthesized from acetyl-CoA.
A sprinter is in the midst of a 100-m race. The ΔG°′ for the reaction described of glucose-1-phosphate being converted to glucose-6-phosphate would be which one of the following?
Negative The ΔG°′ for the conversion of glucose-6-phosphate to glucose-1-phosphate is +1.65 kcal/mol. Because a negative ΔG°′ indicates a favorable reaction, under standard conditions, the conversion of glucose-1-phosphate to glucose-6-phosphate is favored (glycogenolysis), with a ΔG°′ of −1.65 kcal/mol. It requires energy input to synthesize glycogen.
Which of the following catalyze a reaction that utilizes FAD as a cofactor?
Neither isocitrate nor malate dehydrogenase Neither isocitrate dehydrogenase nor malate dehydrogenase utilizes FAD, which is a stronger oxidizing agent than NAD+ and is frequently used to create carbon-carbon double bonds, which NAD+ cannot do (thus, succinate dehydrogenase utilizes FAD to create the double bond found in fumarate). Conversely, NADH is a better educing agent than FADH .
Pyruvate carboxylase requires which of the following?
Neither thiamin nor niacin Pyruvate carboxylase requires biotin (which is required for most carboxylation reactions), but not NAD+ or thiamine.
Succinate dehydrogenase requires which of the following?
Neither thiamin nor niacin Succinate dehydrogenase requires FAD, which is derived from riboflavin, but neither thiamine pyrophosphate nor NAD+ .
A contestant on a TV reality show, in which the contestants had to survive off the land for an extended period of time, developed recurrent 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?
Niacin The contestant has the symptoms of pellagra, which is characterized by the four Ds (i.e., diarrhea, dermatitis, dementia, and eventual death). Pellagra is caused by 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.
Consider the running of just one cycle of the TCA cycle, in which acetyl-CoA enters the cycle, condenses with oxaloacetate to form citrate, and then the cycle regenerates oxaloacetate with the loss of two carbons as carbon dioxide. The origin of the carbon atoms that are lost as carbon dioxide is best described by which one of the following?
Oxaloacetate The two carbons that are lost as carbon dioxide when citrate goes around the cycle to reform oxaloacetate originally are derived from the oxaloacetate and not from the acetyl-CoA. The carbon dioxides are generated during the isocitrate dehydrogenase step and the α-ketoglutarate dehydrogenase step. The carbons of oxaloacetate that ultimately become carbon dioxide are carbons 1 and 4, the carboxylic acid carbons.
A scientist has developed a drug that, when added to eukaryotic cells, leads to elevated lactate levels. Analysis of mitochondrial contents also demonstrated elevated α-ketoglutarate levels in drug-treated cells. This drug may be interfering with a reaction that requires which one of the following vitamins?
Pantothenate The elevation of lactate, as well as α-ketoglutarate in the TCA cycle, suggests a defect in reactions that catalyze oxidative decarboxylations. Pyruvate would accumulate if pyruvate dehydrogenase was defective,and the increase in concentration of pyruvate would increase the production of lactate. Five cofactors are needed for oxidative decarboxylation reactions: NAD+ , FAD, lipoic acid, thiamine pyrophosphate, and coenzyme A (which is derived from pantothenicacid). The drug appears to be acting by blocking the conversion of pantothenic acid to coenzyme A. Biotin is used for carboxylation reactions, as is vitamin K. Ascorbate is utilized for proline hydroxylation, and vitamin B6 helps to catalyze a variety of reactions involving amino acids.
In which one of the following scenarios should a type 2 diabetic, 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?
Severe loss of cardiac tissue as a result of myocardial infarction Metformin tends to increase circulating blood lactate levels because of 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 becauseof metformin use will accumulate because 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 outcome. Red blood cells produce lactate, so anemia would cause reduced lactate formation. A significant weight gain would not be cause to stop taking metformin.
A long-distance runner is training, and part of the training requires running multiple sets of 800-m runs in order to increase her stamina. Energy generation by the TCA cycle is enhanced under these conditions due to which one of the following?
Stimulation of the flux through a number of enzymes by a decreased NADH/NAD+ ratio During aerobic exercise, the muscle needs to generate ATP via oxidative phosphorylation. For this to occur, NADH levels will decrease (an increase in NADH levels would inhibit the TCA cycle enzymes), leading to a decrease in the NADH/NAD ratio. Although citrate is an inhibitor of citrate synthase, if this were to occur during exercise, the TCA cycle would stop, not push forward. The activity of isocitrate dehydrogenase is inhibited (not activated) by NADH, and fumarase is not a regulated enzyme. If TCA cycle intermediates were to decrease in concentration, then the cycle would slow as well, the opposite of what is needed under conditions in which energy needs to be generated, such as during exercise.
Arsenate acts as a phosphate analog, and when an arsenio-anhydride bond is formed, it is easily hydrolyzed in water, and the bond is broken, releasing arsenate and a carboxylic acid. Which one of the TCA cycle reactions will be impacted by the presence of arsenate?
Succinate thiokinase The α-ketoglutarate dehydrogenase reaction produces succinyl-CoA, which is converted to succinate and GTP by the succinate thiokinase reaction. This reaction requires inorganic phosphate and GDP, and the initial step of the reaction is the phosphate replacing the coenzyme A on the succinate, to form a high-energy bond as succinyl phosphate. When arsenate is present, the arsenate is linked to the succinate, to form succinyl arsenate, which is rapidly hydrolyzed to form succinate and free arsenate. This blocks high-energy phosphate bond formation, and GTP will not be produced. None of the other TCA cycle enzymes utilize free inorganic phosphate as a substrate, so they will not be affected by arsenate
A 57-year-old man has begun to exhibit slurred speech, difficulty in lifting his right foot, is frequently dropping things, and complains of muscle pain in his arms and legs. His medical journey eventually takes him to a neurologist who diagnoses the disorder, at which time the patient is in a wheelchair. From the medical history, it appears as if the patient's father also exhibited similar symptoms before dying in an automobile accident. The protein that is most likely impaired in this patient is which one of the following?
Superoxide dismutase The patient has the symptoms of Lou Gehrig disease, amyotrophic lateral sclerosis. The familial form of the disease can be caused by an inherited mutation in the gene for superoxide dismutase, although the mechanism for causing the disease is not known. Although catalase and glutathione peroxidase help to protect against radical damage, they do not use superoxide as a substrate. Mutations in glutathione reductase would lead to increased oxidative damage (through an inability to regenerate reduced glutathione), but mutations in this protein have not been linked to ALS. A loss of cytochrome c oxidase activity (complex IV) would most likely be lethal in utero because it is the enzyme that converts oxygen to water in the electron transfer chain.
Dieticians encourage their vegetarian patients to squeeze lemon juice onto their green leafy vegetables. Which one of the following statements best describes the utility of this advice?
The ascorbic acid aids in the absorption of iron. Vitamin C (ascorbic acid) has three bodily functions—hydroxylation reactions, absorption of iron, and as an antioxidant. Citrus fruits are an excellent source of vitamin C. Green leafy vegetables contain iron, but very little or no vitamin B12 , D, or E. While vitamin K is in green leafy vegetables, citric acid has no role in vitamin K absorption.
Metformin is the standard first-line oral medication for type 2 diabetes. 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?
The cardiac muscle cells utilize the lactate as fuel. 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 due to the reduced gluconeogenesis occurring in the liver in the presence of metformin because lactate is a key substrate for gluconeogenesis). The cardiac muscles, with their massive amount of mitochondria, will utilizelactate 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 because 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.
A patient suffering a heart attack was brought to the emergency room. An atherosclerotic plaque had blocked a major coronary artery, preventing blood from reaching a region of her heart. As a result, in cells of the affected heart muscle, there was an increase in which one of the following?
The concentration of ADP A lack of blood flow decreased the flow of O2 to the heart, resulting in slowing the electron transport chain. The reduction in the rate of the electron transfer chain will lead to an increase in intramitochondrial NADH levels, thus slowing down the TCA cycle. A slowdown of the TCA cycle leads to a reduction in carbon dioxide production. ATP levels within the mitochondria would also drop as the ATP was transported into the cytoplasm in exchange for ADP. Because oxidative phosphorylation was blocked, the ADP that enters the mitochondria cannot be converted back into ATP, leading to an accumulation of ADP under these conditions.
A 43-year-old woman 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?
The concentration of NAD+ 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.
Which one of the following is a property of pyruvate dehydrogenase?
The enzyme requires thiamine pyrophosphate as a cofactor. 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.
A four-year-old boy has had a history of skin infections, pneumonia, nausea, vomiting, and abdominal pain. He has been on antibiotics prophylactically for the past year, but still contracts various sort of infections, both bacterial and fungal. Physical examination demonstrated hepatosplenomegaly. The boy most likely has inherited a mutation that prevents which one of the following reactions?
The formation of superoxide The boy has the symptoms of chronic granulomatosis, which, in the inherited condition, is caused by a defect in a component of NADPH oxidase. NADPH oxidase is responsible for the respiratory burst in neutrophils and produces superoxide from oxygen and NADPH. The superoxide formed helps to destroy invading bacteria and fungi. In the absence of this activity, the body has difficulty protecting itself from bacterial and fungal infections. The conversion of hydrogen peroxide to hydroxyl radicals is not enzyme catalyzed, so the loss of such conversion cannot be inherited. Mutations in superoxide dismutase (which catalyzes the conversion of superoxide to hydrogen peroxide and oxygen) can lead to ALS, but not chronic granulomatosis. The loss of glutathione reductase can lead to hemolytic anemia, but not the observed symptoms. Neutrophils do not produce hydrochloric acid. The stomach does, however, and a loss of acid production can lead to digestive disorders.
An alcoholic patient 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?
The functioning of the FMN components of complex I This patient has vitamin B2 (riboflavin) deficiency, riboflavinosis, 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.
Under cellular conditions, the aconitase reaction has a positive ΔG value, yet the TCA cycle can continue to operate. This is due to which one of the following?
The isocitrate dehydrogenase reaction has a negative ΔGo value. The cycle continues because of the very favorable isocitrate dehydrogenase reaction (with a large negative ΔGo value) reducing isocitrate levels, thereby pushing the aconitase reaction to producing more isocitrate to maintain the equilibrium ratio of 90% citrate, 6% cisaconitate, and 4% isocitrate. The aconitase is reversible, but strongly favors citrate formation. The citrate synthase reaction has a large negative ΔGo value and favors citrate formation, but the accumulation of citrate is not what allows the cycle to bypass the energetically unfavorable aconitase reaction.
The P/O ratio for FADH2 is 1.5, whereas for NADH, it is 2.5. The explanation for this difference in P/O ratios is best described by which one of the following?
The oxidation of NADH results in the extrusion of more protons than the oxidation of FADH2. When NADH donates two electrons to the electron transfer chain, 10 protons are extruded from the mitochondrial matrix because the electrons travel through the chain, and oxygen is reduced to water. Fourprotons are extruded at complex I, four again at complex III, and two protons are extruded at complex IV. It requires four protons entering the matrix to synthesize a high-energy bond, three through the ATP synthase, and one to transfer inorganic phosphate from the cytosol to the mitochondrial matrix. The 10 protons extruded divided by the 4 protons required to synthesize a high-energy bond yields a P/O ratio of 2.5 for NADH. When FADH2 donates electrons to the chain, only six protons are extruded (four at complex III and two at complex IV), thus yielding a P/O ratio of 1.5.
A man presents to the emergency room after ingesting an insecticide. His respiration rate is very low. Information from the Poison Control Center indicates that this particular insecticide binds to and completely inhibits cytochrome c. Therefore, which one of the following would occur in this man's mitochondria?
The rate of ATP synthesis would be approximately zero. If cytochrome c cannot function, all components of the electron transport chain between it and O2 remain in the oxidized state, and the components of the chain before cytochrome c are reduced. The electron transport chain will not function; O2 will not be consumed; a proton gradient will not be generated; and ATP will not be produced. NADH will not be oxidized, thereby increasing the NADH/NAD+ ratio. Owing to this increased ratio, the TCA cycle will slow down, and therefore, CO2 production will decrease.
The reactions of the TCA cycle oxidizing succinate to oxaloacetate can be described by which one of the following?
The requirement for both NAD+ and FAD Succinate is converted to oxaloacetate via the following steps: succinate to fumarate, generating FADH2 ; hydration of fumarate to malate via the addition of water; and oxidation of malate to oxaloacetate, generating NADH. FAD is, therefore, required for conversion of succinate to fumarate, and NAD is required for the conversion of malate to oxaloacetate. 3.5 moles of ATP can be generated from these reduced cofactors. Coenzyme A is not required for these reactions, and no isomerization reactions occur. GTP is produced in a previous step of the cycle, when succinyl-CoA is converted to succinate.
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?
These reactions require a coenzyme synthesized in the human from niacin (nicotinamide). 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.
Diabetes mellitus is the classic clinical process used as an example of dysregulated glucose metabolism. However, even in diabetics, glucose is still metabolized for energy. When glucose reacts with ATP to form glucose-6-P and ADP, which one of the following correctly describes this reaction?
This reaction will proceed toward product formation. Because standard free energy changes are additive, the final ΔGo (free energy) of this reaction is negative; so, the reaction proceeds toward product formation and releases energy. The rate of a reaction is not related to its free energy change. Other nucleoside triphosphates (GTP and CTP) have the same Gibb's free energy of hydrolysis as does ATP.
Vitamin A is involved in which one of the following processes?
Vision Vitamin A is required for formation of the visual pigments. Vitamin C is needed for collagen biosynthesis, vitamin D for calcium homeostasis, and vitamin K is required for the carboxylation of factors important in blood clotting.
A native Alaskan patient has yellowish orange-colored skin, but his sclera are not yellow. You learn from the patient history that the patient is a hunter and frequently eats seal and bear liver. The patient is diagnosed with an excess of an ingested substance. Which one of the following statements best describes why this skin color change occurred?
Vitamin A is fat soluble and is stored by the body in large amounts. A yellowish orange skin discoloration is a classic symptom of vitamin A poisoning. β-Carotene has a yellowish cast, and this is a precursor of vitamin A (but not vitamin D). Vitamin D is a fat soluble, but excess vitamin D does not change skin coloration, and no disease process is ascribed to high levels of vitamin D. Yellowish skin and yellow sclera usually means a high serum bilirubin. Vitamin B and vitamin C are water soluble and are stored only in limited amounts if taken in excess. Liver is the tissue that stores vitamin A.
A 43-year-old woman 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 process described in the patient, a diet high in which one of the following should be recommended?
Whole grains and meat 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.
