Book Questions Flashcards
An uncoupled of oxidative phosphorylation such as dinitrophenol
A. Inhibits respiration and ATP synthesis
B. Allows electron transport to proceed without ATP synthesis
C. Inhibits respiration without impairment of ATP synthesis
D. Specifically inhibits cytochrome-b
E. Acts as a competitive inhibitor of NAD+ requiring reactions in the mitochondria
The electron transport chain produces an H+ gradient across the inner mitochondrial membrane that drives ATP synthesis. An uncoupler short-circuits that gradient, so that the energy contained is converted to heat rather than being used for ATP synthesis. However, the electron transport chain itself is not inhibited by uncouplers.
James Gillray, the grandfather of all political cartoonists, created an illustration of an inflamed and swollen joint of the big toe into which a fire-breathing demon digs its fangs and talons. This piece of art, called The Gout, depicted the severe pain associated with a condition of the same name. Under the influence of allopurinol, the concentration of which compound would decrease in a patient suffering with this condition?
A. Xanthine B. Hypoxanthine C. Xanthosine D. Guanine E. Uric Acid
E − Allopurinol suicide inactivates xanthine-oxidase and thus prevents the conversion of xanthine into uric acid. The concentrations of xanthine, hypoxanthine, xanthosine, and guanine would actually increase.
A, B, C, D Allopurinol suicide inactivates xanthine-oxidase and thus prevents the conversion of xanthine into uric acid. The concentrations of xanthine, hypoxanthine, xanthosine, and guanine would actually increase.
In mitochondria treated with the uncoupled dinitrophenol (DNP), how many molecules of ATP are derived from the oxidation of one molecule of NADH A. 0 B. 1 C. 2 D. 3 E. 6
A − In an uncoupled system, the proton gradient generated from the oxidation of NADH and FADH2 is short-circuited, allowing protons to flow back from the intermembrane space into the matrix without passing through the ATP synthase. The energy conserved in the proton gradient is converted to heat, rather than being used to generate ATP.
B, C, D, E See explanation for A.
The following are the properties of three GI proteases
Enzyme |OptimumpH | Molecular Mass (kDa) | Type
1 2.0 35 Soluble
2 6.8 109 Membrane bound
3 8.0. 24. Soluble
Which of the three enzymes, pepsin, trypsin and alanine (Ala)-aminopeptidase correspond to 1, 2 and 3?
A. 1 (pepsin), 2 (trypsin), 3 (Ala-aminopeptidase)
B. 1 (pepsin), 2 (Ala-aminopeptidase), 3 (trypsin)
C. 1 (trypsin), 2 (pepsin), 3 (Ala-aminopeptidase)
D. 1 (trypsin), 2 (Ala-aminopeptidase), 3 (pepsin)
E. 1 (Ala-aminopeptidase), 2 (trypsin), 3 (pepsin)
B − 1 has a pH-optimum in the strongly acidic range, which corresponds to the stomach, so this is pepsin. 2 and 3 have pH-optima near neutral, corresponding to the environment found in the intestine. Of those, 3 is a soluble enzyme, he
What is the effect of an “œuncoupler” on metabolism?
A The formation of ATP continues, but oxidation of TCA cycle intermediates ceases.
B ATP formation ceases because TCA cycle activity is inhibited.
C Mitochondrial metabolism is blocked.
D The movement of ATP and ADP across mitochondrial membranes is impaired.
E ATP formation ceases, but O2 consumption increases
E − Uncouplers “œshort-circuit” the proton gradient across the inner mitochondrial membrane and thereby deprive the ATP synthase (complex V) of its energy source. Examples include dinitrophenol, pentachlorophenol, certain drugs such as aspirin or zidovudine (AZT), and metabolites such as bilirubin. Thermogenin (UCP1) is a protein that forms a proton channel in the mitochondria of brown adipose tissue. The high [ADP] and low [ATP] in the presence of uncouplers lead to increased glycolysis, TCA cycle and complex I to IV activity, and hence oxygen consumption.
You are on a group hiking tour in South Tirol (Europe). You had a brilliant if slightly strenuous day out and a nice group dinner in the hotel, consisting of ricotta cheese and spinach-filled potato dumplings with tossed salad and fried eggs, accompanied by a local red wine. Two hours later you are called to one of your companions, who is feeling sick. You find an elderly lady, pale, clammy, in obvious distress. She is complaining about abdominal pain, vomiting, belching, diarrhea, and flatulence. After arranging transport to a local polyclinic, you find that temperature, vital signs, EKG, serum analysis, chest and abdominal X-ray, and ultrasound are normal. What is the most likely diagnosis?
A Acute myocardial infarction B Appendicitis C Overexertion D Foodborne illness E Lactose incompatibility
E − All other causes are excluded by the patient’s presentation and by the exam results. The signs and symptoms fit those of someone who is lactose intolerant. Lactose-intolerant patients usually know about the problems they get when ingesting lactose and will avoid doing so. Problems arise when their food is prepared by others, and milk products “œhide” in this case the spinach turned out to contain ricotta cheese. Advising the preparer of special dietary needs unfortunately does not always prevent these problems.
In aerobic metabolism, most of the high-energy phosphate is generated by
A glycolysis acting on glycogen and generating lactate.
B glycolysis acting on glucose and generating pyruvate.
C the pyruvate dehydrogenase reaction.
D the TCA cycle.
E protons passing through the Fo–F1 complex.
E − By far, the most ATP is made by oxidative phosphorylation in which electron transport generates a pH gradient that in turn drives the Fo–’F1 ATPase. Glycolysis and the TCA cycle contribute only two ATP and two guanosine triphosphates (GTPs), respectively, per glucose.
A Glycolysis acts on glucose, not glycogen. Lactate is produced in anaerobic, not aerobic, glycolysis. The former also produces only two molecules of ATP per molecule of glucose. Most of the chemical energy contained in the glucose molecule is still in the two lactate molecules produced, which are therefore used for gluconeogenesis as soon as the oxygen supply improves.
Chymotrypsin is a serine protease, with Ser-195, His-57, and Asp-102 forming the catalytic triad. In serine proteases, the ring nitrogen of histidine’™s side chain in the catalytic triad acts as a proton acceptor during the enzymatic reaction sequence. If the pH were lowered below the p Ka of the His-57 side chain, what would happen to the enzymatic activity?
A The enzyme would be activated because His-57 needs to be protonated to be active.
B The enzyme would be activated because His-57 needs to be deprotonated to be active.
C The enzyme would be inactivated because His-57 needs to be protonated to be active.
D The enzyme would be inactivated because His-57 needs to be deprotonated to be active.
E There would be no effect because His-57 can fulfill its role in both the protonated and deprotonated state.
D. − Because the ring nitrogen of histidine (His) in the catalytic triad of serine proteases acts as a proton acceptor during the enzymatic reaction sequence, it needs to be unprotonated to begin with. If the pH is lowered below its pKa, the His side chain would be constantly protonated and hence unable to function.
The presence of an electrochemical gradient of protons across the inner mitochondrial membrane is required for the production of which metabolite?
A ATP B H2O2 C FADH2 D O2 E NADH + H+
A − Phosphorylation of ADP to ATP requires energy derived from the potential energy of the proton gradient when protons pass back through ATP synthase.
The reaction catalyzed by which enzyme of the TCA cycle results in phosphorylation at the substrate level?
A Succinate dehydrogenase B alpha-Ketoglutarate dehydrogenase C ATP synthase D Citrate synthase E Succinyl CoA synthetase
E − Succinyl CoA synthetase actually works in reverse and catalyzes the breakdown of succinyl CoA into succinate and CoA. The chemical energy of succinyl CoA’™s thioester bond is used to phosphorylate GDP to GTP (in equilibrium with ATP) in animals, whereas ATP is produced directly in bacteria and plants.
Coenzymes are small organic molecules that are often required in catalytic enzymes. They assist in catalysis by providing functional groups on which reactions can occur. Each coenzyme helps catalyze a specific type of reaction for a given class of substrates. The coenzyme involved in the biochemical transfer of methyl, formyl, or hydroxymethyl groups from one molecule to another is a derivative of
A biotin B pyridoxine C lipoic acid D folic acid E ascorbic acid
D − Folic acid plays a major role in one-carbon metabolism. The derivative, N5 -methyltetrahydrofolate, is used for the synthesis of methionine from homocysteine, in a reaction requiring vitamin B12. Another derivative, N10-formyltetrahydrofolate, is used in the biosynthesis of purines, contributing carbons 2 and 8 to the purine ring system. N5, N10-methylenetetrahydrofolate is used by serine hydroxymethyl transferase to transfer hydroxymethyl groups between serine and glycine.
Inosine 5’-monophosphate (IMP) is the initial product of purine nucleotide anabolism. Which nucleotides are subsequently synthesized from IMP, each in two enzymatic steps?
A AMP and GMP B AMP and OMP C dATP and dGTP D UTP and CTP E XMP and CMP
A − AMP (adenosine monophosphate) and GMP (guanosine monophosphate) are the purine nucleoside monophosphates synthesized from IMP in two enzymatic steps.
Cytochrome-c oxidase (complex IV)
A is inhibited by rotenone.
B is the terminal enzyme of the mitochondrial electron transport chain.
C binds oxygen, resulting in the formation of hydrogen peroxide
D contains two atoms of zinc/heme-a.
E can be reduced by cytochrome-b
B − In the electron transport chain, protons and electrons (in effect, but not mechanistically) from different sources are first collected on CoQ, then separated in complex III (cytochrome-c reductase). The protons are released into the intermembrane space. The electrons are transferred via cytochrome-c onto complex IV, were molecular oxygen, four electrons and four protons (from the mitochondrial matrix) form two molecules of water.
A 35-year-old man was rushed to the emergency room because he was unconscious. He was an experienced runner and had participated in a marathon race (42 km/26.1 miles). It was a cloudy day, and the organizers had provided service stations at regular intervals on the track where isotonic drinks were served. Celebrating his fifth place in the race with his friends, the patient was drinking his third glass of champagne when he suddenly collapsed. Which immediate intervention could save the life of this patient?
A Ringer/lactate, intravenous (IV) B Insulin IV C Glucose IV D Blood clot dissolvers E Oxygen mask
C − After ~ 30 km (18.6 miles) into a marathon race, even well-trained athletes have used up their glycogen stores. They continue to run on fatty acids and ketone bodies. The reduced rate of ATP production is experienced as “œhitting the wall.” Blood glucose levels in this situation are maintained by gluconeogenesis. This is required given that brain, erythrocytes, and kidney absolutely depend on glucose for fuel. When the patient drank alcohol after this strenuous exercise, he blocked gluconeogenesis and hence his only remaining source of blood glucose, resulting in a (life-threatening) hypoglycemic coma.
A 2-year-old girl is transferred to the metabolic unit of a state pediatric hospital because of failure to thrive and severe fasting hypoglycemia with neurological sequelae. A physical exam reveals hepatomegaly. Laboratory: hyperlipidemia and impaired liver and kidney function. A transcutaneous liver biopsy reveals the accumulation of excessive amounts of glycogen. The most likely diagnosis is
A Conn syndrome B Adrenoleukodystrophy (ALD) C von Gierke disease D Alzheimer disease E Dubin-Johnson syndrome
C − This patient has von Gierke disease (glycogen storage disease Ia), marked by the accumulation of glycogen in the liver and hepatomegaly. It is caused by a defect of glucose-6-phosphatase in the liver endoplasmic reticulum. As a result, the liver cannot release glucose into the bloodstream to keep blood glucose concentrations constant during fasting, for example, at night. This affects the organs that rely on glucose for their catabolic needs (brain, erythrocyte, kidney). At the same time, high concentrations of glucose-6-phosphate in hepatocytes stimulate glycogen synthesis, leading to glycogen accumulation and hepatomegaly.
Which of the following energy-producing activities occurs in cytosol?
A Tricarboxylic acid cycle
B beta-Oxidation
C Glycolysis
D Oxidative phosphorylation
C − Glycolysis, also called Embden-Meyerhof-Parnas pathway, occurs in the cytosol. In this pathway a glucose molecule (with six C atoms) is broken down to two molecules of pyruvate (three C atoms each). The chemical energy liberated in this process is used to form two molecules of ATP from ADP and Pi.
A 1-year-old girl is brought to a family physician because of concerns about her development. She had an uncomplicated birth in a developing country at term. The mother reports that her daughter is not achieving normal milestones for a baby of her age. She also reports an unusual “mousy” odor of her urine and some hypopigmentation of skin and hair. On exam, the girl shows muscle hypotonia and microcephaly. To the physician’s surprise, a test for phenylalanine hydroxylase activity comes back normal. Her metabolic deficiency might also affect the synthesis of which of the following hormones?
A Serotonin B Thyroxine C Calcitriol D Pregnenolone E Progesterone
A − The patient is suffering from a rare form of phenylketonuria (PKU) caused by a deficiency of dihydrobiopterin reductase. This affects phenylalanine, tyrosine, and tryptophan hydroxylase, and hence the conversion of phenylalanine to tyrosine, tyrosine to dopamine, and tryptophan to serotonin.
Lipids are the primary constituents of cellular membranes. They can be oxidatively damaged when free radicals are allowed to persist within the membrane, especially those containing polyunsaturated fatty acids. Such damage can lead to the loss of membrane integrity and the formation of mutagenic or carcinogenic moieties. Many vitamins can act as antioxidants; however, not all are protective against membrane damage. Which of the following functions primarily as an antioxidant to prevent polyunsaturated fatty acids from undergoing peroxidation?
A Vitamin A
B Vitamin D
C Vitamin E
D Vitamin K
C − The compounds that comprise the vitamin E family, gamma- and alpha-tocopherol, contain long hydrophobic tails that promote insertion into cellular membranes. Here they function as antioxidants, scavenging free radicals, including the reactive oxygen species (ROS) often formed as by-products of the electron transport chain, and protecting cellular components (e.g., polyunsaturated fatty acids) from unregulated, noncatalyzed oxidation.
A 6-month-old male infant is admitted to the emergency room with vomiting, lethargy, and irritability. Diagnostic tests reveal plasma ammonium levels of 200 $\mu$M. The mother reveals that one of her male siblings died in infancy after a similar episode, although she herself has never had such an episode. Based on the high ammonium levels and the family history, the physician suspects that the patient has a deficiency in ornithine transcarbamoylase (OTC), an X-linked disorder. To test this diagnosis, the physician orders additional tests on levels of particular metabolites in the blood plasma and urine. Which of the results below support the diagnosis of OTC deficiency?
A High levels of orotic acid B High levels of citrulline C High levels of fumarate D Low levels of oxaloacetate E Low levels of glutamine and alanine
A − A deficiency in OTC results in a buildup of carbamoyl phosphate in the mitochondria of hepatocytes. The excess carbamoyl phosphate diffuses into the cytosol, where it can be converted to orotic acid in the pyrimidine biosynthetic pathway. Orotic acid levels increase because the subsequent step in purine synthesis depends on phosphoribosyl pyrophosphate (PRPP), which becomes depleted under these conditions. High levels of orotic acid in the urine, combined with hyperammonemia, are characteristic of OTC deficiency.
Monosaccharides may be linked together via glycosidic bonds to create disaccharides, oligosaccharides, and polysaccharides. In each of these, the individual monosaccharides that comprise the entire unit may or may not be the same. Among the sundry monosaccharides found in nature, glucose is perhaps one of the most ubiquitous. Which one of the following carbohydrates contains a monosaccharide unit other than glucose?
A Glycogen B Cellulose C Maltose D Lactose E Starch
D − Most notably found in milk, lactose is a disaccharide formed via condensation of galactose and glucose through a beta-1,4 glycosidic linkage. The enzyme beta-D-galactosidase (lactase) is required to cleave lactose into its individual subunits so that absorption can occur. Lack of this enzyme in the digestive system (alactasia) is the primary cause of lactose intolerance.
Cholestyramine exerts its hypocholesterolemic effect by binding and preventing uptake of which of the following?
A Cholesterol B Triacylglycerols C Lipoproteins D Bile acids E Cholesterol esters
D − Cholestyramine is a polystyrene resin with quaternary amino groups attached. By binding bile acids, cholestyramine prevents their enterohepatic circulation and promotes their removal with feces. This causes the liver to convert more cholesterol to new bile salts which lowers the plasma cholesterol level.
You are working on a research project to elucidate the reaction mechanism of an enzyme. You think that a particular serine (Ser) residue in the protein is required for catalytic activity. To test this hypothesis, you want to genetically replace this Ser by another amino acid, and then test whether the enzyme is still active. Which amino acid would you choose to replace the Ser?
A Threonine (Thr) B Alanine (Ala) C Tryptophan (Trp) D Glutamic acid (Glu) E Histidine (His)
B − Ala looks very much like Ser, except that the OH-group that makes Ser reactive is replaced by hydrogen. Thus, it forms a perfect control in this situation
Beta-Oxidation of an odd-chain fatty acid produces several two-carbon and one three-carbon molecules. The latter enters the TCA cycle in the form of which compound?
A Citrate B Isocitrate C alpha-Ketoglutarate D Succinyl CoA E Malate
D − Beta-Oxidation of an odd-chain fatty acid gives several molecules of acetyl CoA and one molecule of propionyl CoA. Propionyl CoA is also produced from the amino acids threonine, methionine, valine, and isoleucine. It is converted into succinyl CoA via propionyl CoA carboxylase (biotin-dependent), methylmalonyl CoA racemase, and methylmalonyl CoA mutase (vitamin B12–“dependent). Failure of the latter reaction leads to methylmalonic aciduria, either because of the inability to activate vitamin B12 (which manifests as acidosis and anemia) or because of a defect in the enzyme itself (which manifests as acidosis only). A defect in propionyl CoA carboxylase leads to propionic acidemia with ketoacidosis and protein intolerance.
An 8-year old girl presents with the following symptoms: onset of osteoporosis, ectopia lentis (lens detachment), and mild mental retardation. The patient was diagnosed with homocystinuria. A treatment regimen was prescribed that included dietary restriction of a particular essential amino acid and dietary supplements of vitamin B12 and folic acid. Which amino acid was restricted, and what biosynthetic reaction would be affected by the vitamin supplements?
A Methionine; enhance the conversion of homocysteine to methionine
B Cysteine; enhance the conversion of homocysteine to cysteine
C Glycine; enhance the conversion of serine to glycine
D Serine; inhibit the conversion of serine to glycine
E Cysteine; increase the absorption of cystine
A − Homocystinuria occurs due to a block in the biosynthetic pathway from homocysteine to cysteine. This results in a buildup of excess blood plasma levels of homocysteine, and in homocystinuria. As methionine is a precursor to homocysteine (through the production and utilization of S-adenosylmethionine), restricting the dietary levels of methionine reduces homocysteine levels. The vitamin supplements enhance the conversion of homocysteine to methionine because this reaction, which uses a folic acid derivative, is catalyzed by homocysteine methyltransferase. This enzyme requires cobalamin, a vitamin B12–’derived cofactor, for its activity. It is recommended that dietary restriction of methionine and vitamin supplements be used together in the treatment of homocystinuria. The levels of the essential amino acid methionine in the diet should be relatively low so that methionine will be used preferentially in protein synthesis, and the vitamin supplements will be useful in prompting the rapid conversion of homocysteine (once it is formed) to methionine, to prevent the excess buildup of homocysteine.
A student at the Metropolitan School of Nursing had a persistent cough, for which she visited her primary care doctor. She was given an inhaler to ease her symptoms, but she received no diagnosis or definitive treatment. Two weeks later, one of her lab instructors, a 48-year-old man without relevant previous history, also developed a runny nose and paroxysmal coughs ending in a noisy inspiratory stridor, with posttussive emesis. This got so bad that he sought help in the Metropolitan Mercy Hospital. Physical exam: temperature 37.4°C, respiratory rate 45/min, pulse 150 beats/min, blood pressure 102/49 mm Hg, and an oxygen saturation rate of 90%. Studies: interstitial opacities with peribronchial wall thickening on chest X-ray, respiratory secretions positive for Bordetella pertussisin polymerase chain reaction (PCR). The patient was treated with inhaled epinephrine and albuterol plus a 5-day course of azithromycin. The school informed all students, faculty, and staff of their exposure to Bordetella and suspended clinical training activities until all involved had obtained prophylactic treatment according to the Centers for Disease Control and Prevention guidelines, supervised by the state’s health authority. The production of which of the following second messengers would be higher than normal in the patient’s lung epithelial cells?
A cAMP B cGMP C Ca2+ D Diacylglycerol E IP3
A − Pertussis toxin adenosine diphosphate (ADP) ribosylates Gi$ \alpha $, preventing GDP/GTP exchange and thus inhibition of adenylate cyclase. Bordetella infections claim the lives of some 400,000 children worldwide each year; without mandatory immunization, this would be much worse. Weakening protection from childhood immunization creates a reservoir of susceptible adults; these may spread the infection to infants and elderly, in whom it is particularly dangerous. Presentation of these infections in adults may be unusual.
Which readily available intermediate from glycolysis is used as a direct precursor for the synthesis of the glycerol moiety of triacylglycerols?
A Pyruvate B 3-Phosphoglycerate C Glycerol 3-phosphate D Phosphoenolpyruvate E Dihydroxyacetone phosphate
E − Dihydroxyacetone phosphate (DHAP) is reduced to glycerol-3-phosphate in mitochondria of hepatocytes and adipocytes by glycerol-3-phosphate dehydrogenase and then acylated to produce lysophosphatidic acid.
