Chapter 17 The Citric Acid Cycle Matching Questions Use the following to answer questions 1-10: Choose the correct answer from the list below. Not all of the answers will be used. a) cytosol b) phosphorylation phosphorylation c) anaplerotic d) mitochondria e) cis-aconitate f) arsenite g) metabolon h) oxaloacetate i) inner membrane j) flavoproteins k) carbon dioxide l) glyoxylate cycle 1 ____________ Where does the citric acid cycle take place in the cell? cell? Ans: d Section: Introduction 2 ____________ These proteins proteins are tightly tightly associated with FAD or FMN. Ans: j Section: 17.1 3 ____________ This is the intermediate intermediate between between citrate citrate and isocitrate. Ans: e Section: 17.2 4 ____________ This is the location location of succinate dehydrogenase. Ans: i Section: 17.2 5 ____________ This TCA intermediate intermediate is both both at the beginning beginning and at the end of the the citric acid cycle. Ans: h Section: 17.2 6 ____________ This is one of the products of the citric citric acid cycle. Ans: k
Chapter 17 The Citric Acid Cycle
Section: 17.2 7 ____________ This is a name suggested for associated multienzyme complexes in metabolism. Ans: g Section: 17.2 8 ____________ This substance is toxic because it reacts with the neighboring sulfhydryl groups of dihydrolipoyl groups and blocks its reoxidation to lipoamide. Ans: f Section: 17.4 9 ____________ This type of enzyme regulation process inhibits the pyruvate dehydrogenase complex. Ans: b Section: 17.3 10 ____________ This is the name applied to metabolic reactions that replenish citric acid cycle intermediates that are depleted because they were used for biosynthesis. Ans: c Section: 17.4
Fill in the Blank Questions 11 Carbons from carbohydrate enter the citric acid cycle in the form of _______________. Ans: acetyl CoA Section: Introduction 12 In the citric acid cycle, the __________ is produced by a substrate-level phosphorylation. Ans: GTP Section: 17.2 13 E1 of the pyruvate dehydrogenase complex requires the coenzyme ________________ for proper activity. Ans: thiamine pyrophospate Section: 17.1 14 E2 of the pyruvate dehydrogenase complex contains a lipoyl group that is covalently attached to a _______________ residue of the enzyme. Ans: lysine Section: 17.1 15 _______________ is a citric acid cycle enzyme that is also an example of an iron-sulfur protein. Ans: Aconitase or succinate dehydrogenase Section: 17.2 16 The ____________ cycle is a process by which plants and some bacteria can convert twocarbon acetyl units into four-carbon units (succinate) for glucose synthesis, energy production, and biosynthesis. Ans: glyoxylate Section: 17.5
2
Chapter 17 The Citric Acid Cycle
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17 During the oxidation of isocitrate, the intermediate that is decarboxylated to form αketoglutarate is ______________________. Ans: oxalosuccinate Section: 17.2 18 In general, the citric acid cycle is inhibited under ________ (high, low) energy conditions. Ans: high Section: 17.3 19 ________________ is the first citric acid cycle intermediate to be oxidized. Ans: Isocitrate Section: 17.2 20 Beri-beri is caused by a deficiency of __________________. Ans: thiamine Section: 17.4
Multiple Choice Questions 21 The citric acid cycle is also known as the A) Krebs cycle. B) Cori cycle. C) tricarboxylic acid cycle. Ans: D Section: Introduction
D) E)
a and c. a, b, and c.
22 What molecule initiates the citric acid cycle by reacting with oxaloacetate? A) pyruvate D) All of the above. B) acetyl CoA E) None of the above. C) oxaloacetate Ans: B Section: 17.2 23 What enzyme(s) is (are) responsible for the following reaction? Pyruvate + CoA + NAD + → acetyl CoA + NADH + H + + CO2 A) acetyl CoA synthetase D) a and b B) pyruvate decarboxylase E) a, b, and c C) pyruvate dehydrogenase complex Ans: C Section: 17.1 24 What are the steps involved (in order) in the conversion of pyruvate to acetyl CoA? A) decarboxylation, oxidation, transfer to CoA B) decarboxylation, transfer to CoA, oxidation C) oxidation, decarboxylation, transfer to CoA D) oxidation, transfer to CoA, decarboxylation E) None of the above. Ans: A Section: 17.1 25 Which of the following vitamins are precursors to coenzymes that are necessary for the formation of acetyl CoA from pyruvate? A) thiamine, riboflavin, niacin, lipoic acid, and pantothenic acid B) thiamine, riboflavin, niacin, lipoic acid, pantothenic acid, and biotin C) thiamine, riboflavin, niacin, and biotin D) thiamine, riboflavin, and lipoic acid E) none of the above
Chapter 17 The Citric Acid Cycle
Ans: A
4
Section: 17.1 and Table 17.1
26 Which of the following functions as a “flexible swinging arm” when it transfers the reaction intermediate from one active site to the next? A) FAD B) NAD+ C) lipoamide D) thiamine pyrophosphate E) coenzyme A Ans: C Section: 17.1 27 Formation of citrate from acetyl CoA and oxaloacetate is a(n) _________ reaction. A) oxidation D) ligation B) reduction E) None of the above. C) condensation Ans: C Section: 17.2 28 What is/are the chemical change(s) involved in the conversion of citrate into isocitrate? A) hydration followed by dehydration D) dehydration followed by hydration B) oxidation E) a and b C) oxidation followed by reduction Ans: D Section: 17.2 29 In which reaction is GTP (or ATP) directly formed in the citric acid cycle? A) conversion of succinyl CoA to succinate B) decarboxylation of α-ketoglutarate C) conversion of isocitrate to α-ketoglutarate D) All of the above. E) None of the above. Ans: A Section: 17.2 30 In which step of the citric acid cycle is FADH 2 formed? A) the conversion of succinate to malate B) the conversion of succinate to oxaloacetate C) the conversion of succinate to fumarate D) the conversion of malate to oxaloacetate E) none of the above Ans: C Section: 17.2 31 Which of these compounds is oxidized by a multienzyme complex that requires five different coenzymes? A) D) OH H -
O2C
C
C
-
O2C
CO 2
CH2 CH
H O
B) -
O2C
CH2 CH2 C
E) -
CO 2
O CH3 C
SCoA
-
CO 2
Chapter 17 The Citric Acid Cycle
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O
C) -
O2C
Ans: B
CH2 C
-
CO 2
Section: 17.2
32 Which of the following conditions will activate pyruvate dehydrogenase kinase which catalyzes the phorphorylation and inactivation of E 1 in the pyruvate dehydrogenase complex? A) elevated concentrations of NADH and ATP B) elevated concentrations of NAD + and ADP C) Ca2+ D) insulin E) elevated concentrations of acetyl-CoA Ans: A Section: 17.3 33 Approximately how many ATP or GTP equivalents are produced during one turn of the citric acid cycle? A) 10 B) 6 C) 9 D) 12 E) None of the above. Ans: A Section: 17.2 34 In addition to pyruvate dehydrogenase, what other enzymes are key regulatory sites in the citric acid cycle? A) isocitrate dehydrogenase D) a and b B) E) a, b, and c α-ketoglutarate dehydrogenase C) citrate synthase (in bacteria) Ans: E Section: 17.3 35 The glyoxylate cycle enables plants to survive using only A) pyruvate. D) all of the above. B) acetate. E) none of the above. C) oxaloacetate. Ans: B Section: 17.4
Short-Answer Questions 36 Give the net equation of the citric acid cycle. Ans: Acetyl-CoA + 3 NAD + + FAD + GDP + Pi
→
2 CO2 + 3 NADH + 3 H + + FADH2 + GTP + CoA Section: 17.2 37 Why is the isomerization of citrate to isocitrate a necessary step of the citric acid cycle? Ans: Citrate is a tertiary alcohol that cannot be oxidized. The isomerization converts the 3° alcohol into isocitrate, which is a 2° alcohol that can be oxidized. Section: 17.2 38 List the five coenzymes that are required for the oxidative decarboxylation of pyruvate and α– ketoglutarate and give the essential nutrient (vitamin) that is required for each. Ans: 1. thiamine pyrophosphate: thiamine, vitamin B 1 2. lipoamide: lipoic acid
Chapter 17 The Citric Acid Cycle
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3. NAD +: niacin 4. FAD: riboflavin, vitamin B 2 5. coenzyme A: pantothenic acid Section: 17.1 & 17.2 39 Explain why a GTP is energetically equivalent to an ATP in metabolism. Ans: The enzyme nucleoside diphosphokinase reversibly transfers a phosphoryl group from GTP to ADP according the reaction: GTP + ADP GDP + ATP Conversly, a phosphoryl group can be transferred from ATP to a GDP forming GTP. Section: 17.2 40 Give the reaction in the citric acid cycle by which the energy is conserved in the formation of a phosphoanhydride bond by substrate level phosphorylation. Give the name of the enzyme that catalyzes this reaction and give the structures of the reactants and products of this reaction. O succinyl-CoA synthetase Ans: O 2CCH2CH2C SCoA succinyl-CoA Section: 17.2
+ GDP + P i
O2CCH2CH2CO 2 succinate
+
GTP
41 What reaction serves to link glycolysis and the citric acid cycle? Ans: Pyruvate + CoA + NAD + → acetyl CoA + NADH + H ++ CO2 Section: 17.1 42 Why is the observed electron transfer from FADH 2 to NAD+ unusual? Ans: It is unusual because the electrons are passed to the NAD + from the FADH 2. The transfer is usually in the other direction. Section: 17.1 43 What is the energy source that drives the condensation of oxaloacetate and and acetyl CoA to produce citrate? Ans: Citrate synthase catalyzes the condensation of acetyl CoA and oxalacetate to form citryl CoA. This reaction is easily reversible. The hydrolysis of the thioester of citryl CoA forms citrate and regenerates the CoA. The hydrolysis of the high energy thioester drives the reaction toward citrate. Section: 17.2 44 How does the decarboxylation of α-ketoglutatarate resemble that of pyruvate decarboxylation? Ans: Both are α-ketoacids, which are decarboxylated, and involve formation of a thioester with CoA, which has high transfer potential. The enzymatic complexes and mechanisms are similar, and the dihydrolipoyl dehydrogenase components are identical. Section: 17.1 & 17.2 45 How many ATP equivalents are produced from the total oxidation of one pyruvate to 3 CO 2. Ans: The total oxidation of one pyruvate by pyruvate dehydrogenase and the citric acid cycle produces 4 NADH, 1 FADH 2 and one GTP. 2.5 ATP are produced when two electrons are transferred from NADH to oxygen by the electron transport chain. 1.5 ATP are produced when two electrons are transferred from FADH 2 to oxygen by the electron
Chapter 17 The Citric Acid Cycle
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transport chain. Energetically, a GTP is equal to an ATP. So a total of 12.5 ATP equivalents are produced. (4 × 2.5 + 1.5 + 1 = 12.5) Section: 17.2 46 The ΔG˚′ = −21 kJ/mol for the reaction catalyzed by isocitrate dehydrogenase yet the ΔG˚′ = +29.7 kJ/mol for the reaction catalyzed by malate dehydrogenase. Both of these reactions involve the oxidation of a secondary alcohol. Give an explanation as to why the oxidation of isocitrate is so exergonic. Ans: The oxidation of isocitrate produces oxalosuccinate. The decarboxylation of oxalosuccinate produces CO 2 gas, which essentially eliminates the reverse reaction. The conversion of malate to oxaloacetate does not produce CO 2 and is endergonic. In contrast, the loss of CO 2 makes the conversion of isocitrate to α-ketoglutarate very favorable. Section: 17.2 47 How is succinate dehydrogenase unique when compared to the other enzymes in the citric acid cycle? Ans: It is the only enzyme embedded in the mitochondrial membrane, and it is directly associated with the electron transport chain. Section: 17.2 48 Are the acetyl carbons that enter the citric acid cycle the exact same carbons that leave as CO 2? Briefly explain. Ans: No, the carbons are different. The carbons that leave as CO 2 come from oxaloacetate that condensed with acetyl CoA. However, since succinate is symmetrical, and the carbons randomize, eventually all carbons are turned over. Section: 17.2 49 How does the term “mad as a hatter” realistically reflect the condition? Ans: Hatters used mercury in their craft. Frequently, the mercury would be absorbed and would react with sulfhydryls, such as those on the dihydrolipoyl groups. This resulted in neurological pathologies. Section:17.3 50 Give a sequence of metabolic reactions by which all six carbons in citrate could be obtained from two pyruvate molecules. + + Ans: NAD NADH + H O O CoA CH3C SCoA CH3C CO 2 OH CoASH CO 2 O CCH CCH CO 2
O
O CH3C
O2CCH2CCO 2
CO 2 ATP
Section: 17.1 & 17.2
ADP + Pi
2
2
CO 2
2
