Problems

1. Oxidation-Reduction Reactions The NADH dehydrogenase complex of the mitochondrial respiratory chain promotes the following series of oxidation-reduction reactions, in which Fe3+ and Fe2+ represent the iron in iron-sulfur centers, Q is ubiquinone, QH2 is ubiquinol, and E is the enzyme:

For each of the three reactions catalyzed by the NADH de-hydrogenase complex, identify (a) the electron donor, (b) the electron acceptor, (c) the conjugate redox pair, (d) the reducing agent, and (e) the oxidizing agent.

2. All Parts of Ubiquinone Have a Function In electron transfer, only the quinone portion of ubiquinone undergoes oxidation-reduction; the isoprenoid side chain remains unchanged. What is the function of this chain?

3. Use of FAD Rather Than NAD+ in Succinate Oxidation All the dehydrogenases of glycolysis and the citric acid cycle use NAD+ (E'° for NAD+/NADH is -0.32 V) as electron acceptor except succinate dehydrogenase, which uses covalently bound FAD (E'° for FAD/FADH2 in this enzyme is 0.050 V). Suggest why FAD is a more appropriate electron acceptor than NAD+ in the dehydrogenation of succinate, based on the E'° values of fumarate/succinate (E'° = 0.031), NAD+/NADH, and the succinate dehydrogenase FAD/FADH2.

4. Degree of Reduction of Electron Carriers in the

Respiratory Chain The degree of reduction of each carrier in the respiratory chain is determined by conditions in the mitochondrion. For example, when NADH and O2 are abundant, the steady-state degree of reduction of the carriers decreases as electrons pass from the substrate to O2. When electron transfer is blocked, the carriers before the block become more reduced and those beyond the block become more oxidized (see Fig. 19-6). For each of the conditions below, predict the state of oxidation of ubiquinone and cytochromes b, c1, c, and a + a3.

(a) Abundant NADH and O2, but cyanide added

(b) Abundant NADH, but O2 exhausted

(c) Abundant O2, but NADH exhausted

(d) Abundant NADH and O2

5. Effect of Rotenone and Antimycin A on Electron Transfer Rotenone, a toxic natural product from plants, strongly inhibits NADH dehydrogenase of insect and fish mitochondria. Antimycin A, a toxic antibiotic, strongly inhibits the oxidation of ubiquinol.

(a) Explain why rotenone ingestion is lethal to some insect and fish species.

(b) Explain why antimycin A is a poison.

(c) Given that rotenone and antimycin A are equally effective in blocking their respective sites in the electron-transfer chain, which would be a more potent poison? Explain.

6. Uncouplers of Oxidative Phosphorylation In normal mitochondria the rate of electron transfer is tightly coupled to the demand for ATP. When the rate of use of ATP is relatively low, the rate of electron transfer is low; when demand for ATP increases, electron-transfer rate increases. Under these conditions of tight coupling, the number of ATP molecules produced per atom of oxygen consumed when NADH is the electron donor—the P/O ratio—is about 2.5.

(a) Predict the effect of a relatively low and a relatively high concentration of uncoupling agent on the rate of electron transfer and the P/O ratio.

(b) Ingestion of uncouplers causes profuse sweating and an increase in body temperature. Explain this phenomenon in molecular terms. What happens to the P/O ratio in the presence of uncouplers?

(c) The uncoupler 2,4-dinitrophenol was once prescribed as a weight-reducing drug. How could this agent, in principle, serve as a weight-reducing aid? Uncoupling agents are no longer prescribed, because some deaths occurred following their use. Why might the ingestion of uncouplers lead to death?

7. Effects of Valinomycin on Oxidative Phosphoryla-tion When the antibiotic valinomycin is added to actively respiring mitochondria, several things happen: the yield of ATP decreases, the rate of O2 consumption increases, heat is released, and the pH gradient across the inner mitochon-drial membrane increases. Does valinomycin act as an uncou-pler or an inhibitor of oxidative phosphorylation? Explain the experimental observations in terms of the antibiotic's ability to transfer K+ ions across the inner mitochondrial membrane.

8. Mode of Action of Dicyclohexylcarbodiimide (DCCD) When DCCD is added to a suspension of tightly coupled, actively respiring mitochondria, the rate of electron transfer (measured by O2 consumption) and the rate of ATP production dramatically decrease. If a solution of 2,4-dinitro-phenol is now added to the preparation, O2 consumption returns to normal but ATP production remains inhibited.

(a) What process in electron transfer or oxidative phos-phorylation is affected by DCCD?

(b) Why does DCCD affect the O2 consumption of mitochondria? Explain the effect of 2,4-dinitrophenol on the inhibited mitochondrial preparation.

(c) Which of the following inhibitors does DCCD most resemble in its action: antimycin A, rotenone, or oligomycin?

9. Compartmentalization of Citric Acid Cycle Components Isocitrate dehydrogenase is found only in the mitochondrion, but malate dehydrogenase is found in both the cytosol and mitochondrion. What is the role of cytosolic malate dehydrogenase?

10. The Malate-a-Ketoglutarate Transport System

The transport system that conveys malate and a-ketoglu-tarate across the inner mitochondrial membrane (see Fig. 19-27) is inhibited by n-butylmalonate. Suppose n-butyl-malonate is added to an aerobic suspension of kidney cells using glucose exclusively as fuel. Predict the effect of this inhibitor on (a) glycolysis, (b) oxygen consumption, (c) lactate formation, and (d) ATP synthesis.

11. Cellular ADP Concentration Controls ATP Formation Although both ADP and Pi are required for the syn

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Essentials of Human Physiology

Essentials of Human Physiology

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Responses

  • julia roth
    When electron transfer is blocked, the carriers before the block become more reduced and?
    7 years ago
  • shona
    When azaid or cyanide is added to actively respiring mitochondria?
    7 years ago
  • THOMAS
    What is the advantage of using FAD as an electron acceptor rather than NAD ?
    6 years ago

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