Problem 1
Energy harvest. What is the yield of ATP when each of the following substrates is completely oxidized to \(\mathrm{CO}_{2}\) by a mammalian cell homogenate? Assume that glycolysis, the citric acid cycle, and oxidative phosphorylation are fully active. (a) Pyruvate (b) Lactate (c) Fructose 1,6 -bisphosphate (d) Phosphoenolpyruvate (e) Galactose (f) Dihydroxyacetone phosphate
Problem 3
Potent poisons. What is the effect of each of the following inhibitors on electron transport and ATP formation by the respiratory chain? (a) Azide (b) Atractyloside (c) Rotenone (d) DNP (e) Carbon monoxide (f) Antimycin A
Problem 8
Cyanide antidote. The immediate administration of nitrite is a highly effective treatment for cyanide poisoning. What is the basis for the action of this antidote? (Hint: Nitrite oxidizes ferrohemoglobin to ferrihemoglobin.)
Problem 9
Currency exchange. For a proton-motive force of \(0.2 \mathrm{V}\) (matrix negative), what is the maximum [ATP]/[ADP][Pi] ratio compatible with ATP synthesis? Calculate this ratio three times, assuming that the number of protons translocated per ATP formed is two, three, and four and that the temperature is \(25^{\circ} \mathrm{C}\).
Problem 10
Runaway mitochondria 1. Suppose that the mitochondria of a patient oxidize NADH irrespective of whether ADP is present. The \(P: O\) ratio for oxidative phosphorylation by these mitochondria is less than normal. Predict the likely symptoms of this disorder.
Problem 11
An essential residue. The conduction of protons by the \(\mathrm{F}_{0}\) unit of ATP synthase is blocked by the modification of a single side chain by dicyclohexylcarbodiimide. What are the most likely targets of action of this reagent? How might you use sitespecific mutagenesis to determine whether this residue is essential for proton conduction?
Problem 12
Recycling device. The cytochrome \(b\) component of \(Q\) -cy tochrome \(c\) oxidoreductase enables both electrons of \(\mathrm{QH}_{2}\) to be effectively utilized in generating a proton-motive force. Cite another recycling device in metabolism that brings a potentially dead end reaction product back into the mainstream.
Problem 13
Crossover point. The precise site of action of a respiratorychain inhibitor can be revealed by the crossover technique. Britton Chance devised elegant spectroscopic methods for determining the proportions of the oxidized and reduced forms of each carrier. This determination is feasible because the forms have distinctive absorption spectra, as illustrated in the adjoining graph for cytochrome \(c .\) You are given a new inhibitor and find that its addition to respiring mitochondria causes the carriers between NADH and \(\mathrm{QH}_{2}\) to become more reduced and those between cytochrome \(c\) and \(\mathrm{O}_{2}\) to become more oxidized. Where does your inhibitor act?
Problem 14
Runaway mitochondria 2. Years ago, it was suggested that uncouplers would make wonderful diet drugs. Explain why this idea was proposed and why it was rejected. Why might the producers of antiperspirants be supportive of the idea?
Problem 15
Coupled processes. If actively respiring mitochondria are exposed to an inhibitor of ATP synthase, the electron-transport chain ceases to operate. Why?
