Textbook Reading: Biochemistry, 3rd Edition, by Voet & Voet, Chapter 22, especially p. 820-827.
Some recent articles (optional reading): T. Friedrich & B. Böttcher (2004) "The gross structure of the respiratory complex I: a Lego system," Biochim. Biophys. Acta 1608: 1-9. C. Hunte, H. Palsdottir & B. L. Trumpower (2003) "Protonmotive pathways and mechanisms in the cytochrome bc1 complex," FEBS Lett. 545: 39-46. M. Wikström & M. I. Verkhovsky (2002) "Proton translocation by cytochrome c oxidase in different phases of the catalytic cycle," Biochim. Biophys. Acta 1555: 128-132. C. R. D. Lancaster (2003) "The role of electrostatics in proton-conducting membrane protein complexes," FEBS Lett. 545: 52-60. P. Brzezinski (2004) "Redox-driven membrane-bound proton pumps," Trends in Biochem. Sci. 29: 380-387. A. R. Crofts (2004) "The cytochrome bc1 complex: Function in the context of structure," Annu. Rev. Physiol. 66: 689-733. A. Osyczka, C. C. Moser & L. P. Dutton (2005) "Fixing the Q cycle," Trends in Biochem. Sci. 30: 176-182. S. Papa, N. Capitanio, G. Capitanio & L. L. Palese (2004) "Protonmotive cooperativity in cytochrome c oxidase," Biochim. Biophys. Acta 1658: 95-105. A. Namslauer & P. Brzezinski (2004) "Structural elements involved in electron-coupled proton transfer in cytochrome c oxidase," FEBS Lett. 567: 103-110. P. C. Hinkle (2005) "P/O ratios of mitochondrial oxidative phosphorylation," Biochim. Biophys. Acta 1706: 1-11. H. Tedeschi (2005) "Old and new data, new issues: the mitochondrial DY," Biochim. Biophys. Acta 1709: 195-202. J. P. Hosler, S. Ferguson-Miller & D. A. Mills (2006) "Energy transduction: proton transfer through the respiratory complexes," Annu. Rev. Biochem. 75: 165-187. G. Brändén, R. B. Gennis & P. Brzezinski (2006) "Transmembrane proton translocation by cytochrome c oxidase," Biochim. Biophys. Acta 1757: 1052-1063. A. Y. Mulkidjanian (2005) "Ubiquinol oxidation in the cytochrome bc1 complex: Reaction mechanism and prevention of short-circuiting," Biochim. Biophys. Acta 1709: 5-34. P. Brzezinski & P. Adelroth (2006) "Design principles of proton-pumping haem-copper oxidases," Current Opin. Struct. Biol. 16: 465-472. A. R. Crofts, S. Lhee, S. B. Crofts, J. Cheng & S. Rose (2006) "Proton pumping in the bc1 complex: A new gating mechanism that prevents short circuits," Biochim. Biophys. Acta 1757: 1019-1034. A. Y. Mulkidjanian, J. Heberle & D. A. Cherepanov (2006) "Protons @ interfaces: Implications for biological energy conversion," Biochim. Biophys. Acta 1757: 913-930.
Potential Test Questions:
1.a. Summarize the Chemiosmotic theory of oxidative phosphorylation. What is the nature of the coupling between electron transfer and ATP synthesis? Why is an intact membrane required for oxidative phosphorylation? b. Describe and explain the effects of uncoupling reagents on mitochondrial respiration (oxygen consumption), on ATP synthesis, and on ATP hydrolysis. What is the mechanism of action of uncouplers? c. Write out an equation for the overall reaction catalyzed by respiratory chain complex III, including net inputs and outputs of the Q cycle.
2. Diagram and describe the effect of ADP addition on oxygen consumption by mitochondria in the presence of an excess of inorganic phosphate and an electron source (e.g., succinate). Emphasizingthermodynamicrelationships (the spontaneity of coupled reactions), explain in relation to the Chemiosmotic theory the dependence of mitochondrial respiration on availability of ADP. Why is respiration (e.g., electron transfer from succinate to oxygen) inhibited in the absence of ADP? Why does addition of ADP in the presence of Pi stimulate respiration?
