Oxidative phosphorylation stoichiometry

Hinkle, P.C., Kumar, M. A., Rasetar, A., Harris, D.L. (1991). Mechanistic stoichiometry of mitochondrial oxidative phosphorylation. Biochemistry 30, 3576-3582. 

Hinkle PC et al Mechanistic stoichiometry of mitochondrial oxidative phosphorylation. Biochemistry 1991 30 3576. 

One view to explain different P/O ratios for different classes of organisms is to consider variability in both the molecular mechanism as well as the stoichiometry of proton transport and ATP synthesis with the source of the enzyme [67]. However, considering our molecular mechanism and the energetics of the oxidative phosphorylation process, we believe that a universality in the mechanistic, kinetic and thermodynamic characteristics of the system is operative. 

We saw in Chapter 14 that the energy yield from the production of two molecules of pyruvate from one molecule of glucose in glycolysis is 2 ATP and 2 NADH. In oxidative phosphorylation (Chapter 19), passage of two electrons from NADH to 02 drives the formation of about 2.5 ATP, and passage of two electrons from FADH2 to 02 yields about 1.5 ATP. This stoichiometry allows us to calculate the overall yield of ATP from the complete... 

TABLE 16-1 Stoichiometry of Coenzyme Reduction and ATP Formation in the Aerobic Oxidation of Glucose via Glycolysis, the Pyruvate Dehydrogenase Complex Reaction, the Citric Acid Cycle, and Oxidative Phosphorylation... 

Hinkle, P. C., A. Kumar, A. Resetar, and D. L. Harris, Mechanistic stoichiometry of mitochondrial oxidative phosphorylation. Biochem. 30 3576, 1991. Measurements of P-to-O ratios and a discussion of the amount of ATP synthesized during the oxidation of glucose. 

Nitrate respiration can support the synthesis of ATP, while proton pumping has been quantified for several physiological substrates. Stoichiometries of about 4H+/NO, and 2H+/N03" have been found for L-malate and formate, and succinate, D-lactate and glycerol respectively. There is evidence that about one mole of ATP is synthesized by oxidative phosphorylation per mole of nitrate reduced.1440... 

Rossi, C.S. and Lehninger, A. L., 1964, Stoichiometry of respiratory stimulation, accumulation of Ca++ and phosphate, and oxidative phosphorylation in rat liver mitochondria, J. Biol. Chem. 239,... 

We can now estimate how many molecules of ATP are formed when glucose is completely oxidized to GO2. The number of ATP (or GTP) molecules formed in glycolysis and the citric acid cycle is unequivocally known because it is determined by the stoichiometries of chemical reactions. In contrast, the AT P yield of oxidative phosphorylation is less certain because the stoi chiometries of proton pumping, ATP synthesis, and metabolite-transport processes need not be integer numbers or even have fixed values. As stated earlier, the best current estimates for the number of protons pumped out of the matrix by NADH-Q oxidoreductase, Q-cytochrome c oxidoreductase, and cytochrome c oxidase per electron pair are four, two, and four, respectively. The synthesis of a molecule of ATP is driven by the flow of about three protons through ATP synthase. An additional proton is consumed in transporting ATP from the matrix to the cytoplasm. Hence, about 2.5 molecules of cytoplasmic ATP are generated as a result of the flow of a pair of electrons from NADH to O2. For electrons that enter at the level of Q-cytochrome c oxidoreductase, such as those from the oxidation of succinate or cytoplasmic NADH, the yield is about 1.5 molecules of ATP per electron pair, Hence, as tallied in Table 18.4, about 30 molecules of ATP are formed... 

The implications of the different stoichiometries for the overall P/0 ratios are obvious. If the proton gradient is the only and necessary intermediate in oxidative phosphorylation, the theoretical P/0 ratio can be calculated from the H " /O and H /ATP ratios. The original experiments agreed with the long-accepted P/O ratios of 3, 2 and 1 for NAD-linked substrates, succinate and cytochrome c, respectively. The more recent findings may not always agree with these accepted values [123]. 

---