Regulation of Mitochondrial Respiration in Liver
In studies on the control of mitochondrial respiration carried out in the past 10 years, particular attention has been focussed on cytochrome c oxidase and the adenine nucleotide translocator as rate-controlling steps. On the basis of the observation that the first two phosphorylation sites of the respiratory chain are in near equilibrium with the extramitochondrial phosphate potential, Wilson and coworkers1–5 have concluded that regulation of respiration occurs at the cytochrome c oxidase step, the effective rate of this reaction being dependent on the extramitochondrial phosphate potential. According to this model, the adenine nucleotide translocator does not exert significant control on respiration. In contrast, Davis and coworkers6–8, Kunz and coworkers9–11, Lemasters and Sowers12, and our own group13, 14 have concluded that the adenine nucleotide trans-locator is a rate-controlling step for mitochondrial oxidative phosphorylation. The uncertainty about the precise role of the adenine nucleotide translocator and of the cytochrome c oxidase step in controlling respiration is due to the difficulty of quantifying the contribution of various steps to control of a metabolic pathway such as mitochondrial oxidative phosphorylation. Kacser and Burns15–17 and Heinrich and Rapoport18–20 have developed a theoretical framework for quantifying the amount of control that a particular step in a metabolic pathway exerts on flux through that pathway.
KeywordsThyroid Hormone Oxygen Uptake Mitochondrial Respiration Liver Mitochondrion Adenine Nucleotide
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