Differences in flux control and reserve capacity of cytochrome c oxidase (COX) in human skeletal muscle and brain suggest different metabolic effects of mild COX deficiencies.

To evaluate tissue specific control of oxidative phosphorylation by cytochrome c oxidase (COX) we determined the flux control coefficient and the metabolic reserve capacity of this enzyme in human saponin-permeabilised muscle fibers and digitonin-treated parahippocampal homogenates. In these tissue preparations it is possible to investigate mitochondrial function under conditions which are close to the in vivo situation. In the presence of NAD-dependent substrates we observed, under active state conditions, a flux control coefficient of COX over oxidative phosphorylation of 0.24 +/- 0.07 and a 1.9 +/- 0.2-fold excess capacity in human skeletal muscle fibers. In human parahippocampal gyrus we determined, under similar conditions, a flux control coefficient of COX of 0.12 +/- 0.05 and a 3.9 +/- 0.6-fold excess capacity of the enzyme. The observed difference in metabolic control can be attributed to activity differences of COX in human brain and muscle mitochondria. Our results predict stronger metabolic effects of mild COX activity deficits in human skeletal muscle than in brain tissue.