Effects of nitric oxide and peroxynitrite on the cytochrome oxidase K(m) for oxygen: implications for mitochondrial pathology.

This review summarises current knowledge about the effect of oxygen on cytochrome oxidase activity in vitro and in vivo. Cytochrome oxidase normally operates above its K(m) for oxygen in vivo. However, decreases in the intracellular oxygen concentration (hypoxia) under physiological extremes, or during pathophysiology, can cause mitochondrial respiration to become oxygen limited. Inhibitors that raise the enzyme's K(m) will induce oxygen limitation under apparently normoxic conditions. It is known that the concentrations of nitric oxide and peroxynitrite are raised in a number of pathophysiological conditions. These compounds are capable of reversibly and irreversibly raising the cytochrome oxidase K(m) for oxygen. Therefore, measurements of cell and mitochondrial respiration in vitro that fail to systematically vary oxygen through the range of physiological concentrations are likely to underestimate the effects of nitric oxide and peroxynitrite in vivo.