Fatty acids as modulators of cytochrome c oxidase in proteoliposomes

The control of cytochrome c oxidase turnover in proteoliposomes by membrane potential (Delta Psi) and by pH gradient (Delta pH) is probably kinetic in nature, and inhibition by valinomycin and stimulation by nigericin indicate that Delta pH exerts a greater influence than does an equivalent Delta Psi. Oleic acid at 100 mu M removes all Delta Psi and Delta pH control, whereas a similar concentration of palmitic acid increases turnover but does not completely abolish control. Valinomycin acts synergistically with both fatty acids, indicating that the latter can act as H+/K+ exchangers, but neither fatty acid alone markedly affects Delta pH, showing that they cannot fully mimic nigericin. Oleate, but not palmitate, diminishes Delta Psi, and can move electrophoretically as oleate anion. Submicromolar palmitic acid concentrations partly stimulate turnover in Delta Psi- and Delta pH-controlled proteoliposomes, as reported by Labonia, Muller and Azzi [(1988) Biochem. J. 254, 130-145], which might represent a direct effect on cytochrome c oxidase. The ubiquity of fatty acids in biological membranes suggests that these substances might be responsible for limiting respiratory control and enzyme activity in vivo.