The effect of long-chain fatty acids on orthophosphate-adenosine 5′-triphosphate exchange activity associated with oxidative phosphorylation

Abstract

1.Various saturated and unsaturated long-chain fatty acids inhibited [32P]Pi-ATP exchange activity associated with respiratory-chain oxidative phosphorylation. Inhibition by a given concentration of long-chain fatty acid was considerably augmented by conditions which prevented fatty acid oxidation during the course of the reaction. This was accomplished by addition of various inhibitors of respiration (KCN, antimycin A, azide, or amytal) or by conducting the reaction under anaerobic conditions.2.Investigation of the effect of various saturated long-chain fatty acids at 3 · 10−5 M and in the presence of 1 mM KCN revealed that myristic, lauric, capric, palmitic, caprylic and caproic acids, in decreasing order of effectiveness, inhibited [32P]Pi-ATP exchange activity. Investigation of the effect of unsaturated fatty acids under similar conditions showed that oleic, palmitoleic, linoleic, erucic and elaidic acids, in decreasing order of effectiveness, inhibited [32P]Pi-ATP exchange activity.3.The inhibition of [32P]Pi-ATP exchange activity by long-chain fatty acids was not accompanied by significant increase in ATPase (ATP phosphohydrolase, EC 3.6.1.3) activity or evidence indicative of mitochondrial disruption.