Influence of octanoate on the rate of oxidative phosphorylation and the associated extramitochondrial ATP/ADP ratios studied with isolated rat liver mitochondria oxidizing pyruvate.
The regulation of oxidative phosphorylation by the extramitochondrial ATP/ADP ratio was investigated with pyruvate (malate) or pyruvate (malate) plus octanoate as substrates in experiments with isolated rat liver mitochondria. Steady states in the supply of non-saturating substrate concentrations and the activity of oxidative phosphorylation were adjusted by means of a perifusion technique which is based on immobilisation of mitochondria on glass filters. Michaelis-Menten parameters of the pyruvate oxidation in active state respiration were determined both in the absence and presence of octanoate. Octanoate yielded only slight Km value increase, whereas the maximal rate of pyruvate oxidation was diminished to one half. Therefore, it is concluded that the inhibitory action of octanoate on pyruvate oxidation comes close to a non-competitive mechanism. The inhibitory effect of octanoate is completely reversible. When a change in substrate supply was accomplished by substituting pyruvate (malate) plus octanoate for pyruvate (malate) under conditions of a simulated extramitochondrial energy demand, respiration was stimulated and ATP/ADP ratios generated outside mitochondria were shifted to a higher value. Two different responses of the mitochondrial respiration to the extramitochondrial ATP/ADP ratios were found as a function of the presence or absence of octanoate.
D000244:Adenosine Diphosphate / Q000032:analysis*; D000255:Adenosine Triphosphate / Q000032:analysis*; D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats
D002210:Caprylates; D011773:Pyruvates; D000244:Adenosine Diphosphate; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; C031492:octanoic acid