On the Mechanism of Translocation of Pyruvate and Other Monocarboxylic Acids in Rat‐Liver Mitochondria

Abstract

Pyruvate equilibrates, like other carboxylic acids, across the membrane of rat‐liver mitochondria according to the transmembrane pH difference. Comparison of the rate of pyruvate, acetoacetate and acetate efflux from mitochondria as well as a study of the effect of mersalyl and N‐ethylmaleimide on this process, show that the diffusion of pyruvic and acetoacetic acid across the mitochondrial membrane is carrier‐mediated. The process might consist of pyruvate (acetoacetate) hydroxyl ion exchange‐diffusion or of pyruvic acid (acetoacetic acid) uniport. On the contrary acetic acid appears to diffuse freely across the membrane. The initial rate of the net pyruvate uptake by rat liver mitochondria follows saturation kinetics. The increase of the external pH of the medium as well as the addition of acetoacetate inhibit competitively pyruvate uptake. Pyruvate uptake is inhibited by mersalyl and N‐ethylmaleimide. Mitochondria1 [14C]pyruvate exchanges with unlabelled pyruvate and acetoacetate but not with other monocarboxylates, Pi and citric‐acid cycle intermediates. The pyruvate‐pyruvate and pyruvate‐acetoacetate exchanges follow saturation kinetics and exhibit the same V but different Km values. Both the exchanges are inhibited by mersalyl, but not by N‐ethylmaleimide. It is concluded that pyruvate translocation across the mitochondrial membrane is mediated by a specific transport system. Copyright © 1974, Wiley Blackwell. All rights reserved