Thealpha‐oxidation system of brain microsomes. Cofactors foralpha‐hydroxy acid decarboxylation

Abstract

A one-carbon degradation of long-chain fatty acids, which was found to occur in the brains of rats in vivo, has been investigated in a brain microsomal fraction in vitro. Decarboxylation of the α-hydroxy acid, a possible intermediate product between the substrate and the next shorter acid, in the presence of brain microsomal fraction was enhanced by ATP, NAD, and a dialyzable fraction from the supernatant fraction. The cofactor requirement for the decarboxylation of the α-hydroxy acids provided by the dialyzable fraction can be met by several reducing agents or ferrous ion. The effectiveness of several possible cofactors for the decarboxylation of α-hydroxy acids has been evaluated. It is concluded that the decarboxylation of the α-hydroxystearic acid may be a reaction with molecular oxygen catalyzed by an oxidase or oxygenase that requires iron in the reduced state for activity. The possibility that the reaction proceeds through an α-keto acid intermediate has been examined in the light of new knowledge of the conditions for decarboxylation. It is concluded that a short-lived keto acid is a possible intermediate. Definitive proof however is lacking because the characteristics of the reaction require that such an intermediate decarboxylate without dissociating from the enzyme.