Studies on the metabolism of glycolyl-CoA

Abstract

Glycolyl-CoA can be formed during the course of the β-oxidation by rat liver mitochondria of 4-hydroxybutyrate. The existence of this β-oxidation has been previously supported by the occurrence of 4-hydroxybutyrate and its β-oxidation catabolites in urine from patients with 4-hydroxybutyric aciduria, an inborn error of γ-aminobutyric acid metabolism due to the deficiency of succinic semialdehyde dehydrogenase. The characteristics of the mitochondrial β-oxidation of 4-hydroxybutyrate were, in rat liver, compared with those of the mitochondrial β-oxidation of butyrate. The inhibition by malonate of the oxidation of 4-hydroxybutyrate was about twofold weaker than that of oxidation of butyrate, whereas both oxidations were abolished by preincubating the mitochondria with 1 mM valproic acid, a known inhibitor of mitochondrial β-oxidation. Mitochondria from rat kidney cortex were demonstrated to catalyse, as previously shown for hepatic mitochondria, the carnitine-dependent oxidation of 12-hydroxylauroyl-CoA. ω-Hydroxymonocarboxylyl-CoAs are thus concluded to be precursors of glycolyl-CoA also in rat kidney cortex. In addition, 3-hydroxypyruvate was found to be a precursor of glycolyl-CoA, since it was oxidized by bovine heart pyruvate dehydrogenase with a cofactor requirement similar to that of pyruvate oxidation. Glycolyl-CoA was a substrate of carnitine acetyltransferase (pigeon breast muscle). Pig heart citrate synthase was capable of catalyzing the condensation of glycolyl-CoA with oxaloacetate. The product of this reaction induced low NADH production rates dependent on the addition of porcine heart aconitase and isocitrate dehydrogenase.Key words: glycolyl-CoA, ω-hydroxymonocarboxylates, β-oxidation, 4-hydroxybutyrate, CoA-dependent 3-hydroxypyruvate oxidation, pyruvate dehydrogenase, citrate synthase, hydroxy citrate.