Enzymic carboxylation of butyryl coenzyme A. I. Conversion of butyryl coenzyme A to 2-ethylmalonyl coenzyme A

Abstract

1. 1. The presence of an enzyme in dog skeletal and heart muscle and ox, chicken, and rat liver, which catalyzes the fixation of C 14O 2 by butyryl coenzyme A (CoA) is described. The reaction requires adenosine triphosphate (ATP) and Mn ++ or Mg ++. 2. 2. The relative rates of carboxylation of acetyl-CoA, propionyl-CoA, and butyryl-CoA in these tissues is about 1:25:3, suggesting that one enzyme—propionyl-CoA carboxylase—is involved in all three reactions. In rat liver mitochondria the rates of carboxylation of propionyl-CoA and butyryl-CoA are almost equal. 3. 3. The product of carboxylation of butyryl-CoA has been identified as 2-ethyl-malonyl-CoA. Reversibility of the carboxylation reaction was demonstrated with synthetic 2-ethylmalonyl-CoA. 4. 4. Rat liver mitochondrial extract catalyzes the synthesis of 2-ethylmalonyl-CoA from 2-ethylmalonate, adenosine triphosphate and coenzyme A. 5. 5. Methylmalonyl-CoA isomerase preparations from kidney and Propionibacterium shermanii do not isomerize 2-ethylmalonyl-CoA to either glutaryl-CoA or methylsuccinyl-CoA. 6. 6. The significance of the butyryl-CoA carboxylation reaction and the metabolism of 2-ethylmalonyl-CoA are discussed.