The Biosynthesis of β-Hydroxy-β-methylglutaryl Coenzyme A in Yeast

Abstract

Abstract In the presence of catalytic amounts of the β-hydroxy-β-methylglutaric acid coenzyme A-condensing enzyme of yeast, substrate amounts of acetoacetyl acyl carrier protein and acetyl coenzyme A react to form stoichiometric amounts of protein-bound β-hydroxy-β-methylglutaric acid, which is apparently β-hydroxy-β-methylglutaric acid acyl carrier protein. The condensation reaction with acetoacetyl acyl carrier protein proceeds at about one-sixth the rate observed with acetoacetyl coenzyme A. β-Hydroxy-β-methylglutaric acid coenzyme A does not undergo a transacylation reaction with acyl carrier protein, but a nonenzymatic transacylation of β-hydroxy-β-methylglutaric acid acyl carrier protein to coenzyme A does occur. These observations agree with previous suggestions that the thioester bond of the acetoacyl moiety remains intact during the condensation reaction with acetyl coenzyme A and provide a basis for unification of the so called malonate and acetate pathways of β-hydroxy-β-methylglutaric acid synthesis.