Specific, reversible inactivation of yeast β-hydroxy-β-methylglutraryl-CoA reductase by CoA

A partially purified preparation of β-hydroxy-β-methylglutaryl-CoA reductase from baker's yeast is shown to be inactivated by incubation with low concentrations of free CoA. This inactivation is highly specific for the intact CoA molecule, is time-dependent, and is not reversed by the addition of excess substrate. Reversal is possible, however, by extensive dialysis. The apparent inactivating effect of thioesters such as acetyl-CoA and propionyl-CoA can be explained by the amount of free CoA liberated from the thioesters through enzymatic hydrolysis. β-Hydroxy-β-methylglutaryl-CoA reductase thus joins a group of enzymes (α-isopropylmalate synthase, homocitrate synthase and, possibly, N-acetylglutamate synthase) which have three features in common: they are associated with the mitochondria, they control acetyl-CoA utilizing pathways, and they are inactivated by CoA.