The inhibition of L-3-hydroxyacyl-CoA dehydrogenase by acetoacetyl-CoA and the possible effect of this inhibitor on fatty acid oxidation

Acetoacetyl-CoA was found to strongly inhibit the dehydrogenation of L-3-hydroxybutyryl-CoA catalyzed by L-3-hydroxyacyl-CoA dehydrogenase from pig heart. The inhibition constant (K_i) was determined to be 7.7 × 10^?6 M, a value which is similar to the K_m value of 12 × 10^?6 M obtained for acetoacetyl-CoA in its NADH-dependent reduction catalyzed by the same enzyme. A suggested ordered BiBi mechanism for this enzyme, with NAD binding to the enzyme first, explains the observed noncompetitive nature of this inhibition. The possible effect of this inhibition on fatty acid oxidation is discussed.