Pyruvate Dehydrogenase, Substrate Specificity and Product Inhibition

Abstract

Studies with intact mitochondria and with soluble pyruvate dehydrogenase indicate that pyruvate and α‐ketobutyrate are oxidized by the same enzyme (pyruvate dehydrogenase), while α‐ketovalerate is oxidized by a different enzyme. Pyruvate and α‐ketobutyrate have about the same affinity for the enzyme, but pyruvate is oxidized at a much higher rate. Acetyl‐CoA and propionyl‐CoA both behave as competitive inhibitors to CoA. The K i for both is slightly higher than the K m for CoA. Accordingly the enzyme is only moderately inhibited by a high acetyl‐CoA/CoA ratio. NADH behaves mainly as a competitive inhibitor to NAD. The K i is significantly lower than the K m for NAD. Accordingly the enzyme is strongly inhibited by a high NADH/NAD ratio. The significance of these properties of the enzyme for the regulation of the activity of pyruvate dehydrogenase in vivo is discussed.