Diacetyl: a new substrate in the overall reaction of the pyruvate dehydrogenase complex

Pig heart pyruvate dehydrogenase complex (pyruvate: lipoamide oxidoreductase (decarboxylating and acceptor-acetylating), EC 1.2.4.1) catalyzes the decomposition of diacetyl to acetate, acetyl-CoA and produces reduced NAD+ with 1:1:1 stoichiometry. The reaction rate with diacetyl is approximately 7.1% of that with pyruvate. The Km value for diacetyl was found to be 0.46 mM. Acetoin and acetaldehyde inhibit the pyruvate dehydrogenase-catalyzed reaction of diacetyl with Ki values of 0.91 mM and 0.48 mM, respectively. Inhibition patterns show that they are competitive inhibitors versus diacetyl. Acetate, as product, does not inhibit the enzymatic decomposition of diacetyl. Diacetyl is not only an alternative substrate in the pyruvate dehydrogenase reaction, but a competitive inhibitor versus pyruvate with a Ki value of 0.43 mM.