Lactate Dehydrogenase Catalysis: Roles of Keto, Hydrated, and Enol Pyruvate

Abstract

Many carbonyl substrates of oxidoreductase enzymes undergo hydration and enolization so that these systems are partitioned between keto, hydrated (gem-diol), and enol forms in aqueous solution. Some oxidoreductase enzymes are subject to inhibition by high concentrations of substrate. For such enzymes, two questions arise pertaining to enzyme�substrate interactions: (i) which form of the system serves as the preferential and (ii) which form acts to inhibit the enzyme? Thus the relative concentrations of the forms of these systems (keto, hydrated, enol) may provide a form of metabolic control. In this light, the present article considers the reduction of pyruvate by lactate dehydrogenase in the presence of NADH. This reaction is inhibited by relatively high concentrations of pyruvate and the physiological significance of this inhibition has been a subject of controversy for many years. Summarized in this article are data from the literature pertaining to the interactions of keto, hydrated, and enol pyruvate with lactate dehydrogenase. Biochemistry instructors and their students are invited to review such pertinent articles so that they also may evaluate the possibility that the substrate inhibition of the isoenzymes in the heart muscle may be, under certain conditions, relevant as a form of metabolic control.