Lactate dehydrogenase mechanism

Hendrickson CM, Bowden JA. 1976. In vitro inhibition of lactate dehydrogenase by insecticidal polychlorinated hydrocarbons I. Mechanism of inhibition Possible association of reduced nicotinamide adenine dinucleotide with mirex. J Agric Food Chem 24(2) 241-244. 

The principles of enzyme catalysis discussed on p. 90 can be illustrated using the reaction mechanism of lactate dehydrogenase (LDH) as an example. 

Different abortives may be formed with alternative products or substrates. Such procedures can be useful in helping to distinguish Theorell-Chance mechanisms from ordered systems with abortive complexes . In the case of lactate dehydrogenase, the E-pyruvate-NAD+ and E-lactate-NADH abortive complexes may play a regulatory roles in aerobic versus anaerobic metabolism. 

A sequential enzyme-catalyzed reaction mechanism in which two substrates react to form two products and in which there is a preferred order in the binding of substrates and release of products. Several enzymes have been reported to have this type of binding mechanism, including alcohol dehydrogenase , carbamate kinase , lactate dehydrogenase , and ribitol dehydrogenase. ... 

In the Korkes and Ochoa (11) mechanism proposed for the malo-lactic reaction (see top of next page), pyruvic acid is either a short-lived, fleeting intermediate, or it is bound to malic enzyme so that as soon as it is formed by the enzyme, it is converted to lactic acid by lactate dehydrogenase. [Both malic enzyme ( malic ) and malate dehydrogenase (de-... 

Enzymatic Reaction Mechanisms I Lactate dehydrogenase is one of the many enzymes that require NADH as coenzyme. It catalyzes the conversion of pyruvate to lactate ... 

This dimeric enzyme (subunit 35000) catalyses a reaction similar to the lactate dehydrogenase reaction, and the subunit structures of the enzymes are strikingly similar [83-85] (Fig. 20). Crystallographic [85] and other [86] evidence suggests that the reaction mechanisms are similar. The 4-pro-R hydrogen of NADH is transferred to the Re side of the oxaloacetate to give L-malate [87],... 

Do more detailed similarities of structure and mechanism accompany the broad relationships of Branden s topological analysis [72] Functionally equivalent groups around the substrate are illustrated in Fig. 35 for lactate dehydrogenase, glyceralde-... 

Many enzymes that have NAD+ or NADH as a substrate exhibit the sequential ordered mechanism. Consider lactate dehydrogenase, an important enzyme in glucose metabolism (Section 16.1.9). This enzyme reduces pyruvate to lactate while oxidizing NADH to NAD+. 

---