NAD⁺-dependent L-lactate dehydrogenase (LDH (specifically, L-LDH or LDH-A/LDH-B depending on isoform))

NAD⁺-dependent L-lactate dehydrogenase is an oxidoreductase enzyme (EC 1.1.1.27) catalyzing the reversible interconversion of pyruvate and L-lactate, using NAD⁺ as a cofactor. In anaerobic conditions, this enzyme facilitates continued ATP production by recycling NAD⁺ for glycolysis. LDH exists as five oligomeric isoforms composed of varying combinations of LDHA (M) and LDHB (H) subunits, each encoded by separate genes and exhibiting distinct tissue distributions and kinetic properties. LDHA favors pyruvate to lactate conversion (important in muscles), while LDHB is more active in lactate to pyruvate conversion (important in heart). Because LDH is released into the bloodstream following cellular damage, serum LDH is widely used as a clinical biomarker. Aberrant LDH activity and expression are associated with cancer metabolism (Warburg effect), cardiovascular disease, and other pathological processes. Experimental inhibitors of LDH are studied as potential therapeutics in oncology and other diseases characterized by metabolic dysregulation.

Other names

Lactate dehydrogenase A (LDHA, muscle type, "M" subunit)Lactate dehydrogenase B (LDHB, heart type, "H" subunit)L-lactate dehydrogenaseLDH-ALDH-BEC 1.1.1.27

Competitive inhibition of substrate binding (e.g., pyruvate or NAD⁺ analogues); Allosteric inhibition disrupting enzyme activity; Targeting the catalytic site or essential residues involved in hydrogen transfer