laktaattidehydrogenaasi

Laktaattidehydrogenaasi, known in English as lactate dehydrogenase (LDH), is a family of cytosolic enzymes that catalyze the reversible conversion of lactate to pyruvate with concurrent interconversion of NADH and NAD+. The enzyme is present in all aerobic and anaerobic organisms and plays a pivotal role in cellular metabolism, particularly under hypoxic conditions where it facilitates the regeneration of NAD+ to sustain glycolysis.

The LDH gene family in mammals encodes several isoenzymes (LDH-A, LDH-B, LDH-C, LDH-D and LDH-E) that assemble into tetramers of various subunit combinations determining tissue distribution and kinetic properties. LDH-A, with a high affinity for lactate, is abundant in muscle and generates pyruvate during anaerobic glycolysis, whereas LDH-B, prevalent in heart and red blood cells, favors the conversion of pyruvate to lactate. The balance between these isoforms affects metabolic flexibility and is a key factor in the Warburg effect observed in many cancers.

Clinical relevance stems chiefly from its use as a biomarker. Serum LDH activity elevates in hemolysis, myocardial infarction, liver disease, hemoglobinopathies, and various malignancies. While nonspecific, patterns of isoenzyme changes can assist in differential diagnoses. Additionally, LDH activity assays are employed in forensic biology and fisheries to assess tissue viability and metabolic state.

Structure-function studies reveal a conserved catalytic motif where a histidine residue acts as a proton shuttle, and a lysine stabilizes the nicotinamide ring of NAD+. Crystallographic analyses have yielded high-resolution structures that have guided the design of selective inhibitors, some of which are being explored as therapeutic agents in oncology and ischemic disease.