What is the Function of Lactate Dehydrogenase (LDH)?
Lactate dehydrogenase (LDH) is an oxidoreductase enzyme that catalyzes the reversible conversion of pyruvate to lactate with concomitant interconversion of NADH to NAD+ during anaerobic glycolysis. 1, 2
Primary Biochemical Function
LDH serves as the terminal enzyme in the anaerobic glycolysis pathway, enabling cells to continue producing ATP when oxygen supply is inadequate. 1, 3 The enzyme catalyzes the following reversible reaction:
- Pyruvate + NADH + H+ ⇌ Lactate + NAD+ 2
- This reaction regenerates NAD+, which is essential for glycolysis to continue in the absence of oxygen 3
Metabolic Roles Beyond Anaerobic Conditions
Lactate formation and utilization occurs in different cell types even under fully aerobic conditions, where lactate functions as an energy source, signaling molecule, and pH regulator. 3
- The enzyme maintains adequate ATP supply across tissues through isoenzyme switching under various metabolic circumstances 1
- LDH has multi-organellar locations beyond its predominant cytoplasmic presence 1
Structural and Regulatory Properties
LDH exists as five isoenzyme forms composed of two subunit types (M and H), each with distinct biochemical properties including different substrate affinities, inhibition constants, and electrophoretic mobility. 1
- These isoforms vary in isoelectric points, providing cellular, tissue, and organ specificity 1
- The enzyme can undergo allosteric regulation, with some forms displaying homotropic and heterotropic activation 4
- Post-translational modifications enable diversified metabolic roles 1
Clinical Significance as a Biomarker
When cells are damaged, LDH leaks into serum, making elevated serum LDH a nonspecific marker of tissue injury and cell death. 5, 1, 6
Diagnostic Applications:
- Distinguishing pleural effusions: Pleural fluid LDH >0.67 of upper limit of normal serum value identifies exudates with 98% sensitivity 5
- Cancer marker: Elevated LDH indicates high tumor burden in testicular germ cell tumors, melanoma, osteosarcoma, and hematologic malignancies 7, 8
- Prognostic indicator: LDH levels correlate with disease severity and mortality in multiple conditions including ARDS, COVID-19, and various cancers 3, 8
Tissue Distribution:
- Highest activities: heart, liver, skeletal muscle, kidney, and erythrocytes 6
- Lower activities: lung, smooth muscle, and brain 6
The widespread tissue distribution makes total LDH elevation nonspecific; clinical interpretation requires correlation with isoenzyme patterns and clinical context. 6, 8