L-lactate dehydrogenase A chain

L-lactate dehydrogenase A chain (LDHA, also known as LDH-A) is a metabolic enzyme that catalyzes the reversible interconversion of pyruvate and lactate coupled with NADH and NAD+ cycling (UniProt: P00338). This 36.7 kDa protein plays a central role in anaerobic glycolysis and lactate metabolism. Mutations in LDHA cause glycogen storage disease 11, a metabolic disorder characterized by exertional myoglobinuria and muscle fatigue (UniProt: P00338).

LDHA is widely expressed across tissues where energy metabolism is active, particularly in muscle and brain. The protein is fundamental to cellular energy production under both aerobic and anaerobic conditions.

In Alzheimer's disease, LDHA is downregulated in post-mortem human brain tissue compared to age-matched controls (Chaparral AD proteomics). Analysis of subcellular fractions by TMT-labeled quantitative proteomics revealed a mean log2 fold-change of −0.54 across detected fractions, indicating reduced abundance. This downregulation may reflect altered metabolic capacity or energy production in AD-affected brain tissue, though the functional consequences remain to be determined.