Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and NADH to lactate and NAD+. When the oxygen supply is too low for mitochondrial ATP production, this reaction recycles NADH generated in glycolysis to NAD+, which reenters glycolysis. The major form of LDH found in muscle cells is the A (LDHA) isozyme. The LDHA promoter contains HIF-1α binding sites (1). LDHA expression is induced under hypoxic conditions (2). During intensive and prolonged muscle exercise, lactate accumulates in muscle cells when the supply of oxygen does not meet demand. When oxygen levels return to normal, LDH converts lactate to pyruvate to generate ATP in the mitochondrial electron transport chain.
