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Lactate dehydrogenase A (LDHA) is an enzyme encoded by the LDHA gene in humans and is a subunit of the lactate dehydrogenase (LDH) enzyme, which exists as a tetramer of either LDHA (M) or LDHB (H) subunits, or a mix of both. The enzyme catalyzes the interconversion of pyruvate and lactate with concomitant conversion of NADH to NAD⁺, a critical step in anaerobic glycolysis. LDHA is highly expressed in skeletal muscle and many tumors, where it supports energy production in oxygen-limited conditions. Elevated LDHA is associated with cancer progression and poor prognosis, making it a potential therapeutic target. Mutations in the LDHA gene can cause lactate dehydrogenase-A deficiency, leading to exercise intolerance, muscle pain, and rhabdomyolysis. Several inhibitors of LDHA have been identified, primarily for experimental and potential therapeutic use in cancer.
Inhibition of LDHA enzymatic activity disrupts anaerobic glycolysis, reducing ATP production in cancer cells and increasing reactive oxygen species (ROS), leading to cancer cell death or reduced proliferation Competitive inhibition at the active site (e.g., oxamate)
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