Fumarate hydratase Recombinant Rabbit mAb, PBS Only (SDT-2394-36)

Fumarate hydratase (FH) is a mitochondrial and cytoplasmic metabolic enzyme encoded by the FH gene that catalyzes the reversible stereospecific hydration of fumarate to L-malate within the tricarboxylic acid cycle, a reaction essential for NADH production and cellular energy homeostasis; beyond this canonical metabolic role, FH acts as a tumor suppressor because loss-of-function mutations lead to intracellular accumulation of the oncometabolite fumarate, which inhibits α-ketoglutarate-dependent dioxygenases (including HIF prolyl-hydroxylases and histone demethylases), thereby stabilizing HIF-1α, driving pseudohypoxic gene expression, succinating KEAP1 to activate Nrf2 antioxidant signaling, and ultimately promoting hereditary leiomyomatosis and renal cell carcinoma, while complete FH deficiency causes the severe neurometabolic disorder fumaric aciduria characterized by encephalopathy, developmental delay, and elevated fumarate levels, and the enzyme also moonlights in DNA repair by translocating to double-strand breaks where locally generated fumarate enhances non-homologous end-joining through inhibition of KDM2B and increased H3K36 dimethylation.