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Aspartate aminotransferase, mitochondrial (GOT2), is a pyridoxal phosphate-dependent enzyme localized to the mitochondrial matrix, where it catalyzes the reversible transamination between aspartate and α-ketoglutarate to produce oxaloacetate and glutamate[1][4][5]. It is a critical component of the malate-aspartate shuttle, facilitating transfer of reducing equivalents (NADH) from cytosol to mitochondria, which is essential for cellular energy metabolism. GOT2 also participates in the synthesis of kynurenic acid from kynurenine in the brain, linking it to neurological processes and potentially neurodegenerative disorders. Beyond its central role in metabolism, GOT2 has been associated with tumor proliferation (notably in pancreatic and breast cancer), cardiac energetics, and rare genetic encephalopathies. As a plasma membrane-associated fatty acid-binding protein (FABPpm), GOT2 also contributes to long-chain fatty acid uptake in metabolically active tissues[3]. Its functional importance in diverse tissues and pathways makes it a candidate for therapeutic targeting, notably in cancer, but also marks it as a node of significant physiological and safety relevance[1][2][3][5].
Inhibitors block transamination of aspartate and the malate-aspartate shuttle, which disrupts cellular redox balance and aspartate supply necessary for cell proliferation[1][5].
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