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Glutamic-oxaloacetic transaminase 1, soluble (GOT1), is a pyridoxal phosphate-dependent cytosolic enzyme that catalyzes the reversible transamination between aspartate and α-ketoglutarate to form oxaloacetate and glutamate, central to the malate-aspartate shuttle, amino acid metabolism, urea cycle, and TCA cycle. GOT1 plays a crucial role in supporting cell proliferation by synthesizing aspartate for nucleotide production, maintaining redox homeostasis via NADPH generation, and regulating glycolysis. It is highly conserved and related to its mitochondrial isozyme GOT2. GOT1's function is critical in tumor metabolism, and its inhibition has shown promise experimentally to sensitize cancer cells to certain chemotherapies, disrupt metabolic pathways, and modulate the immune response
Inhibition of transaminase function to disrupt aspartate synthesis, block nucleotide synthesis, and suppress cell proliferation Regulation of NADPH production impacts cellular redox balance, increasing reactive oxygen species (ROS) and sensitizing cancer cells to oxidative stress and chemotherapeutics Indirect influence on metabolic reprogramming, glycolysis, and immune cell fate through metabolite pools and epigenetic signaling
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