Aspartate aminotransferase (AST) (AST)

Aspartate aminotransferase (AST), historically known as glutamic-oxaloacetic transaminase (GOT), is a vital pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the reversible transfer of an amino group between aspartate and glutamate [6, 13]. It exists in two primary isoforms: the cytosolic GOT1 and the mitochondrial GOT2, which together facilitate the malate-aspartate shuttle and maintain cellular redox balance [1, 10]. While traditionally utilized as a clinical biomarker for liver and cardiac damage, AST has emerged as a significant therapeutic target in oncology [2, 14]. Many cancer cells, particularly those with KRAS mutations, rely on GOT1 to maintain the aspartate pools necessary for nucleotide synthesis and to manage oxidative stress [5, 10]. Consequently, inhibiting GOT1 can disrupt cancer cell metabolism and sensitize tumors to other therapies [1, 5]. However, the development of selective inhibitors remains a challenge due to the enzyme's essential role in systemic amino acid metabolism and the potential for off-target effects on other transaminases [1, 9].

Other names

Glutamic-oxaloacetic transaminaseGlutamate oxaloacetate transaminaseSerum glutamic-oxaloacetic transaminaseSGOTAspartate transaminaseASATAspATAAT

Competitive inhibition of the active site or irreversible inhibition of the pyridoxal phosphate cofactor, disrupting the transamination of aspartate and alpha-ketoglutarate [1, 9].