Target intelligence / Profile preview

Aspartate aminotransferase, mitochondrial (GOT2)

Target
GOT2
Molecular classification
Enzyme, Aminotransferase, Pyridoxal phosphate-dependent enzyme, Fatty acid-binding protein
01

Overview

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].

Other names
Glutamic-oxaloacetic transaminase 2GOT2Aspartate transaminase 2mAspATKYAT4KAT4KATIVFatty acid-binding protein, plasma membrane (FABPpm)Plasma membrane-associated fatty acid-binding proteinKynurenine aminotransferase IVKynurenine--oxoglutarate transaminase IVTransaminase ADEE82
02

Mechanism of action

Inhibitors block transamination of aspartate and the malate-aspartate shuttle, which disrupts cellular redox balance and aspartate supply necessary for cell proliferation[1][5].

03

Biological functions

Amino acid metabolismTricarboxylic acid (Krebs) cycleMalate-aspartate shuttleNAD+/NADH redox balanceFatty acid uptake and metabolismKynurenine pathway (tryptophan metabolism)
04

Disease associations

Cancer (notably implicated in tumor proliferation)Neurodegenerative disease (through kynurenine pathway neurotoxicity)Developmental and epileptic encephalopathyCardiovascular disease (role in cardiac energy metabolism)
05

Safety considerations

Inhibiting mitochondrial aspartate aminotransferase may impair normal cellular metabolism, especially in heart, muscle, and liver, creating possible risks of metabolic and energetic dysfunction[1][2].Potential neurotoxicity by altering kynurenic acid levels in the brain[1].
06

Interacting drugs

No specific approved small-molecule drugs directly targeting GOT2 are currently listed in major databases or literature[5]. Some experimental inhibitors and research compounds (e.g., aminooxyacetic acid) are studied for inhibition, but not approved clinically.
07

Biomarkers

Serum aspartate aminotransferase (AST, includes both cytosolic and mitochondrial forms) as a liver dysfunction or damage biomarker[4].Mitochondrial AST levels (for developmental and epileptic encephalopathy prognosis or diagnosis)[5].

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