Target intelligence / Profile preview

Glutamic-oxaloacetic transaminase 1, soluble (GOT1)

Target
GOT1
Molecular classification
Enzyme (specifically, a pyridoxal phosphate-dependent transaminase; classified as aspartate aminotransferase, cytosolic)
01

Overview

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

Other names
GOT1ASTQTL1AST1CASPATGIG18cAspATcCAT
02

Mechanism of action

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

03

Biological functions

Amino acid metabolism (transamination)Urea cycleTricarboxylic acid (TCA) cycleSupply of aspartate for nucleotide synthesisRegulation of glycolysisMaintenance of cellular redox homeostasis (NADPH production and ROS balance)Regulation of immune cell function (especially CD8+ T cell expansion and effector differentiation)Epigenetic regulation (influencing cell fate through metabolite signaling)
04

Disease associations

Cancer (metabolic reprogramming of tumor cells and sensitivity to anti-cancer drugs)Metabolic syndromeDiabetes (regulation of β-cell function)Neuroprotection and brain excitotoxicityHepatic glucose synthesis and adipocyte metabolism
05

Safety considerations

GOT1 activity is essential for normal cellular metabolism (TCA cycle, amino acid metabolism, redox homeostasis)Inhibition may affect non-tumor cells, potentially leading to toxicity due to impaired metabolism, especially in tissues reliant on transamination and aspartate supplyCompensation by GOT2 or alternative pathways may limit therapeutic efficacy; metabolic flexibility in tumors may reduce the impact of GOT1 inhibition
06

Interacting drugs

aminooxyacetate (AOA)

3 more in the full profile.

07

Biomarkers

Serum aspartate aminotransferase (AST) levels: widely used clinical biomarker for liver function (though not specific to GOT1 alone)Expression of GOT1 in tumor tissues may be a biomarker for prognosis/aggressiveness in specific cancers

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