Aspartate aminotransferase, cytoplasmic

Aspartate aminotransferase, cytoplasmic (GOT1) is a pyridoxal phosphate-dependent enzyme that catalyzes the reversible transamination of aspartate and α-ketoglutarate to form oxaloacetate and glutamate (UniProt: P17174). Beyond its classical hepatic and adipose roles in glucose and lipid metabolism, GOT1 functions as a critical regulator of glutamate homeostasis in the central nervous system, acting as a glutamate scavenger for neuroprotection. The enzyme also participates in hydrogen sulfide synthesis via mercaptopyruvate metabolism, supporting synaptic modulation and cellular defense mechanisms in the brain.

GOT1 is broadly expressed across tissues and is positioned at the intersection of amino acid, energy, and redox metabolism in neurons and glia (UniProt: P17174). Its role in maintaining glutamate levels and generating neuroprotective metabolites highlights its relevance to neuronal function and resilience.

GOT1 is down-regulated in Alzheimer's disease brain tissue compared to age-matched controls in post-mortem proteomics analysis (Chaparral AD proteomics; mean log2FC = −0.58 across two subcellular fractions). The reduction in this glutamate-scavenging and neuroprotective enzyme may contribute to excitotoxic stress and impaired metabolic support during neurodegeneration in AD.