GOT2 (Glutamic-Oxaloacetic Transaminase 2), also known as mitochondrial aspartate aminotransferase (mAST), is a critical mitochondrial enzyme that catalyzes the reversible transamination between aspartate and alpha-ketoglutarate to form glutamate and oxaloacetate. This reaction is central to multiple metabolic pathways including the malate-aspartate shuttle, amino acid metabolism, and the urea cycle. In neurons, GOT2 plays an essential role in maintaining mitochondrial function and protecting against oxidative stress—two processes fundamental to Alzheimer's disease and Parkinson's disease pathogenesis.
| GOT2 Gene | |
|---|---|
| Gene Symbol | GOT2 |
| Full Name | Glutamic-Oxaloacetic Transaminase 2 |
| Chromosomal Location | 16q21 |
| NCBI Gene ID | [2805](https://www.ncbi.nlm.nih.gov/gene/2805) |
| OMIM | [138150](https://www.omim.org/entry/138150) |
| Ensembl ID | ENSG00000125107 |
| UniProt ID | [P07148](https://www.uniprot.org/uniprot/P07148) |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Stroke, Metabolic Disorders |
GOT2 is a pyridoxal phosphate (PLP)-dependent enzyme localized to the mitochondrial matrix. It catalyzes:
Aspartate + α-Ketoglutarate ⇌ Oxaloacetate + Glutamate
This reversible reaction allows the interconversion of:
| Pathway | Role of GOT2 |
|---|---|
| Malate-Aspartate Shuttle | Primary transporter of reducing equivalents (NADH) from cytosol to mitochondria |
| TCA Cycle | Generates oxaloacetate for citrate synthesis |
| Urea Cycle | Produces aspartate for argininosuccinate synthesis |
| Amino Acid Metabolism | Transamination of multiple amino acids |
The malate-aspartate shuttle is critical for:
GOT2 dysfunction may contribute to Alzheimer's disease pathogenesis through several mechanisms:
In Parkinson's disease, GOT2 is particularly important for:
The aging brain shows progressive decline in GOT2 function[3][4]:
Several GOT2 polymorphisms have been associated with neurodegenerative disease susceptibility[5][6]:
GOT2 is a homodimer with:
| Property | Value |
|---|---|
| Molecular weight | ~90 kDa (dimer) |
| Isoelectric point | ~6.5 |
| Optimal pH | 7.5-8.5 |
| Substrate affinity (Asp) | Km ~0.5 mM |
| Substrate affinity (α-KG) | Km ~0.2 mM |
GOT2 has potential as a biomarker for neurodegenerative diseases[7]:
Several therapeutic approaches target GOT2-related pathways[8]:
GOT2 plays a critical role in metabolic coupling between astrocytes and neurons[9]:
Recent research has revealed several key insights:
GOT2 is ubiquitously expressed with highest levels in:
| Tissue | Expression Level | Significance |
|---|---|---|
| Brain | High | Neuronal energy metabolism |
| Heart | Very high | Continuous energy demand |
| Liver | High | Urea cycle, amino acid metabolism |
| Kidney | High | Amino acid homeostasis |
| Skeletal muscle | Moderate | Energy metabolism |
Lee S, et al. Mitochondrial aspartate aminotransferase in dopaminergic neurons. Journal of Neurochemistry. 2022. ↩︎
Birk J, et al. Mitochondrial metabolism in Parkinson's disease: Got2 and the malate-aspartate shuttle. Journal of Neuroscience. 2019. ↩︎
Taylor J, et al. Proteomic analysis of GOT2 in aging brains. Neurobiology of Aging. 2021. ↩︎
Cheng X, et al. Malate-aspartate shuttle dysfunction in aging brain. Aging Cell. 2024. ↩︎
Patel P, et al. GOT2 polymorphisms and susceptibility to neurodegenerative diseases. Journal of Molecular Neuroscience. 2023. ↩︎
Nguyen T, et al. GOT2 mutations and early-onset neurodegenerative disease. Human Molecular Genetics. 2023. ↩︎
Kim Y, et al. GOT2 as a prognostic biomarker in gliomas and its metabolic role. Oncogene. 2020. ↩︎
Song Q, et al. Targeting mitochondrial metabolic dysfunction in neurodegeneration. Nature Reviews Neurology. 2023. ↩︎
Martin A, et al. Metabolic coupling between astrocytes and neurons: The role of GOT2. Glia. 2023. ↩︎
Wang L, et al. GOT2 and the malate-aspartate shuttle in amyloid-beta toxicity. Cellular and Molecular Neurobiology. 2024. ↩︎