GOT2 is the mitochondrial matrix aspartate aminotransferase, a homodimeric pyridoxal 5'-phosphate-dependent enzyme. It reversibly interconverts L-aspartate and 2-oxoglutarate with oxaloacetate and L-glutamate, providing the mitochondrial transamination step of the malate-aspartate shuttle and linking amino-acid and carbon metabolism. The shuttle transfers reducing equivalents through coupled metabolic and transport reactions; GOT2 itself neither transports NADH nor catalyzes its oxidation. Biallelic loss of function causes a developmental and epileptic encephalopathy with disrupted cellular redox metabolism. Additional activities include kynurenine transamination and participation in hydroxyproline degradation. A plasma-membrane-associated pool, also called FABPpm, is linked to long-chain fatty-acid uptake in particular cellular contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: The inherited mitochondrial assignment agrees with curated GOT2 matrix localization and target mitochondrial observations. The legacy seed does not retain the ancestral PTN, so its precise node placement has not been reconstructed; a missing identifier is not evidence against the independently supported organelle claim. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0006533 L-aspartate catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: The enzyme directly executes this substrate/product interconversion. Reason: The measured reversible reaction directly produces or consumes the named amino acid or ketoacid. Its net direction depends on compartment and metabolic state; synthesis and degradation annotations are therefore compatible. The term is supported by chemistry, not merely by altered metabolite abundance following perturbation. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the general catalytic/transaminase label to the supported specific reactions. Reason: The broad parent chemistry is true. Preserve the established aspartate activity and the separately retained secondary substrate activities, rather than treating genericity as biological over-annotation. Their non-core or ortholog-supported scope remains explained in the corresponding specific rows. Proposed replacements: L-aspartate:2-oxoglutarate transaminase activity L-kynurenine:2-oxoglutarate transaminase activity Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0005759 mitochondrial matrix | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the established catalytic compartment of the mature enzyme. Reason: Independent human localization/biochemical evidence and the curated reaction records consistently support this compartment. Repeated reaction records are not counted as independent localization experiments. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Retain the plasma-membrane-associated fatty-acid-uptake/ethanol context. Reason: Human HepG2 experiments in PMID:9537447 relate ethanol exposure to increased membrane mAspAT/FABPpm and fatty-acid uptake, while mitochondrial protein levels remain unchanged. This supports the established contextual moonlighting role and localization, but not an assertion that all matrix GOT2 performs fatty-acid transport or that GOT2 alone is a transmembrane pore. Supporting Evidence: PMID:9537447 fatty acid uptake Vmax increased in parallel with plasma membrane expression of mAspAT |
| GO:0006520 amino acid metabolic process | IEA GO_REF:0000002 | MODIFY | Summary: Refine generic amino-acid metabolism to the directly executed aspartate/glutamate reactions. Reason: The reversible transfer directly produces and consumes amino acids. The narrower aspartate and glutamate processes capture the work of the enzyme without suggesting a generic role in every amino-acid pathway. Proposed replacements: aspartate metabolic process glutamate metabolic process Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0006533 L-aspartate catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: The enzyme directly executes this substrate/product interconversion. Reason: The measured reversible reaction directly produces or consumes the named amino acid or ketoacid. Its net direction depends on compartment and metabolic state; synthesis and degradation annotations are therefore compatible. The term is supported by chemistry, not merely by altered metabolite abundance following perturbation. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0008483 transaminase activity | IEA GO_REF:0000002 | MODIFY | Summary: Refine the general catalytic/transaminase label to the supported specific reactions. Reason: The broad parent chemistry is true. Preserve the established aspartate activity and the separately retained secondary substrate activities, rather than treating genericity as biological over-annotation. Their non-core or ortholog-supported scope remains explained in the corresponding specific rows. Proposed replacements: L-aspartate:2-oxoglutarate transaminase activity L-kynurenine:2-oxoglutarate transaminase activity Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0016212 L-kynurenine:2-oxoglutarate transaminase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Retain secondary kynurenine aminotransferase activity with its homolog-inference scope. Reason: The curated human reaction is inferred from pig mitochondrial AspAT P00507. It is a recognized alternative substrate reaction of GOT2/KAT4, but the core human disease/AST assays do not themselves measure kynurenine kinetics or quantify its contribution in every tissue. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-kynurenine + 2-oxoglutarate = kynurenate + L-glutamate + |
| GO:0030170 pyridoxal phosphate binding | IEA GO_REF:0000002 | ACCEPT | Summary: PLP is the catalytic cofactor of this aminotransferase. Reason: The curated cofactor and PLP-linked active-site feature support the cofactor mechanism. It is integrated into the transaminase core rather than described as a separate physiological role. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Name=pyridoxal 5'-phosphate |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | EXP PMID:26902786 Recombinant expression, purification and crystallographic st... | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | EXP PMID:31422819 Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate... | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0043490 malate-aspartate shuttle | IMP PMID:37647199 The malate-aspartate shuttle is important for de novo serine... | ACCEPT | Summary: GOT supplies one catalytic transamination step of the malate-aspartate shuttle. Reason: The original PMID:37647199 perturbs a panel of MAS components in human HEK293 cells. Its abstract does not enumerate every genotype, but the established compartment-specific chemistry and curated pathway support the assertion. The shuttle transfers reducing equivalents through several enzymes and carriers; GOT itself is not an NADH transporter or dehydrogenase. Impaired serine synthesis is a redox consequence, not direct serine synthesis by GOT. Supporting Evidence: PMID:37647199 We genetically disrupted each MAS component to generate a panel of MAS-deficient HEK293 cell lines file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: PMID:34800366 uses complementary subtractive proteomics, spatial profiling and importomics to define the human mitochondrial proteome. The original GOT2 organelle assignment agrees with independently curated matrix localization; this row does not assert that the proteomics measurement alone resolved matrix topology. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-6784393 | ACCEPT | Summary: Retain the established catalytic compartment of the mature enzyme. Reason: Independent human localization/biochemical evidence and the curated reaction records consistently support this compartment. Repeated reaction records are not counted as independent localization experiments. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-70596 | ACCEPT | Summary: Retain the established catalytic compartment of the mature enzyme. Reason: Independent human localization/biochemical evidence and the curated reaction records consistently support this compartment. Repeated reaction records are not counted as independent localization experiments. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0005759 mitochondrial matrix | TAS Reactome:R-HSA-70613 | ACCEPT | Summary: Retain the established catalytic compartment of the mature enzyme. Reason: Independent human localization/biochemical evidence and the curated reaction records consistently support this compartment. Repeated reaction records are not counted as independent localization experiments. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Retain the curated contextual proteomic localization. Reason: The cited human proteomic study reports the compartment preparation underlying this assertion. The target-specific peptide table was not reconstructed for every screen; accept the curator attribution conservatively, without inferring a dedicated vesicle/nuclear function or dismissing it as contamination merely because the enzyme usually acts elsewhere. Supporting Evidence: |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | KEEP AS NON CORE | Summary: Retain the experimental RNA-association finding without inventing an RNA-regulatory mechanism. Reason: PMID:22681889 uses photoreactive nucleotide-enhanced UV crosslinking, oligo(dT) purification and quantitative proteomics in human cells. A mitochondrial metabolic enzyme can also bind RNA; its usual catalytic role is not evidence against this experimental assertion. Retain the curator-defined detection as non-core, with target-peptide and RNA-specificity details not independently reconstructed from the abstract. Supporting Evidence: PMID:22681889 photoreactive nucleotide-enhanced UV crosslinking and oligo(dT) purification approach |
| GO:0005739 mitochondrion | HDA PMID:20833797 Phosphoproteome analysis of functional mitochondria isolated... | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: PMID:20833797 studies functional mitochondria isolated from human muscle biopsies. Retain the original GOT2 mitochondrial proteomics assignment, consistent with independently curated matrix localization, without upgrading the assay to a matrix-specific localization experiment. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: Retain the curated contextual proteomic localization. Reason: The cited human proteomic study reports the compartment preparation underlying this assertion. The target-specific peptide table was not reconstructed for every screen; accept the curator attribution conservatively, without inferring a dedicated vesicle/nuclear function or dismissing it as contamination merely because the enzyme usually acts elsewhere. Supporting Evidence: |
| GO:0019470 trans-4-hydroxy-L-proline catabolic process | TAS PMID:21998747 Structural and biochemical studies of human 4-hydroxy-2-oxog... | KEEP AS NON CORE | Summary: GOT2 performs the transamination step of hydroxyproline degradation. Reason: The original HOGA1 paper PMID:21998747 places AspAT in the mitochondrial pathway, and Reactome specifically models GOT2 conversion of hydroxyglutamate to the ketoacid HOG. This supports direct pathway participation as a secondary substrate route; the HOGA1 paper is not newly presented as a purified human GOT2 substrate-kinetics experiment. Reactome explicitly identifies the human reaction as an inference from the rat homolog, not a direct human enzyme assay. Supporting Evidence: Reactome:R-HSA-6784393 GOT2 dimer transaminates 4-OH-L-glutamate (4-OH-L-Glu) and 2-oxoglutarate (2OG) to form 4-hydroxy-2-oxoglutarate (HOG) and L-Glu. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | ISS GO_REF:0000024 | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0005739 mitochondrion | ISS GO_REF:0000024 | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: The similarity-based mitochondrial assignment agrees with target mitochondrial observations and curated GOT2 matrix localization. The source basis supports the organelle claim; no newly established ortholog-specific topology assay or phylogenetic node reconstruction is implied. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix |
| GO:0006103 2-oxoglutarate metabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: The enzyme directly executes this substrate/product interconversion. Reason: The measured reversible reaction directly produces or consumes the named amino acid or ketoacid. Its net direction depends on compartment and metabolic state; synthesis and degradation annotations are therefore compatible. The term is supported by chemistry, not merely by altered metabolite abundance following perturbation. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0006531 aspartate metabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Refine the general amino-acid process to both supported directions of the reaction. Reason: The enzyme directly makes and consumes this amino acid in its reversible transamination. Retain both directional descendants, rather than implying only one fixed flux direction. Proposed replacements: L-aspartate biosynthetic process L-aspartate catabolic process Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0006536 glutamate metabolic process | ISS GO_REF:0000024 | MODIFY | Summary: Refine the general amino-acid process to both supported directions of the reaction. Reason: The enzyme directly makes and consumes this amino acid in its reversible transamination. Retain both directional descendants, rather than implying only one fixed flux direction. Proposed replacements: L-glutamate biosynthetic process L-glutamate catabolic process Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:2182221 New automated measurement of mitochondrial aspartate aminotr... | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. PMID:2182221 selectively inactivates cytosolic AST and PLP-activates mitochondrial AST in human serum; this is not a new physiological localization experiment. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:2567216 Serum mitochondrial aspartate aminotransferase activity: not... | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0004069 L-aspartate:2-oxoglutarate transaminase activity | IDA PMID:2731362 Effects of therapeutic coronary reperfusion on aspartate ami... | ACCEPT | Summary: The core aspartate aminotransferase reaction is directly supported for this human enzyme. Reason: The defining human aspartate/2-oxoglutarate reaction is established independently by biochemical characterization and disease-variant studies. Retain all evidence-coded assertions consistently; PAINT describes an ancestral function, not a donor-count vote. Diagnostic papers can assay both isoenzymes even when their titles emphasize only one. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; PMID:31422819 GOT2 enzyme activity was deficient in fibroblasts with bi-allelic mutations. |
| GO:0006533 L-aspartate catabolic process | IDA PMID:2567216 Serum mitochondrial aspartate aminotransferase activity: not... | ACCEPT | Summary: The enzyme directly executes this substrate/product interconversion. Reason: The measured reversible reaction directly produces or consumes the named amino acid or ketoacid. Its net direction depends on compartment and metabolic state; synthesis and degradation annotations are therefore compatible. The term is supported by chemistry, not merely by altered metabolite abundance following perturbation. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Reaction=L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate; |
| GO:0005739 mitochondrion | IDA PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | ACCEPT | Summary: Retain the supported mitochondrial localization alongside the existing matrix annotation. Reason: PMID:9537447 reports that mitochondrial mAspAT levels in HepG2 cells were unchanged during ethanol exposure while plasma-membrane mAspAT increased. This directly supports a mitochondrial pool alongside the separately retained plasma-membrane pool, without establishing that every cellular GOT2 molecule is mitochondrial. Retain the informative mitochondrion assertion under the root-organelle policy; existing mitochondrial matrix annotations are separate and are not substituted for this row. Supporting Evidence: file:human/GOT2/GOT2-uniprot.txt Mitochondrion matrix PMID:9537447 Plasma membrane mAspAT content also correlated with mAspAT mRNA (r = .96) and mitochondrial levels were unchanged. |
| GO:0005886 plasma membrane | IDA PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | KEEP AS NON CORE | Summary: Retain the plasma-membrane-associated fatty-acid-uptake/ethanol context. Reason: Human HepG2 experiments in PMID:9537447 relate ethanol exposure to increased membrane mAspAT/FABPpm and fatty-acid uptake, while mitochondrial protein levels remain unchanged. This supports the established contextual moonlighting role and localization, but not an assertion that all matrix GOT2 performs fatty-acid transport or that GOT2 alone is a transmembrane pore. Supporting Evidence: PMID:9537447 fatty acid uptake Vmax increased in parallel with plasma membrane expression of mAspAT |
| GO:0015908 fatty acid transport | IEP PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | KEEP AS NON CORE | Summary: Retain the plasma-membrane-associated fatty-acid-uptake/ethanol context. Reason: Human HepG2 experiments in PMID:9537447 relate ethanol exposure to increased membrane mAspAT/FABPpm and fatty-acid uptake, while mitochondrial protein levels remain unchanged. This supports the established contextual moonlighting role and localization, but not an assertion that all matrix GOT2 performs fatty-acid transport or that GOT2 alone is a transmembrane pore. Supporting Evidence: PMID:9537447 fatty acid uptake Vmax increased in parallel with plasma membrane expression of mAspAT |
| GO:0045471 response to ethanol | IDA PMID:9537447 Ethanol up-regulates fatty acid uptake and plasma membrane e... | KEEP AS NON CORE | Summary: Retain the plasma-membrane-associated fatty-acid-uptake/ethanol context. Reason: Human HepG2 experiments in PMID:9537447 relate ethanol exposure to increased membrane mAspAT/FABPpm and fatty-acid uptake, while mitochondrial protein levels remain unchanged. This supports the established contextual moonlighting role and localization, but not an assertion that all matrix GOT2 performs fatty-acid transport or that GOT2 alone is a transmembrane pore. Supporting Evidence: PMID:9537447 fatty acid uptake Vmax increased in parallel with plasma membrane expression of mAspAT |
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Download this section (compressed HTML)Q: How is GOT2 partitioned between its mitochondrial-matrix transaminase pool and the plasma-membrane FABPpm pool, and what signals (beyond ethanol) control the translocation?
Q: What is the quantitative contribution of GOT2's kynurenine aminotransferase (KAT4) activity to kynurenic acid production relative to the other human KATs in different tissues?
Experiment: Isoform-/pool-resolved metabolic-flux analysis (13C tracing) in GOT2-knockout versus wild-type human cells to quantify its contribution to the malate-aspartate shuttle, NAD(H) redox balance and de novo serine biosynthesis.
Experiment: Structure-guided separation-of-function mutants that disrupt the long-chain-fatty-acid binding site without affecting transaminase activity, to test whether the FABPpm fatty-acid-uptake role is genuinely independent of catalysis.
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