Component

Human mitochondrial alanine aminotransferase / GPT2

Human mitochondrial alanine aminotransferase / GPT2

8 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Recombinant human GPT2 catalyzed alanine transamination, confirming a second human alanine aminotransferase distinct from GPT.

    Human mitochondrial alanine aminotransferase / GPT2 → L-Alanine source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human GPT2 expressed in E. coli
    limitations
    Functional-expression evidence; this study did not quantify B6-deficiency sensitivity.
    nutrient_topic
    Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
    organism
    Homo sapiens
    plain_language
    Human alanine metabolism has a separately encoded second enzyme.
    primary_references
    [b6-gpt2-2002] cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase (2002). https://pubmed.ncbi.nlm.nih.gov/11863375/ DOI: 10.1006/geno.2002.6722
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 776–785

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GPT2 expressed in E. coli · source_derived_draft · unverified_draft

    ### b6-met-gpt2-reaction Recombinant human GPT2 catalyzed alanine transamination, confirming a second human alanine aminotransferase distinct from GPT. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human alanine metabolism has a separately encoded second enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human GPT2 expressed in E. coli limitations: Functional-expression evidence; this study did not quantify B6-deficiency sensitivity. [b6-gpt2-2002] cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase (2002). https://pubmed.ncbi.nlm.nih.gov/11863375/ DOI: 10.1006/geno.2002.6722
    Complete structured claim and evidence

What acts on it

  1. Human hepatic GPT2 mRNA decreased after bariatric surgery in the study samples.

    Bariatric surgery-associated weight loss → Human mitochondrial alanine aminotransferase / GPT2 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human liver expression measurements before/after surgical weight loss.
    limitations
    Multiple metabolic changes accompany surgery; this is not an alanine intervention. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    A human association complements the mouse mechanism but does not establish the same cause.
    primary_references
    Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 240–246

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver expression measurements before/after surgical weight loss. · source_derived_draft · unverified_draft

    ## alanine-human-bariatric-expression A human association complements the mouse mechanism but does not establish the same cause. Human hepatic GPT2 mRNA decreased after bariatric surgery in the study samples. Model: Human liver expression measurements before/after surgical weight loss. Limitations: Multiple metabolic changes accompany surgery; this is not an alanine intervention. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
    Complete structured claim and evidence

  2. The human GPT2 p.Arg404* and p.Pro272Leu variants were biochemically loss-of-function in kindreds with developmental disability, postnatal microcephaly and frequent progressive motor symptoms.

    Human recessive GPT2 loss-of-function variants → Human mitochondrial alanine aminotransferase / GPT2 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human families plus biochemical variant assays; accompanying mouse metabolic experiments.
    limitations
    Clinical association and enzyme loss do not establish that low dietary alanine caused the phenotype or that supplementation treats it.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    A genetic defect in alanine-related metabolism can affect brain growth and movement.
    primary_references
    Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27601654/ · DOI 10.1073/pnas.1609221113
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 296–302

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human families plus biochemical variant assays; accompanying mouse metabolic experiments. · source_derived_draft · unverified_draft

    ## alanine-human-gpt2-variants A genetic defect in alanine-related metabolism can affect brain growth and movement. The human GPT2 p.Arg404* and p.Pro272Leu variants were biochemically loss-of-function in kindreds with developmental disability, postnatal microcephaly and frequent progressive motor symptoms. Model: Human families plus biochemical variant assays; accompanying mouse metabolic experiments. Limitations: Clinical association and enzyme loss do not establish that low dietary alanine caused the phenotype or that supplementation treats it. Evidence access: Primary abstract Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27601654/ · DOI 10.1073/pnas.1609221113
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Combined inhibition of alanine synthesis and uptake suppressed fibrogenic responses in human fibroblasts and precision-cut lung slices.

    Combined alanine synthesis and uptake blockade → Human lung myofibroblast differentiation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cells and ex vivo lung tissue; metabolic perturbations.
    limitations
    Preclinical work, not an established human antifibrotic therapy. The final paper and its preprint are one study lineage.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    Blocking both supply routes had a stronger mechanistic rationale than assuming only one route mattered.
    primary_references
    TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 528–534

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cells and ex vivo lung tissue; metabolic perturbations. · source_derived_draft · unverified_draft

    ## alanine-fibroblast-dual-block Blocking both supply routes had a stronger mechanistic rationale than assuming only one route mattered. Combined inhibition of alanine synthesis and uptake suppressed fibrogenic responses in human fibroblasts and precision-cut lung slices. Model: Human cells and ex vivo lung tissue; metabolic perturbations. Limitations: Preclinical work, not an established human antifibrotic therapy. The final paper and its preprint are one study lineage. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
    Complete structured claim and evidence

  2. GPT2 inhibition lowered alanine and reduced TGF-beta-induced alpha-SMA and COL1A1 expression; 2 mM exogenous alanine rescued these readouts.

    L-Alanine → Human lung myofibroblast differentiation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human lung fibroblast perturbation and add-back experiments.
    limitations
    Marker rescue in cells is not a clinical fibrosis outcome.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    Alanine add-back bypassed part of the inhibited synthesis pathway.
    primary_references
    TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 512–518

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung fibroblast perturbation and add-back experiments. · source_derived_draft · unverified_draft

    ## alanine-fibroblast-gpt2-rescue Alanine add-back bypassed part of the inhibited synthesis pathway. GPT2 inhibition lowered alanine and reduced TGF-beta-induced alpha-SMA and COL1A1 expression; 2 mM exogenous alanine rescued these readouts. Model: Human lung fibroblast perturbation and add-back experiments. Limitations: Marker rescue in cells is not a clinical fibrosis outcome. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
    Complete structured claim and evidence

  3. TGF-beta increased alanine synthesis in normal and IPF human lung fibroblasts, with GPT2 as the principal examined synthesis enzyme regulated by the glutamine/glutamate/2-oxoglutarate axis.

    Transforming growth factor beta 1 → Alanine availability in human lung fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human lung fibroblast cultures; TGF-beta 2 ng/mL and metabolic perturbations.
    limitations
    Medium composition matters; this is not proof that alanine intake causes lung fibrosis.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    A differentiation signal coordinates alanine production with other amino-acid metabolism.
    primary_references
    TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 496–502

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung fibroblast cultures; TGF-beta 2 ng/mL and metabolic perturbations. · source_derived_draft · unverified_draft

    ## alanine-fibroblast-synthesis A differentiation signal coordinates alanine production with other amino-acid metabolism. TGF-beta increased alanine synthesis in normal and IPF human lung fibroblasts, with GPT2 as the principal examined synthesis enzyme regulated by the glutamine/glutamate/2-oxoglutarate axis. Model: Human lung fibroblast cultures; TGF-beta 2 ng/mL and metabolic perturbations. Limitations: Medium composition matters; this is not proof that alanine intake causes lung fibrosis. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
    Complete structured claim and evidence

  4. UK-5099 inhibition of mitochondrial pyruvate transport reduced alanine synthesis/secretion and increased uptake of extracellular alanine; alanine supplementation restored intracellular levels.

    Mitochondrial pyruvate carrier inhibition in human PDAC → L-Alanine source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human PDAC cultures; MPC inhibitor and isotope tracing.
    limitations
    A pharmacological perturbation is not evidence that usual alanine intake bypasses every mitochondrial defect.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    When pyruvate cannot reach the synthesis compartment, imported alanine becomes more important.
    primary_references
    Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 200–206

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures; MPC inhibitor and isotope tracing. · source_derived_draft · unverified_draft

    ## alanine-pdac-mpc When pyruvate cannot reach the synthesis compartment, imported alanine becomes more important. UK-5099 inhibition of mitochondrial pyruvate transport reduced alanine synthesis/secretion and increased uptake of extracellular alanine; alanine supplementation restored intracellular levels. Model: Human PDAC cultures; MPC inhibitor and isotope tracing. Limitations: A pharmacological perturbation is not evidence that usual alanine intake bypasses every mitochondrial defect. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
    Complete structured claim and evidence

  5. SLC38A2-deficient PDAC cells increased de novo alanine synthesis and passive efflux, diverting mitochondrial pyruvate and amino-nitrogen sources toward alanine production.

    SLC38A2 loss in human PDAC cells → De novo alanine synthesis in human PDAC cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human PDAC flux and compartmental metabolism experiments.
    limitations
    Reported metabolic crisis is not a universal consequence of reduced dietary alanine.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    Losing uptake can force a cell to spend other nutrients making the missing amino acid.
    primary_references
    Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 192–198

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC flux and compartmental metabolism experiments. · source_derived_draft · unverified_draft

    ## alanine-pdac-snat2-carbon-cost Losing uptake can force a cell to spend other nutrients making the missing amino acid. SLC38A2-deficient PDAC cells increased de novo alanine synthesis and passive efflux, diverting mitochondrial pyruvate and amino-nitrogen sources toward alanine production. Model: Human PDAC flux and compartmental metabolism experiments. Limitations: Reported metabolic crisis is not a universal consequence of reduced dietary alanine. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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