Component

Human methionine adenosyltransferase 2A / MAT2A

Human methionine adenosyltransferase 2A / MAT2A. Species, exposure and limitations are retained in each linked claim.

9 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. MAT2A depletion preferentially reduced growth and PRMT5 methylation activity in MTAP-deleted cells.

    Human methionine adenosyltransferase 2A / MAT2A → Human protein arginine methyltransferase 5 / PRMT5 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human cancer-cell genetic depletion experiments.
    limitations
    This genetic interaction is not proof of efficacy for methionine restriction or a particular drug in patients.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Loss of a recycling enzyme can make cells more sensitive to reduced donor synthesis.
    primary_references
    MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27068473/ · DOI 10.1016/j.celrep.2016.03.043
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 300–306

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell genetic depletion experiments. · source_derived_draft · unverified_draft

    ## methionine-mat2a-prmt5-vulnerability Loss of a recycling enzyme can make cells more sensitive to reduced donor synthesis. MAT2A depletion preferentially reduced growth and PRMT5 methylation activity in MTAP-deleted cells. Model: Human cancer-cell genetic depletion experiments. Limitations: This genetic interaction is not proof of efficacy for methionine restriction or a particular drug in patients. Evidence access: Primary abstract MTAP Deletions in Cancer Create Vulnerability to Targeting of the MAT2A/PRMT5/RIOK1 Axis. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27068473/ · DOI 10.1016/j.celrep.2016.03.043
    Complete structured claim and evidence

  2. Acute MAT2A depletion reduced mTORC1 responsiveness to methionine while largely preserving responsiveness to supplied SAM.

    Human methionine adenosyltransferase 2A / MAT2A → Methionine-to-mTORC1 coupling in human HEK293T 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 doxycycline-regulated MAT2A cells; starvation and repletion.
    limitations
    Cellular SAM addition is not evidence for equivalent oral delivery.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    The amino acid must be converted before this sensor route works.
    primary_references
    SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29123071/ · DOI 10.1126/science.aao3265
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 252–258

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human doxycycline-regulated MAT2A cells; starvation and repletion. · source_derived_draft · unverified_draft

    ## methionine-mat2a-sensor-coupling The amino acid must be converted before this sensor route works. Acute MAT2A depletion reduced mTORC1 responsiveness to methionine while largely preserving responsiveness to supplied SAM. Model: Human doxycycline-regulated MAT2A cells; starvation and repletion. Limitations: Cellular SAM addition is not evidence for equivalent oral delivery. Evidence access: Primary full text SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29123071/ · DOI 10.1126/science.aao3265
    Complete structured claim and evidence

  3. Human MAT2A formed S-adenosylmethionine before rapid triphosphate hydrolysis and product release in the kinetic study.

    Human methionine adenosyltransferase 2A / MAT2A → S-Adenosyl-L-methionine source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
    experimental_model
    Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
    exposure
    ATP/methionine reactions and PNPNP ligand complexes
    limitations
    Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
    nutrient_topic
    Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
    organism
    Human recombinant enzyme
    plain_language
    Making the methyl donor SAM is coupled to ATP-derived phosphate chemistry.
    primary_references
    [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    tissue_or_cell_type
    Purified MAT2A active site

    Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 633–644

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft

    ### phosphorus-mat-sam Human MAT2A formed S-adenosylmethionine before rapid triphosphate hydrolysis and product release in the kinetic study. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making the methyl donor SAM is coupled to ATP-derived phosphate chemistry. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    Complete structured claim and evidence

What acts on it

  1. The human MAT2A inhibitor-bound structure contained two magnesium ions coordinating phosphate groups at the catalytic site.

    Mg2+ → Human methionine adenosyltransferase 2A / MAT2A source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human MAT2A structure with nonhydrolyzable imidotriphosphate and methylthioadenosine.
    limitations
    Inhibitor-bound structural contacts are not a dietary magnesium dose-response.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    SAM-making chemistry depends on correctly organized metal/phosphate contacts.
    primary_references
    Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 132–138

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MAT2A structure with nonhydrolyzable imidotriphosphate and methylthioadenosine. · source_derived_draft · unverified_draft

    ## methionine-mat-magnesium SAM-making chemistry depends on correctly organized metal/phosphate contacts. The human MAT2A inhibitor-bound structure contained two magnesium ions coordinating phosphate groups at the catalytic site. Model: Human MAT2A structure with nonhydrolyzable imidotriphosphate and methylthioadenosine. Limitations: Inhibitor-bound structural contacts are not a dietary magnesium dose-response. Evidence access: Primary abstract Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998
    Complete structured claim and evidence

  2. An essential potassium ion contacted the beta-phosphoryl oxygen in the human MAT2A catalytic-site ligand structure.

    Potassium ion → Human methionine adenosyltransferase 2A / MAT2A source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Purified human MAT2A crystallography and kinetic study.
    limitations
    Does not show that extra potassium increases methylation in potassium-replete humans.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Potassium participates directly in the enzyme chemistry.
    primary_references
    Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 140–146

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MAT2A crystallography and kinetic study. · source_derived_draft · unverified_draft

    ## methionine-mat-potassium Potassium participates directly in the enzyme chemistry. An essential potassium ion contacted the beta-phosphoryl oxygen in the human MAT2A catalytic-site ligand structure. Model: Purified human MAT2A crystallography and kinetic study. Limitations: Does not show that extra potassium increases methylation in potassium-replete humans. Evidence access: Primary abstract Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33656855/ · DOI 10.1021/acs.biochem.0c00998
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Methionine-starvation-induced SAM depletion increased MAT2A expression through METTL16-dependent splicing involving a conserved 3-prime-UTR hairpin.

    Human RNA methyltransferase / METTL16 → Splicing of the retained human MAT2A intron source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human MAT2A reporter/cell and RNA-biochemistry experiments.
    limitations
    Increased transcript processing does not replace the missing methionine substrate.
    nutrient_topic
    L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Methionine
    plain_language
    Low methyl-donor availability can increase production capacity through RNA processing.
    primary_references
    The U6 snRNA m6A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28525753/ · DOI 10.1016/j.cell.2017.05.003
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Methionine: transport, methylation, sulfur metabolism and cross-nutrient mechanisms (2026-09-19) · lines 260–266

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MAT2A reporter/cell and RNA-biochemistry experiments. · source_derived_draft · unverified_draft

    ## methionine-mettl16-feedback Low methyl-donor availability can increase production capacity through RNA processing. Methionine-starvation-induced SAM depletion increased MAT2A expression through METTL16-dependent splicing involving a conserved 3-prime-UTR hairpin. Model: Human MAT2A reporter/cell and RNA-biochemistry experiments. Limitations: Increased transcript processing does not replace the missing methionine substrate. Evidence access: Primary abstract The U6 snRNA m6A Methyltransferase METTL16 Regulates SAM Synthetase Intron Retention. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28525753/ · DOI 10.1016/j.cell.2017.05.003
    Complete structured claim and evidence

  2. Two Mg2+ ions chelated the alpha- and gamma-phosphoryl groups of PNPNP in the human MAT2A structure.

    Mg2+ → Diimido triphosphate / PNPNP, experimental MAT2A ligand source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
    experimental_model
    Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
    exposure
    ATP/methionine reactions and PNPNP ligand complexes
    limitations
    Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
    nutrient_topic
    Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
    organism
    Human recombinant enzyme
    plain_language
    Magnesium helped position the experimental phosphate-chain mimic at the enzyme site.
    primary_references
    [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    tissue_or_cell_type
    Purified MAT2A active site

    Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 659–670

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft

    ### phosphorus-mat-magnesium Two Mg2+ ions chelated the alpha- and gamma-phosphoryl groups of PNPNP in the human MAT2A structure. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helped position the experimental phosphate-chain mimic at the enzyme site. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    Complete structured claim and evidence

  3. After SAM formation, MAT2A rapidly hydrolyzed the beta–gamma bond of triphosphate and released phosphate and pyrophosphate.

    Inorganic triphosphate → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
    experimental_model
    Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
    exposure
    ATP/methionine reactions and PNPNP ligand complexes
    limitations
    Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
    nutrient_topic
    Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
    organism
    Human recombinant enzyme
    plain_language
    ATP’s phosphate chain is processed into two separately tracked products.
    primary_references
    [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    tissue_or_cell_type
    Purified MAT2A active site

    Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 646–657

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft

    ### phosphorus-mat-pi After SAM formation, MAT2A rapidly hydrolyzed the beta–gamma bond of triphosphate and released phosphate and pyrophosphate. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP’s phosphate chain is processed into two separately tracked products. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    Complete structured claim and evidence

  4. The beta-phosphoryl oxygen of the MAT2A-bound PNPNP ligand contacted the essential potassium ion.

    Potassium ion → Diimido triphosphate / PNPNP, experimental MAT2A ligand source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
    experimental_model
    Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
    exposure
    ATP/methionine reactions and PNPNP ligand complexes
    limitations
    Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
    nutrient_topic
    Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
    organism
    Human recombinant enzyme
    plain_language
    Potassium and magnesium had distinct contacts in the same phosphate-handling active site.
    primary_references
    [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    tissue_or_cell_type
    Purified MAT2A active site

    Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 672–683

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft

    ### phosphorus-mat-potassium The beta-phosphoryl oxygen of the MAT2A-bound PNPNP ligand contacted the essential potassium ion. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium and magnesium had distinct contacts in the same phosphate-handling active site. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
    Complete structured claim and evidence

In the sources

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

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards