Component

SHMT2

Independent protein record; interpretation is limited by each linked claim and its study context.

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. Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.

    SHMT2 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    PLP (B6) and THF (folate) cooperate in one reaction.
    experimental_model
    Purified human SHMT1 and SHMT2; structures and solution oligomerization
    limitations
    Reaction is reversible; assembly assays do not establish flux in every cell.
    nutrient_topic
    Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
    organism
    Homo sapiens
    plain_language
    The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.
    primary_references
    [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 614–624

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft

    ### b6-met-shmt2-onecarbon Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
    Complete structured claim and evidence

  2. SHMT2 silencing combined with removal of extracellular glycine halted LOX IMVI proliferation; adding glycine restored growth whereas formate did not.

    SHMT2 → Human LOX IMVI cell proliferation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human melanoma cultures with shRNA and nutrient withdrawal/rescue.
    limitations
    A combined manipulation; not proof that ordinary dietary glycine alone controls a tumor.
    nutrient_topic
    Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Glycine
    plain_language
    Removing both synthesis and external supply exposed a glycine dependency.
    primary_references
    Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 154–160

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human melanoma cultures with shRNA and nutrient withdrawal/rescue. · source_derived_draft · unverified_draft

    ## glycine-shmt2-glycine-dependence Removing both synthesis and external supply exposed a glycine dependency. SHMT2 silencing combined with removal of extracellular glycine halted LOX IMVI proliferation; adding glycine restored growth whereas formate did not. Model: Human melanoma cultures with shRNA and nutrient withdrawal/rescue. Limitations: A combined manipulation; not proof that ordinary dietary glycine alone controls a tumor. Evidence access: Primary full text Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22628656/ · DOI 10.1126/science.1218595
    Complete structured claim and evidence

  3. Catalytic SHMT2 loss in human cells impaired mitochondrial tRNA modification and caused preferential ribosome stalling at AAG lysine and UUG leucine codons.

    SHMT2 → Human mitochondrial translation at lysine and leucine codons source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human SHMT2 knockout and mitochondrial ribosome profiling.
    limitations
    The methyl-donor route was mechanistically inferred alongside measured modification and translation defects.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Serine-linked folate chemistry helps mitochondria read particular codons.
    primary_references
    Mitochondrial translation requires folate-dependent tRNA methylation. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29364879/ · DOI 10.1038/nature25460
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 174–180

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SHMT2 knockout and mitochondrial ribosome profiling. · source_derived_draft · unverified_draft

    ## l-serine-shmt2-translation Serine-linked folate chemistry helps mitochondria read particular codons. Catalytic SHMT2 loss in human cells impaired mitochondrial tRNA modification and caused preferential ribosome stalling at AAG lysine and UUG leucine codons. Model: Human SHMT2 knockout and mitochondrial ribosome profiling. Limitations: The methyl-donor route was mechanistically inferred alongside measured modification and translation defects. Evidence access: Primary abstract Mitochondrial translation requires folate-dependent tRNA methylation. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29364879/ · DOI 10.1038/nature25460
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Adding PLP shifted purified human SHMT2 from dimers toward tetramers.

    PLP → SHMT2 tetramer assembly source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Purified human SHMT1 and SHMT2; structures and solution oligomerization
    limitations
    In-vitro cofactor titration; no dietary deficiency threshold was tested.
    nutrient_topic
    Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
    organism
    Homo sapiens
    plain_language
    Active B6 also helps assemble SHMT2.
    primary_references
    [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 626–635

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft

    ### b6-met-shmt2-assembly Adding PLP shifted purified human SHMT2 from dimers toward tetramers. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active B6 also helps assemble SHMT2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: In-vitro cofactor titration; no dietary deficiency threshold was tested. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
    Complete structured claim and evidence

  2. SLC25A38 loss reduced deuterated-serine incorporation into glycine and glycine-derived glutathione under low-B6 conditions.

    Human SLC25A38 → Serine-derived glycine synthesis in human K562 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 K562 knockout, isotope tracing and controlled B6 culture conditions.
    limitations
    Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38.
    nutrient_topic
    Glycine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Glycine
    plain_language
    A mitochondrial cofactor problem reduced the cell's ability to make glycine.
    primary_references
    SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Glycine: supply, one-carbon allocation, receptors and cross-nutrient mechanisms (2026-09-19) · lines 114–120

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human K562 knockout, isotope tracing and controlled B6 culture conditions. · source_derived_draft · unverified_draft

    ## glycine-s38-glycine-synthesis A mitochondrial cofactor problem reduced the cell's ability to make glycine. SLC25A38 loss reduced deuterated-serine incorporation into glycine and glycine-derived glutathione under low-B6 conditions. Model: Human K562 knockout, isotope tracing and controlled B6 culture conditions. Limitations: Tracing reflects pathway flux; it does not establish direct PLP transport by SLC25A38. Evidence access: Primary full text SLC25A38 is required for mitochondrial pyridoxal 5'-phosphate (PLP) accumulation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39856062/ · DOI 10.1038/s41467-025-56130-3
    Complete structured claim and evidence

  3. SFXN1-null human cells had impaired glycine and purine synthesis; loss of both SFXN1 and SFXN3 caused stronger defects, including dependence on exogenous glycine.

    Human sideroflexin 1 / SFXN1 → Glycine and purine synthesis in human SFXN1-deficient cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human cell single and double knockout comparisons.
    limitations
    Related transporters provide redundancy; this is not a demonstrated dietary serine deficiency.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Transport capacity can limit another amino acid and nucleotide production.
    primary_references
    SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 150–156

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell single and double knockout comparisons. · source_derived_draft · unverified_draft

    ## l-serine-sfxn1-loss Transport capacity can limit another amino acid and nucleotide production. SFXN1-null human cells had impaired glycine and purine synthesis; loss of both SFXN1 and SFXN3 caused stronger defects, including dependence on exogenous glycine. Model: Human cell single and double knockout comparisons. Limitations: Related transporters provide redundancy; this is not a demonstrated dietary serine deficiency. Evidence access: Primary abstract SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30442778/ · DOI 10.1126/science.aat9528
    Complete structured claim and evidence

  4. Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1.

    (2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Purified human enzyme kinetic assay
    limitations
    Mouse Tha1 specialization should not be assigned to a human THA1 enzyme.
    organism
    Homo sapiens
    plain_language
    SHMT2 provides another demonstrated aldolase activity.
    primary_references
    [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
    tissue_or_cell_type
    Mitochondrial enzyme tested in vitro

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 187–195

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme kinetic assay · source_derived_draft · unverified_draft

    ### shmt2-html-cleavage Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1. Plain language: SHMT2 provides another demonstrated aldolase activity. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial enzyme tested in vitro experimental_model: Purified human enzyme kinetic assay limitations: Mouse Tha1 specialization should not be assigned to a human THA1 enzyme. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
    Complete structured claim and evidence

  5. SHMT2-null Jurkat cells failed to maintain normal mitochondrial formylmethionyl-tRNA pools.

    Human SHMT2 gene → Mitochondrial formylmethionyl-tRNA source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    CRISPR and tRNA assays
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Several downstream mitochondrial consequences may coexist.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    Mitochondrial serine breakdown helps prepare the tRNA that starts translation.
    primary_references
    [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    tissue_or_cell_type
    Jurkat cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1109–1119

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR and tRNA assays · source_derived_draft · unverified_draft

    ### shmt2-loss-formyltrna SHMT2-null Jurkat cells failed to maintain normal mitochondrial formylmethionyl-tRNA pools. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial serine breakdown helps prepare the tRNA that starts translation. organism: Homo sapiens tissue_or_cell_type: Jurkat cells experimental_model: CRISPR and tRNA assays limitations: Several downstream mitochondrial consequences may coexist. exposure: Assay conditions described in the linked primary study. [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    Complete structured claim and evidence

  6. SHMT2 deletion reduced synthesis of mitochondrially encoded proteins while cytosolic protein labeling was preserved.

    Human SHMT2 gene → Mitochondrial protein translation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Radiolabeled protein synthesis
    exposure
    Assay conditions described in the linked primary study.
    limitations
    Cell-line response; no clinical supplementation conclusion.
    nutrient_topic
    Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
    organism
    Homo sapiens
    plain_language
    The translation defect was concentrated in mitochondria.
    primary_references
    [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    tissue_or_cell_type
    Jurkat cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1121–1131

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled protein synthesis · source_derived_draft · unverified_draft

    ### shmt2-loss-mito-translation SHMT2 deletion reduced synthesis of mitochondrially encoded proteins while cytosolic protein labeling was preserved. Condition category: machinery_impairment nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The translation defect was concentrated in mitochondria. organism: Homo sapiens tissue_or_cell_type: Jurkat cells experimental_model: Radiolabeled protein synthesis limitations: Cell-line response; no clinical supplementation conclusion. exposure: Assay conditions described in the linked primary study. [minton-2018] Serine Catabolism by SHMT2 Is Required for Proper Mitochondrial Translation Initiation and Maintenance of Formylmethionyl-tRNAs (2018). https://pubmed.ncbi.nlm.nih.gov/29452640/ DOI: 10.1016/j.molcel.2018.01.024
    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.

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