Component

Human phosphoglycerate dehydrogenase / PHGDH

Context-specific entity; species, compartment and exposure are stated on each claim.

6 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. Alanine substitutions at the predicted human PHGDH tetramer interface disrupted assembly, stability and activity for several tested ACT-domain residues.

    Human phosphoglycerate dehydrogenase / PHGDH → Human PHGDH folding and catalytic activity source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human recombinant variants; solution biochemistry with AlphaFold and molecular-dynamics model refinement.
    limitations
    The complete tetramer model is computationally derived; it is not an experimentally solved full-length crystal structure.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    The enzyme must fold and assemble correctly as well as receive its cofactor.
    primary_references
    On the quaternary structure of human D-3-phosphoglycerate dehydrogenase. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39012001/ · DOI 10.1002/pro.5089
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 22–28

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant variants; solution biochemistry with AlphaFold and molecular-dynamics model refinement. · source_derived_draft · unverified_draft

    ## l-serine-phgdh-assembly The enzyme must fold and assemble correctly as well as receive its cofactor. Alanine substitutions at the predicted human PHGDH tetramer interface disrupted assembly, stability and activity for several tested ACT-domain residues. Model: Human recombinant variants; solution biochemistry with AlphaFold and molecular-dynamics model refinement. Limitations: The complete tetramer model is computationally derived; it is not an experimentally solved full-length crystal structure. Evidence access: Primary abstract On the quaternary structure of human D-3-phosphoglycerate dehydrogenase. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39012001/ · DOI 10.1002/pro.5089
    Complete structured claim and evidence

  2. Patients with inherited PHGDH deficiency had low plasma and cerebrospinal-fluid serine, variably low glycine, microcephaly, seizures and severe developmental impairment.

    Human phosphoglycerate dehydrogenase / PHGDH → L-Serine source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Five-patient treatment follow-up in a rare inherited disorder.
    limitations
    This is not evidence that ordinary low dietary intake causes the same syndrome.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    An internal synthesis defect can create a clinically important shortage.
    primary_references
    Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 86–92

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Five-patient treatment follow-up in a rare inherited disorder. · source_derived_draft · unverified_draft

    ## l-serine-phgdh-deficiency An internal synthesis defect can create a clinically important shortage. Patients with inherited PHGDH deficiency had low plasma and cerebrospinal-fluid serine, variably low glycine, microcephaly, seizures and severe developmental impairment. Model: Five-patient treatment follow-up in a rare inherited disorder. Limitations: This is not evidence that ordinary low dietary intake causes the same syndrome. Evidence access: Primary abstract Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
    Complete structured claim and evidence

  3. Human PHGDH catalyzes the NAD+-dependent oxidation of 3-phosphoglycerate to phosphohydroxypyruvate, the first step of phosphorylated serine biosynthesis.

    Human phosphoglycerate dehydrogenase / PHGDH → 3-Phosphohydroxypyruvate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Recombinant human PHGDH catalytic-domain structure and enzyme assays.
    limitations
    The truncated dimeric structure does not define the complete native oligomer.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    A glycolysis intermediate can be diverted into serine production.
    primary_references
    Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). · 2017 · https://pubmed.ncbi.nlm.nih.gov/29262655/ · DOI 10.18632/oncotarget.22327

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 14–20

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human PHGDH catalytic-domain structure and enzyme assays. · source_derived_draft · unverified_draft

    ## l-serine-phgdh-reaction A glycolysis intermediate can be diverted into serine production. Human PHGDH catalyzes the NAD+-dependent oxidation of 3-phosphoglycerate to phosphohydroxypyruvate, the first step of phosphorylated serine biosynthesis. Model: Recombinant human PHGDH catalytic-domain structure and enzyme assays. Limitations: The truncated dimeric structure does not define the complete native oligomer. Evidence access: Primary abstract Structural insights into the enzymatic activity and potential substrate promiscuity of human 3-phosphoglycerate dehydrogenase (PHGDH). · 2017 · https://pubmed.ncbi.nlm.nih.gov/29262655/ · DOI 10.18632/oncotarget.22327
    Complete structured claim and evidence

What acts on it

  1. Purified NADHX species inhibited recombinant human PHGDH, supporting direct inhibition as an explanation for the serine-synthesis defect in NAXD-deficient cells.

    Hydrated NADH / NADHX → Human phosphoglycerate dehydrogenase / PHGDH source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate.
    limitations
    NADHX is chemically damaged NADH, not simply a low NAD+ concentration.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Repair of a niacin-derived cofactor protects a separate amino-acid pathway.
    primary_references
    Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 126–132

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate. · source_derived_draft · unverified_draft

    ## l-serine-nadhx-inhibition Repair of a niacin-derived cofactor protects a separate amino-acid pathway. Purified NADHX species inhibited recombinant human PHGDH, supporting direct inhibition as an explanation for the serine-synthesis defect in NAXD-deficient cells. Model: Recombinant enzyme assays, including 40 micromolar 3-phosphoglycerate substrate. Limitations: NADHX is chemically damaged NADH, not simply a low NAD+ concentration. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. NAXD loss caused NADHX accumulation and impaired de novo serine synthesis in human HAP1 cells under galactose stress and in patient-derived fibroblasts.

    Human NAD(P)HX dehydratase / NAXD → Hydrated NADH / NADHX source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human knockout cells, patient fibroblasts and isotope tracing.
    limitations
    The impairment depended on culture conditions and was more pronounced under galactose stress.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Damaged cofactor can block a pathway even when the enzyme is still present.
    primary_references
    Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 118–124

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human knockout cells, patient fibroblasts and isotope tracing. · source_derived_draft · unverified_draft

    ## l-serine-naxd-block Damaged cofactor can block a pathway even when the enzyme is still present. NAXD loss caused NADHX accumulation and impaired de novo serine synthesis in human HAP1 cells under galactose stress and in patient-derived fibroblasts. Model: Human knockout cells, patient fibroblasts and isotope tracing. Limitations: The impairment depended on culture conditions and was more pronounced under galactose stress. Evidence access: Primary full text Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39789421/ · DOI 10.1186/s11658-024-00681-8
    Complete structured claim and evidence

  2. Amino-acid therapy over 3–7.5 years reduced seizure frequency in all five reported patients, with two becoming seizure-free; developmental progress was reported in only one early-treated patient.

    L-Serine → Seizure outcomes during amino-acid treatment of PHGDH deficiency source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Uncontrolled follow-up using different serine/glycine treatment regimens.
    limitations
    Small heterogeneous case series; no general supplement dose or guaranteed developmental rescue follows.
    nutrient_topic
    L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine
    plain_language
    Restoring supply can help some outcomes without reversing every consequence.
    primary_references
    Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 94–100

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Uncontrolled follow-up using different serine/glycine treatment regimens. · source_derived_draft · unverified_draft

    ## l-serine-phgdh-treatment Restoring supply can help some outcomes without reversing every consequence. Amino-acid therapy over 3–7.5 years reduced seizure frequency in all five reported patients, with two becoming seizure-free; developmental progress was reported in only one early-treated patient. Model: Uncontrolled follow-up using different serine/glycine treatment regimens. Limitations: Small heterogeneous case series; no general supplement dose or guaranteed developmental rescue follows. Evidence access: Primary abstract Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12118526/ · DOI 10.1023/a:1015624726822
    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