Component

Human glutamate-5-semialdehyde dehydrogenase / ALDH4A1

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

4 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. The human ALDH4A1 S352L disease-associated variant abolished catalytic activity and NAD+ binding, with a major rearrangement of the catalytic loop.

    Human glutamate-5-semialdehyde dehydrogenase / ALDH4A1 → Human ALDH4A1 S352L catalytic function source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Recombinant human mutant/wild-type structures and kinetic analysis.
    limitations
    This tests one inherited variant and does not establish a nutrient-addition rescue.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A structural defect can block proline breakdown even when substrate is plentiful.
    primary_references
    The three-dimensional structural basis of type II hyperprolinemia. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22516612/ · DOI 10.1016/j.jmb.2012.04.010
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 110–116

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human mutant/wild-type structures and kinetic analysis. · source_derived_draft · unverified_draft

    ## l-proline-aldh4-failure A structural defect can block proline breakdown even when substrate is plentiful. The human ALDH4A1 S352L disease-associated variant abolished catalytic activity and NAD+ binding, with a major rearrangement of the catalytic loop. Model: Recombinant human mutant/wild-type structures and kinetic analysis. Limitations: This tests one inherited variant and does not establish a nutrient-addition rescue. Evidence access: Primary abstract The three-dimensional structural basis of type II hyperprolinemia. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22516612/ · DOI 10.1016/j.jmb.2012.04.010
    Complete structured claim and evidence

  2. ALDH4A1 catalyzes NAD+-dependent oxidation of glutamate semialdehyde to glutamate, completing the second enzymatic stage of proline catabolism.

    Human glutamate-5-semialdehyde dehydrogenase / ALDH4A1 → L-Glutamate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human enzyme structures and kinetics; mouse enzyme complexes supplied high-resolution ligand views.
    limitations
    P5C and glutamate semialdehyde interconvert; the aldehyde is the oxidation substrate. Mouse ligand structures are not relabeled as human complexes.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A second enzyme turns the breakdown intermediate into glutamate.
    primary_references
    The three-dimensional structural basis of type II hyperprolinemia. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22516612/ · DOI 10.1016/j.jmb.2012.04.010

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 102–108

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme structures and kinetics; mouse enzyme complexes supplied high-resolution ligand views. · source_derived_draft · unverified_draft

    ## l-proline-aldh4-oxidation A second enzyme turns the breakdown intermediate into glutamate. ALDH4A1 catalyzes NAD+-dependent oxidation of glutamate semialdehyde to glutamate, completing the second enzymatic stage of proline catabolism. Model: Human enzyme structures and kinetics; mouse enzyme complexes supplied high-resolution ligand views. Limitations: P5C and glutamate semialdehyde interconvert; the aldehyde is the oxidation substrate. Mouse ligand structures are not relabeled as human complexes. Evidence access: Primary abstract The three-dimensional structural basis of type II hyperprolinemia. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22516612/ · DOI 10.1016/j.jmb.2012.04.010
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. P5C reacted with pyridoxal phosphate at pH 7.4 and 310 K to form three characterized adducts through condensation involving the PLP aldehyde group.

    Delta-1-pyrroline-5-carboxylate / P5C → PLP source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Cell-free NMR, chromatography and mass-spectrometry experiments motivated by hyperprolinemia type II.
    limitations
    This demonstrates chemistry under the tested conditions, not B6 depletion from an ordinary proline-containing meal.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    An accumulating proline intermediate can chemically trap active vitamin B6.
    primary_references
    Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200

    L-Proline: synthesis, collagen processing, redox metabolism 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 · Cell-free NMR, chromatography and mass-spectrometry experiments motivated by hyperprolinemia type II. · source_derived_draft · unverified_draft

    ## l-proline-p5c-b6-trapping An accumulating proline intermediate can chemically trap active vitamin B6. P5C reacted with pyridoxal phosphate at pH 7.4 and 310 K to form three characterized adducts through condensation involving the PLP aldehyde group. Model: Cell-free NMR, chromatography and mass-spectrometry experiments motivated by hyperprolinemia type II. Limitations: This demonstrates chemistry under the tested conditions, not B6 depletion from an ordinary proline-containing meal. Evidence access: Primary abstract Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200
    Complete structured claim and evidence

  2. The study was prompted by B6 deficiency and seizures in a child with hyperprolinemia type II; the adduct experiments support P5C-mediated cofactor inactivation as a contributing mechanism.

    Delta-1-pyrroline-5-carboxylate / P5C → Secondary vitamin B6 deficiency associated with hyperprolinemia type II source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human index-case context combined with in-vitro chemical mechanism.
    limitations
    Contribution to seizures is an interpretation; the paper does not establish controlled efficacy or a universal treatment dose.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A breakdown disorder can create a secondary cofactor problem.
    primary_references
    Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism 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 · Human index-case context combined with in-vitro chemical mechanism. · source_derived_draft · unverified_draft

    ## l-proline-p5c-clinical-link A breakdown disorder can create a secondary cofactor problem. The study was prompted by B6 deficiency and seizures in a child with hyperprolinemia type II; the adduct experiments support P5C-mediated cofactor inactivation as a contributing mechanism. Model: Human index-case context combined with in-vitro chemical mechanism. Limitations: Contribution to seizures is an interpretation; the paper does not establish controlled efficacy or a universal treatment dose. Evidence access: Primary abstract Pyridoxal phosphate de-activation by pyrroline-5-carboxylic acid. Increased risk of vitamin B6 deficiency and seizures in hyperprolinemia type II. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11134058/ · DOI 10.1074/jbc.M010860200
    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