Component

Human pyrroline-5-carboxylate synthase / ALDH18A1

Human pyrroline-5-carboxylate synthase / ALDH18A1. Species, exposure and limitations are retained in each linked claim.

5 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 P5CS links glutamate to P5C synthesis through ATP- and NADPH-dependent chemistry.

    Human pyrroline-5-carboxylate synthase / ALDH18A1 → Delta-1-pyrroline-5-carboxylate / P5C source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"}
    experimental_model
    Patient genetics and recombinant variant expression
    exposure
    ALDH18A1 R84Q compared with wild-type isoforms
    limitations
    Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human, two siblings and mammalian expression systems
    plain_language
    This supplies a precursor route connected to ornithine and arginine production.
    primary_references
    [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
    tissue_or_cell_type
    Mitochondrial P5CS and circulating amino acids

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 294–305

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient genetics and recombinant variant expression · source_derived_draft · unverified_draft

    ### citrulline-p5cs-reaction Human P5CS links glutamate to P5C synthesis through ATP- and NADPH-dependent chemistry. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: This supplies a precursor route connected to ornithine and arginine production. organism: Human, two siblings and mammalian expression systems tissue_or_cell_type: Mitochondrial P5CS and circulating amino acids experimental_model: Patient genetics and recombinant variant expression limitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype. exposure: ALDH18A1 R84Q compared with wild-type isoforms evidence_span: {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"} [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
    Complete structured claim and evidence

What acts on it

  1. P5CS requires NADPH for its reductive step in glutamate-to-P5C synthesis.

    NADPH → Human pyrroline-5-carboxylate synthase / ALDH18A1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"}
    experimental_model
    Patient genetics and recombinant variant expression
    exposure
    ALDH18A1 R84Q compared with wild-type isoforms
    limitations
    Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human, two siblings and mammalian expression systems
    plain_language
    A niacin-derived electron donor participates upstream of citrulline.
    primary_references
    [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
    tissue_or_cell_type
    Mitochondrial P5CS and circulating amino acids

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 307–318

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient genetics and recombinant variant expression · source_derived_draft · unverified_draft

    ### citrulline-p5cs-nadph P5CS requires NADPH for its reductive step in glutamate-to-P5C synthesis. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: A niacin-derived electron donor participates upstream of citrulline. organism: Human, two siblings and mammalian expression systems tissue_or_cell_type: Mitochondrial P5CS and circulating amino acids experimental_model: Patient genetics and recombinant variant expression limitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype. exposure: ALDH18A1 R84Q compared with wild-type isoforms evidence_span: {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"} [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. A separate study found NADK2 loss depleted mitochondrial NADPH, limited P5C generation and made tested mammalian cells dependent on exogenous proline for growth.

    NADK2 → P5C production during NADK2-dependent proline synthesis source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mammalian NADK2-deletion cell models; primary abstract.
    limitations
    Detailed model and exposure differences remain distinct; the two publications are not duplicate evidence records from one experiment.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A second research group found the same synthesis vulnerability.
    primary_references
    Mitochondrial NADP+ is essential for proline biosynthesis during cell growth. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33833463/ · DOI 10.1038/s42255-021-00374-y
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 78–84

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mammalian NADK2-deletion cell models; primary abstract. · source_derived_draft · unverified_draft

    ## l-proline-nadk2-independent-study A second research group found the same synthesis vulnerability. A separate study found NADK2 loss depleted mitochondrial NADPH, limited P5C generation and made tested mammalian cells dependent on exogenous proline for growth. Model: Mammalian NADK2-deletion cell models; primary abstract. Limitations: Detailed model and exposure differences remain distinct; the two publications are not duplicate evidence records from one experiment. Evidence access: Primary abstract Mitochondrial NADP+ is essential for proline biosynthesis during cell growth. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33833463/ · DOI 10.1038/s42255-021-00374-y
    Complete structured claim and evidence

  2. NADK2 deletion reduced glutamine-derived proline synthesis; mitochondrial NADP(H) was needed for the P5CS step reducing glutamate toward P5C.

    NADK2 → L-Proline source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cell deletion, isotope tracing and rescue experiments.
    limitations
    The limiting step was cofactor-dependent synthesis, not a demonstrated lack of glutamine in the diet.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Proline production needs reducing power in the right compartment.
    primary_references
    Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 62–68

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

    ## l-proline-nadk2-proline Proline production needs reducing power in the right compartment. NADK2 deletion reduced glutamine-derived proline synthesis; mitochondrial NADP(H) was needed for the P5CS step reducing glutamate toward P5C. Model: Human cell deletion, isotope tracing and rescue experiments. Limitations: The limiting step was cofactor-dependent synthesis, not a demonstrated lack of glutamine in the diet. Evidence access: Primary full text Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    Complete structured claim and evidence

  3. The two R84Q siblings had hypocitrullinemia with low ornithine, arginine and proline; the variant strongly reduced expressed P5CS activity.

    Human ALDH18A1 / P5CS R84Q variant → Circulating citrulline concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"}
    experimental_model
    Patient genetics and recombinant variant expression
    exposure
    ALDH18A1 R84Q compared with wild-type isoforms
    limitations
    Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human, two siblings and mammalian expression systems
    plain_language
    Low citrulline can arise from a defective upstream enzyme.
    primary_references
    [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
    tissue_or_cell_type
    Mitochondrial P5CS and circulating amino acids
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 320–331

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient genetics and recombinant variant expression · source_derived_draft · unverified_draft

    ### citrulline-p5cs-low-citrulline The two R84Q siblings had hypocitrullinemia with low ornithine, arginine and proline; the variant strongly reduced expressed P5CS activity. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low citrulline can arise from a defective upstream enzyme. organism: Human, two siblings and mammalian expression systems tissue_or_cell_type: Mitochondrial P5CS and circulating amino acids experimental_model: Patient genetics and recombinant variant expression limitations: Rare inherited enzyme disorder; does not imply low dietary citrulline caused the clinical phenotype. exposure: ALDH18A1 R84Q compared with wild-type isoforms evidence_span: {"source_cache": "artifacts/citrulline-research/11092761.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2", "start_char": 0, "end_char": 1688, "text_sha256": "09706fd9ec135c472473decaa612e06b3e5aa021c9b1493d77daf4fe98b8d5d2"} [citrulline-p11092761] Hyperammonemia with reduced ornithine, citrulline, arginine and proline: a new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. (2000). https://pubmed.ncbi.nlm.nih.gov/11092761/ DOI: 10.1093/hmg/9.19.2853
    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