Component

NOS-dependent nitric oxide production, model specified

NOS-dependent nitric oxide production, model specified. Species, exposure and limitations are retained in each linked 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. N-nitro-L-arginine methyl ester attenuated the relaxation, implicating nitric-oxide synthase in it.

    NOS-dependent nitric oxide production, model specified → Rat thoracic aortic ring tension source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    duration
    Not stated here
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Rat
    exposure
    Nattokinase with L-NAME
    limitations
    Recorded under a blocked pathway: the finding is what happens when NOS is inhibited. The isoform is not identified, and indomethacin was tested in the same design without its result being separable from the abstract.
    organism
    Rat
    plain_language
    N-nitro-L-arginine methyl ester attenuated the relaxation, implicating nitric-oxide synthase in it.
    primary_references
    Mechanisms of Nattokinase in protection of cerebral ischemia. (2014) https://pubmed.ncbi.nlm.nih.gov/25446567/ DOI: 10.1016/j.ejphar.2014.10.024
    route
    Ex vivo
    tissue
    Thoracic aortic ring
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Nattokinase: what the purified enzyme cleaves, what survives being eaten, and the gap between the two (2026-09-23) · lines 411–411

    Original AI-assisted curation built from a supplied entity-first document of 105 entities and 129 claims. Every reference in that document was resolved against live PubMed with its abstract read and its DOI cross-checked on 2026-09-23, and the EFSA novel-food opinion was retrieved and read in full. That check corrected two PMIDs that pointed at unrelated papers, two DOIs, and two papers recorded as carrying no erratum that do carry one; it also reversed three findings the supplied document had stated backwards. Two papers carry a published correction, recorded as such and not as a retraction. Three sources are not indexed in PubMed and are cited by what they have. Laboratory lineages are recorded, so the four papers from one group, the three from another and the two readings of a single applicant dossier cannot be counted as separate lines of support. Study-specific doses, units, populations and limitations retained; activity units are never converted between systems. Not publisher full text. · supports · Rat · source_derived_draft · unverified_draft

    N-nitro-L-arginine methyl ester attenuated the relaxation, implicating nitric-oxide synthase in it.
    Complete structured claim and evidence

What acts on it

  1. ASL deficiency reduced nitric-oxide synthesis in the studied humans and mice.

    ASL-deficient state, human or mouse model specified → NOS-dependent nitric oxide production, model specified source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/citrulline-research/22081021.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f9f02564dadd246299fe5eded3ddb08e3c68f08d27cae8b16f2506fe9eaf68b", "start_char": 0, "end_char": 1137, "text_sha256": "2f9f02564dadd246299fe5eded3ddb08e3c68f08d27cae8b16f2506fe9eaf68b"}
    experimental_model
    Patient vascular testing, hypomorphic mice and molecular experiments
    exposure
    ASL loss; extracellular arginine; nitrite or NO donor interventions
    limitations
    Rare genetic deficiency; molecular scaffolding is distinct from supplying enough circulating arginine.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human ASL deficiency and Asl-deficient mice, model specified
    plain_language
    An intact downstream enzyme matters to the NO pathway.
    primary_references
    [citrulline-p22081021] Requirement of argininosuccinate lyase for systemic nitric oxide production. (2011). https://pubmed.ncbi.nlm.nih.gov/22081021/ DOI: 10.1038/nm.2544
    tissue_or_cell_type
    Arginine synthesis, NOS-associated protein complex and vasculature
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 619–630

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient vascular testing, hypomorphic mice and molecular experiments · source_derived_draft · unverified_draft

    ### citrulline-asl-no-low ASL deficiency reduced nitric-oxide synthesis in the studied humans and mice. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intact downstream enzyme matters to the NO pathway. organism: Human ASL deficiency and Asl-deficient mice, model specified tissue_or_cell_type: Arginine synthesis, NOS-associated protein complex and vasculature experimental_model: Patient vascular testing, hypomorphic mice and molecular experiments limitations: Rare genetic deficiency; molecular scaffolding is distinct from supplying enough circulating arginine. exposure: ASL loss; extracellular arginine; nitrite or NO donor interventions evidence_span: {"source_cache": "artifacts/citrulline-research/22081021.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f9f02564dadd246299fe5eded3ddb08e3c68f08d27cae8b16f2506fe9eaf68b", "start_char": 0, "end_char": 1137, "text_sha256": "2f9f02564dadd246299fe5eded3ddb08e3c68f08d27cae8b16f2506fe9eaf68b"} [citrulline-p22081021] Requirement of argininosuccinate lyase for systemic nitric oxide production. (2011). https://pubmed.ncbi.nlm.nih.gov/22081021/ DOI: 10.1038/nm.2544
    Complete structured claim and evidence

  2. ASS1 knockdown reduced basal and stimulated NO despite saturating arginine in the culture medium.

    Bovine endothelial ASS1 knockdown → NOS-dependent nitric oxide production, model specified source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/citrulline-research/14970240.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056", "start_char": 0, "end_char": 1589, "text_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056"}
    experimental_model
    RNA-interference and NO-donor rescue experiments
    exposure
    ASS1 knockdown despite saturating extracellular arginine
    limitations
    Bovine cell model; no claim that every human tissue exclusively uses regenerated arginine.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Bovine aortic endothelial cells
    plain_language
    Bulk substrate abundance did not compensate for impaired local recycling.
    primary_references
    [citrulline-p14970240] Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/14970240/ DOI: 10.1074/jbc.m308160200
    tissue_or_cell_type
    Citrulline recycling, NO synthesis and viability
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 658–669

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RNA-interference and NO-donor rescue experiments · source_derived_draft · unverified_draft

    ### citrulline-ass1-local-no ASS1 knockdown reduced basal and stimulated NO despite saturating arginine in the culture medium. Condition category: machinery_impairment nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bulk substrate abundance did not compensate for impaired local recycling. organism: Bovine aortic endothelial cells tissue_or_cell_type: Citrulline recycling, NO synthesis and viability experimental_model: RNA-interference and NO-donor rescue experiments limitations: Bovine cell model; no claim that every human tissue exclusively uses regenerated arginine. exposure: ASS1 knockdown despite saturating extracellular arginine evidence_span: {"source_cache": "artifacts/citrulline-research/14970240.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056", "start_char": 0, "end_char": 1589, "text_sha256": "7d7acfd232edfd5d968d7afcbaf80ea27807a4313b5a385c90fd11b437403056"} [citrulline-p14970240] Argininosuccinate synthase expression is required to maintain nitric oxide production and cell viability in aortic endothelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/14970240/ DOI: 10.1074/jbc.m308160200
    Complete structured claim and evidence

  3. Ascorbate had no additional effect at high BH4 or after sepiapterin raised cellular BH4.

    Tetrahydrobiopterin / BH4 → NOS-dependent nitric oxide production, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}
    experimental_model
    Cell exposure and recombinant-enzyme assays
    exposure
    Ascorbate loading; BH4 or sepiapterin comparisons
    limitations
    Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Porcine aortic endothelial cells and bovine eNOS
    plain_language
    The benefit depended on the starting cofactor conditions.
    primary_references
    [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    tissue_or_cell_type
    BH4 availability and NO bioactivity

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 723–734

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

    ### citrulline-vitaminc-bh4-saturation Ascorbate had no additional effect at high BH4 or after sepiapterin raised cellular BH4. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The benefit depended on the starting cofactor conditions. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    Complete structured claim and evidence

  4. Ascorbate increased arginine-to-citrulline conversion and NO-related output in porcine endothelial cells.

    L-Ascorbate → NOS-dependent nitric oxide production, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"}
    experimental_model
    Cell exposure and recombinant-enzyme assays
    exposure
    Ascorbate loading; BH4 or sepiapterin comparisons
    limitations
    Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Porcine aortic endothelial cells and bovine eNOS
    plain_language
    Protecting the machinery can matter as well as supplying arginine.
    primary_references
    [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    tissue_or_cell_type
    BH4 availability and NO bioactivity

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 710–721

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

    ### citrulline-vitaminc-no Ascorbate increased arginine-to-citrulline conversion and NO-related output in porcine endothelial cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protecting the machinery can matter as well as supplying arginine. organism: Porcine aortic endothelial cells and bovine eNOS tissue_or_cell_type: BH4 availability and NO bioactivity experimental_model: Cell exposure and recombinant-enzyme assays limitations: Preclinical experiments; not proof that vitamin C is needed as a co-supplement with citrulline. exposure: Ascorbate loading; BH4 or sepiapterin comparisons evidence_span: {"source_cache": "artifacts/citrulline-research/10749876.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed", "start_char": 0, "end_char": 1519, "text_sha256": "10605941fa542bd62ed4ee0fb042ea7569f3ab619f1cb893b54d7e62386712ed"} [citrulline-p10749876] Ascorbic acid enhances endothelial nitric-oxide synthase activity by increasing intracellular tetrahydrobiopterin. (2000). https://pubmed.ncbi.nlm.nih.gov/10749876/ DOI: 10.1074/jbc.m002248200
    Complete structured claim and evidence

  5. In-vitro and in-vivo experiments identified ADMA as an endogenous inhibitor of NO synthesis.

    Asymmetric dimethylarginine / ADMA → NOS-dependent nitric oxide production, model specified source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Experimental NO assays and human renal-failure observations.
    limitations
    The abstract does not isolate a single NOS isoform.
    nutrient_topic
    L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
    plain_language
    An internal inhibitor can limit the pathway even when arginine is present.
    primary_references
    Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1347093/ · DOI 10.1016/0140-6736(92)90865-z

    L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 94–100

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Experimental NO assays and human renal-failure observations. · source_derived_draft · unverified_draft

    ## arg-adma-nos An internal inhibitor can limit the pathway even when arginine is present. In-vitro and in-vivo experiments identified ADMA as an endogenous inhibitor of NO synthesis. Model: Experimental NO assays and human renal-failure observations. Limitations: The abstract does not isolate a single NOS isoform. Evidence access: Primary abstract Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1347093/ · DOI 10.1016/0140-6736(92)90865-z
    Complete structured claim and evidence

In the sources

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

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