Component

Human argininosuccinate synthetase 1 / ASS1

Human argininosuccinate synthetase 1 / ASS1. Species, exposure and limitations are retained in each linked claim.

7 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 ASS1 combines citrulline and aspartate to form argininosuccinate in an ATP-dependent reaction.

    Human argininosuccinate synthetase 1 / ASS1 → L-Argininosuccinate source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"}
    experimental_model
    Crystal structure and biochemical reaction characterization
    exposure
    Citrulline and aspartate bound to recombinant enzyme
    limitations
    Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human ASS1
    plain_language
    Citrulline needs a second amino acid and an enzyme-controlled step before it becomes arginine.
    primary_references
    [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
    tissue_or_cell_type
    Cytosolic arginine-regeneration reaction

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 125–136

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and biochemical reaction characterization · source_derived_draft · unverified_draft

    ### citrulline-ass1-reaction Human ASS1 combines citrulline and aspartate to form argininosuccinate in an ATP-dependent reaction. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrulline needs a second amino acid and an enzyme-controlled step before it becomes arginine. organism: Human ASS1 tissue_or_cell_type: Cytosolic arginine-regeneration reaction experimental_model: Crystal structure and biochemical reaction characterization limitations: Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established. exposure: Citrulline and aspartate bound to recombinant enzyme evidence_span: {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"} [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
    Complete structured claim and evidence

What acts on it

  1. Aspartate is a substrate of human ASS1 and was resolved with citrulline in the enzyme structure.

    L-Aspartate → Human argininosuccinate synthetase 1 / ASS1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"}
    experimental_model
    Crystal structure and biochemical reaction characterization
    exposure
    Citrulline and aspartate bound to recombinant enzyme
    limitations
    Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human ASS1
    plain_language
    Aspartate supplies part of the molecule built at this step.
    primary_references
    [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
    tissue_or_cell_type
    Cytosolic arginine-regeneration reaction

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 138–149

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and biochemical reaction characterization · source_derived_draft · unverified_draft

    ### citrulline-ass1-aspartate Aspartate is a substrate of human ASS1 and was resolved with citrulline in the enzyme structure. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Aspartate supplies part of the molecule built at this step. organism: Human ASS1 tissue_or_cell_type: Cytosolic arginine-regeneration reaction experimental_model: Crystal structure and biochemical reaction characterization limitations: Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established. exposure: Citrulline and aspartate bound to recombinant enzyme evidence_span: {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"} [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
    Complete structured claim and evidence

  2. The ASS1 reaction uses ATP cleavage to AMP and pyrophosphate.

    ATP → Human argininosuccinate synthetase 1 / ASS1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"}
    experimental_model
    Crystal structure and biochemical reaction characterization
    exposure
    Citrulline and aspartate bound to recombinant enzyme
    limitations
    Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human ASS1
    plain_language
    Arginine regeneration has an energy cost.
    primary_references
    [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
    tissue_or_cell_type
    Cytosolic arginine-regeneration reaction

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 151–162

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and biochemical reaction characterization · source_derived_draft · unverified_draft

    ### citrulline-ass1-energy The ASS1 reaction uses ATP cleavage to AMP and pyrophosphate. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Arginine regeneration has an energy cost. organism: Human ASS1 tissue_or_cell_type: Cytosolic arginine-regeneration reaction experimental_model: Crystal structure and biochemical reaction characterization limitations: Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established. exposure: Citrulline and aspartate bound to recombinant enzyme evidence_span: {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"} [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Mg-ATP almost completely protected human ASS1 against alpha-dicarbonyl inactivation, implicating arginine residues in its binding site.

    Magnesium-ATP complex → Human ASS1 magnesium-ATP binding source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/citrulline-research/2788888.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29b1553359d37a53c529b8a2b53ba646cca6b4b401ba7a9722e0e1f15510e676", "start_char": 0, "end_char": 1043, "text_sha256": "29b1553359d37a53c529b8a2b53ba646cca6b4b401ba7a9722e0e1f15510e676"}
    experimental_model
    Chemical modification and substrate protection of enzyme
    exposure
    Alpha-dicarbonyl modification with Mg-ATP protection
    limitations
    Protection assay identifies binding requirements; it is not a magnesium supplementation or depletion study.
    nutrient_topic
    Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
    organism
    Human ASS1
    plain_language
    The active energy substrate is linked to magnesium, but more magnesium is not automatically rate-limiting.
    primary_references
    [citrulline-p2788888] Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase. (1989). https://pubmed.ncbi.nlm.nih.gov/2788888/
    tissue_or_cell_type
    ATP-binding region

    Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 164–175

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical modification and substrate protection of enzyme · source_derived_draft · unverified_draft

    ### citrulline-ass1-mg-atp Mg-ATP almost completely protected human ASS1 against alpha-dicarbonyl inactivation, implicating arginine residues in its binding site. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active energy substrate is linked to magnesium, but more magnesium is not automatically rate-limiting. organism: Human ASS1 tissue_or_cell_type: ATP-binding region experimental_model: Chemical modification and substrate protection of enzyme limitations: Protection assay identifies binding requirements; it is not a magnesium supplementation or depletion study. exposure: Alpha-dicarbonyl modification with Mg-ATP protection evidence_span: {"source_cache": "artifacts/citrulline-research/2788888.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29b1553359d37a53c529b8a2b53ba646cca6b4b401ba7a9722e0e1f15510e676", "start_char": 0, "end_char": 1043, "text_sha256": "29b1553359d37a53c529b8a2b53ba646cca6b4b401ba7a9722e0e1f15510e676"} [citrulline-p2788888] Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase. (1989). https://pubmed.ncbi.nlm.nih.gov/2788888/
    Complete structured claim and evidence

  2. ASS1-deficient citrullinemia type I models showed greater pyrimidine synthesis and proliferation than citrin-deficient type II models, where aspartate delivery was restricted.

    Comparison of ASS1 deficiency and citrin deficiency → Pyrimidine synthesis in citrullinemia study models source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human disorder-derived observations and experimental disease/cancer comparisons.
    limitations
    Neither condition is simple low dietary aspartate; do not turn cellular proliferation measures into patient cancer-risk estimates.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Two defects affecting the same cycle can leave very different amounts of substrate for another pathway.
    primary_references
    Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 178–184

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human disorder-derived observations and experimental disease/cancer comparisons. · source_derived_draft · unverified_draft

    ## l-aspartate-ass1-citrin-difference Two defects affecting the same cycle can leave very different amounts of substrate for another pathway. ASS1-deficient citrullinemia type I models showed greater pyrimidine synthesis and proliferation than citrin-deficient type II models, where aspartate delivery was restricted. Model: Human disorder-derived observations and experimental disease/cancer comparisons. Limitations: Neither condition is simple low dietary aspartate; do not turn cellular proliferation measures into patient cancer-risk estimates. Evidence access: Primary abstract Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
    Complete structured claim and evidence

  3. Reduced ASS1 activity increased cytosolic aspartate availability and CAD-dependent pyrimidine synthesis in the studied cancer models.

    Reduced ASS1 activity in human tumor models → L-Aspartate source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human cancer-cell perturbations, metabolic analysis and disease-related comparisons.
    limitations
    The finding does not mean reducing nitrogen disposal is beneficial; it is a tumor-model mechanism.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Using less aspartate for arginine synthesis can leave more for nucleotide synthesis.
    primary_references
    Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 170–176

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell perturbations, metabolic analysis and disease-related comparisons. · source_derived_draft · unverified_draft

    ## l-aspartate-ass1-diversion Using less aspartate for arginine synthesis can leave more for nucleotide synthesis. Reduced ASS1 activity increased cytosolic aspartate availability and CAD-dependent pyrimidine synthesis in the studied cancer models. Model: Human cancer-cell perturbations, metabolic analysis and disease-related comparisons. Limitations: The finding does not mean reducing nitrogen disposal is beneficial; it is a tumor-model mechanism. Evidence access: Primary abstract Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
    Complete structured claim and evidence

  4. Adding pegargiminase to chemotherapy increased median survival from 7.7 to 9.3 months; death hazard ratio 0.71.

    Pegargiminase / ADI-PEG20 → Overall survival in nonepithelioid pleural mesothelioma source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    ATOMIC-Meso: 249 patients, nonepithelioid pleural mesothelioma; weekly 36.8 mg/m² plus pemetrexed/platinum.
    limitations
    Drug combination trial, not dietary restriction or a general cancer treatment.
    nutrient_topic
    L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
    plain_language
    Arginine depletion can have a therapeutic role in a specific tumor context.
    primary_references
    Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38358753/ · DOI 10.1001/jamaoncol.2023.6789

    L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 406–412

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · ATOMIC-Meso: 249 patients, nonepithelioid pleural mesothelioma; weekly 36.8 mg/m² plus pemetrexed/platinum. · source_derived_draft · unverified_draft

    ## arg-tumor-survival Arginine depletion can have a therapeutic role in a specific tumor context. Adding pegargiminase to chemotherapy increased median survival from 7.7 to 9.3 months; death hazard ratio 0.71. Model: ATOMIC-Meso: 249 patients, nonepithelioid pleural mesothelioma; weekly 36.8 mg/m² plus pemetrexed/platinum. Limitations: Drug combination trial, not dietary restriction or a general cancer treatment. Evidence access: Primary abstract Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38358753/ · DOI 10.1001/jamaoncol.2023.6789
    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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