Component

Human CAD multifunctional pyrimidine synthesis enzyme

Context-specific entity; species, compartment and exposure are stated on each 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. Purified human CAD aspartate-transcarbamylase domain converted carbamoyl phosphate and aspartate to carbamoyl-aspartate in an initial-rate assay.

    Human CAD multifunctional pyrimidine synthesis enzyme → N-Carbamoyl-L-aspartate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Recombinant human CAD ATCase domain fused to MBP; biochemical assay.
    limitations
    Isolated-domain kinetics are not whole-cell nucleotide flux.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Aspartate becomes part of the precursor used to build pyrimidine bases.
    primary_references
    Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 146–152

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human CAD ATCase domain fused to MBP; biochemical assay. · source_derived_draft · unverified_draft

    ## l-aspartate-cad-aspartate-reaction Aspartate becomes part of the precursor used to build pyrimidine bases. Purified human CAD aspartate-transcarbamylase domain converted carbamoyl phosphate and aspartate to carbamoyl-aspartate in an initial-rate assay. Model: Recombinant human CAD ATCase domain fused to MBP; biochemical assay. Limitations: Isolated-domain kinetics are not whole-cell nucleotide flux. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
    Complete structured claim and evidence

What acts on it

  1. S6K1 directly phosphorylated CAD at Ser1859, connecting mTORC1 signaling to increased de novo pyrimidine synthesis.

    Human p70 S6 kinase / RPS6KB1 → Human CAD multifunctional pyrimidine synthesis enzyme source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing.
    limitations
    This is a signaling dependency, not evidence that a specific nutrient supplement necessarily increases CAD activity.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Growth signals can accelerate use of aspartate for nucleotide production.
    primary_references
    Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 154–160

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing. · source_derived_draft · unverified_draft

    ## l-aspartate-cad-s6k1 Growth signals can accelerate use of aspartate for nucleotide production. S6K1 directly phosphorylated CAD at Ser1859, connecting mTORC1 signaling to increased de novo pyrimidine synthesis. Model: Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing. Limitations: This is a signaling dependency, not evidence that a specific nutrient supplement necessarily increases CAD activity. Evidence access: Primary full text Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792
    Complete structured claim and evidence

  2. Succinate competitively inhibited aspartate utilization by the purified human CAD ATCase domain.

    Succinate → Human CAD multifunctional pyrimidine synthesis enzyme source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Recombinant human ATCase kinetic experiments with succinate and substrate titration.
    limitations
    This is not proof that ordinary dietary succinate or aspartate concentrations cause the same inhibition in a person.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    An accumulated carbon-cycle metabolite competes with aspartate at a nucleotide-making enzyme.
    primary_references
    Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 210–216

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human ATCase kinetic experiments with succinate and substrate titration. · source_derived_draft · unverified_draft

    ## l-aspartate-succinate-atcase An accumulated carbon-cycle metabolite competes with aspartate at a nucleotide-making enzyme. Succinate competitively inhibited aspartate utilization by the purified human CAD ATCase domain. Model: Recombinant human ATCase kinetic experiments with succinate and substrate titration. Limitations: This is not proof that ordinary dietary succinate or aspartate concentrations cause the same inhibition in a person. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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

  2. 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

  3. Bovine albumin supplementation restored aspartate and pyrimidine-related metabolites and partly rescued hypoxic growth in the tested KRAS-mutant human PDAC cultures.

    Bovine serum albumin → Aspartate supplied by protein scavenging in human PDAC cells source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments.
    limitations
    This is an extracellular protein-scavenging mechanism, not evidence of direct intact dietary protein delivery to a tumor.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    Cells can obtain amino acids by digesting extracellular protein.
    primary_references
    Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 258–264

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments. · source_derived_draft · unverified_draft

    ## l-aspartate-protein-scavenging-rescue Cells can obtain amino acids by digesting extracellular protein. Bovine albumin supplementation restored aspartate and pyrimidine-related metabolites and partly rescued hypoxic growth in the tested KRAS-mutant human PDAC cultures. Model: Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments. Limitations: This is an extracellular protein-scavenging mechanism, not evidence of direct intact dietary protein delivery to a tumor. Evidence access: Primary full text Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
    Complete structured claim and evidence

  4. SDH loss increased succinate, impaired aspartate entry into pyrimidine synthesis and produced nucleotide insufficiency with replication stress and increased ATR-inhibitor sensitivity.

    SDH inhibition or loss in human cell models → Pyrimidine production after human-cell SDH impairment 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 genetic/pharmacological SDH perturbations; nucleotide and replication readouts.
    limitations
    Not a clinical treatment recommendation or proof that extra aspartate universally overcomes the competitive block.
    nutrient_topic
    L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
    plain_language
    The effect propagated from metabolism into DNA replication control.
    primary_references
    Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 218–224

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell genetic/pharmacological SDH perturbations; nucleotide and replication readouts. · source_derived_draft · unverified_draft

    ## l-aspartate-sdh-pyrimidine-stress The effect propagated from metabolism into DNA replication control. SDH loss increased succinate, impaired aspartate entry into pyrimidine synthesis and produced nucleotide insufficiency with replication stress and increased ATR-inhibitor sensitivity. Model: Human cell genetic/pharmacological SDH perturbations; nucleotide and replication readouts. Limitations: Not a clinical treatment recommendation or proof that extra aspartate universally overcomes the competitive block. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
    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