Component

Coenzyme A synthase / COASY

Human bifunctional phosphopantetheine adenylyltransferase/dephospho-CoA kinase.

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. Human COASY phosphopantetheine adenylyltransferase activity used ATP and 4′-phosphopantetheine to form dephospho-CoA.

    Coenzyme A synthase / COASY → 4′-Phosphopantetheine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
    exposure
    Forward PPAT assays: 5–500 micromolar phosphopantetheine and 5 mM ATP; 0.15–0.3 micrograms/mL recombinant COASY.
    limitations
    Direct biochemical reaction, distinct from the final phosphorylation; does not establish efficient entry of an oral intermediate into human cells.
    nutrient_topic
    Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
    organism
    Homo sapiens
    plain_language
    COASY adds the adenosine-containing portion of CoA.
    primary_references
    [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 574–585

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft

    ### b5-bio-coasy-adenylylation Human COASY phosphopantetheine adenylyltransferase activity used ATP and 4′-phosphopantetheine to form dephospho-CoA. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: COASY adds the adenosine-containing portion of CoA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Direct biochemical reaction, distinct from the final phosphorylation; does not establish efficient entry of an oral intermediate into human cells. exposure: Forward PPAT assays: 5–500 micromolar phosphopantetheine and 5 mM ATP; 0.15–0.3 micrograms/mL recombinant COASY. cross_nutrient: false [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
    Complete structured claim and evidence

  2. Human COASY dephospho-CoA kinase activity phosphorylated dephospho-CoA to CoA using ATP; deleting the C-terminal domain retained PPAT but removed DPCK activity.

    Coenzyme A synthase / COASY → 3′-Dephospho-coenzyme A source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
    exposure
    DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis.
    limitations
    Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured.
    nutrient_topic
    Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
    organism
    Homo sapiens
    plain_language
    The final COASY reaction completes CoA.
    primary_references
    [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 587–598

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft

    ### b5-bio-coasy-phosphorylation Human COASY dephospho-CoA kinase activity phosphorylated dephospho-CoA to CoA using ATP; deleting the C-terminal domain retained PPAT but removed DPCK activity. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The final COASY reaction completes CoA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Recombinant enzyme and truncation studies define two distinct COASY activities; no whole-body nutritional threshold is measured. exposure: DPCK assay: 5–100 micromolar dephospho-CoA, 1 mM ATP; coupled ADP readout and direct HPLC product analysis. cross_nutrient: false [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro.

    4-Phosphopantothenate → Coenzyme A source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested.
    evidence
    [{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Reconstituted human enzyme pathway.
    limitations
    Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction.
    nutrient
    Thiamine (vitamin B1) · Thiamine (vitamin B1)
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step.
    primary_references
    [daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
    tissue_or_cell_type
    Purified recombinant enzymes

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 731–743

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human enzyme pathway. · source_derived_draft · unverified_draft

    ### b1-coa-b5-downstream-biosynthesis Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzymes experimental_model: Reconstituted human enzyme pathway. limitations: Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction. evidence: [{"paper_key": "daugherty-2002-coa", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested. nutrient: Thiamine (vitamin B1) [daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
    Complete structured claim and evidence

  2. Free-CoA levels in fibroblasts from the two COASY cases were not significantly different from the control in the reported HPLC analysis.

    Human pathogenic COASY genotypes in the Dusi 2014 cases → Free coenzyme A in primary fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies
    exposure
    Two affected individuals versus one healthy-control fibroblast line; four independent experiments shown in Fig. 6.
    limitations
    Small cell-line comparison and an absence of statistical significance, not proof of equal CoA in all compartments or tissues. Acetyl-CoA was significantly lower in one case; total-CoA trends and free-CoA results must not be conflated.
    nutrient_topic
    Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
    organism
    Homo sapiens
    plain_language
    A severe enzyme defect did not imply an absent whole-cell free-CoA pool in these fibroblasts.
    primary_references
    [b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008
    tissue_or_cell_type
    Human primary skin fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 743–754

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies · source_derived_draft · unverified_draft

    ### b5-bio-coasy-fibroblast-free-coa Free-CoA levels in fibroblasts from the two COASY cases were not significantly different from the control in the reported HPLC analysis. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A severe enzyme defect did not imply an absent whole-cell free-CoA pool in these fibroblasts. organism: Homo sapiens tissue_or_cell_type: Human primary skin fibroblasts experimental_model: Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies limitations: Small cell-line comparison and an absence of statistical significance, not proof of equal CoA in all compartments or tissues. Acetyl-CoA was significantly lower in one case; total-CoA trends and free-CoA results must not be conflated. exposure: Two affected individuals versus one healthy-control fibroblast line; four independent experiments shown in Fig. 6. cross_nutrient: false [b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008
    Complete structured claim and evidence

  3. The recombinant COASY DPCK domain carrying p.Arg499Cys did not produce a detectable CoA HPLC peak, whereas wild-type DPCK converted dephospho-CoA to CoA.

    Human COASY p.Arg499Cys protein → 3′-Dephospho-coenzyme A source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies
    exposure
    HPLC assays with 1 microgram recombinant wild-type or p.Arg499Cys DPCK protein, ATP and dephospho-CoA; substrate concentrations not extracted.
    limitations
    Loss of detectable isolated-domain activity does not mean that every patient cell has no CoA. Wild-type and variant domains were recombinantly produced in bacteria.
    nutrient_topic
    Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
    organism
    Homo sapiens
    plain_language
    This COASY variant disabled the final reaction in the isolated-enzyme test.
    primary_references
    [b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 730–741

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies · source_derived_draft · unverified_draft

    ### b5-bio-coasy-r499c-activity The recombinant COASY DPCK domain carrying p.Arg499Cys did not produce a detectable CoA HPLC peak, whereas wild-type DPCK converted dephospho-CoA to CoA. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: This COASY variant disabled the final reaction in the isolated-enzyme test. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Two unrelated human NBIA cases, primary fibroblasts, recombinant wild-type and variant COASY DPCK domains and yeast studies limitations: Loss of detectable isolated-domain activity does not mean that every patient cell has no CoA. Wild-type and variant domains were recombinantly produced in bacteria. exposure: HPLC assays with 1 microgram recombinant wild-type or p.Arg499Cys DPCK protein, ATP and dephospho-CoA; substrate concentrations not extracted. cross_nutrient: false [b5-bio-coasy2014] Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation. (2014). https://pubmed.ncbi.nlm.nih.gov/24360804/ DOI: 10.1016/j.ajhg.2013.11.008
    Complete structured claim and evidence

  4. The 2015 salvage paper interpreted its experiments as passive membrane entry of extracellular 4′-phosphopantetheine before conversion back to CoA.

    4′-Phosphopantetheine → Cellular entry of extracellular 4′-phosphopantetheine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments
    exposure
    Extracellular 4′-phosphopantetheine/CoA exposure; concentrations not extracted.
    limitations
    Author mechanistic interpretation preserved as a hypothesis. Abstract-only extraction cannot exclude extracellular dephosphorylation/rephosphorylation or establish passive uptake in every tissue, serum stability, or blood–brain-barrier delivery.
    nutrient_topic
    Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
    organism
    Eukaryotic cell/organism models; assay-level species not specified in abstract
    plain_language
    The authors proposed direct entry of the intermediate; the transport route remains a separate question from downstream enzyme activity.
    primary_references
    [b5-bio-salvage2015] Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26322826/ DOI: 10.1038/nchembio.1906
    tissue_or_cell_type
    Cell membrane and intracellular CoA synthesis

    Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 769–780

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments · source_derived_draft · unverified_draft

    ### b5-bio-phosphopantetheine-entry-proposal The 2015 salvage paper interpreted its experiments as passive membrane entry of extracellular 4′-phosphopantetheine before conversion back to CoA. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The authors proposed direct entry of the intermediate; the transport route remains a separate question from downstream enzyme activity. organism: Eukaryotic cell/organism models; assay-level species not specified in abstract tissue_or_cell_type: Cell membrane and intracellular CoA synthesis experimental_model: Biochemical extracellular-CoA hydrolysis and eukaryotic cell/organism salvage experiments limitations: Author mechanistic interpretation preserved as a hypothesis. Abstract-only extraction cannot exclude extracellular dephosphorylation/rephosphorylation or establish passive uptake in every tissue, serum stability, or blood–brain-barrier delivery. exposure: Extracellular 4′-phosphopantetheine/CoA exposure; concentrations not extracted. cross_nutrient: false [b5-bio-salvage2015] Extracellular 4'-phosphopantetheine is a source for intracellular coenzyme A synthesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26322826/ DOI: 10.1038/nchembio.1906
    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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