Component

Human holocarboxylase synthetase / HLCS

Human holocarboxylase synthetase / HLCS. Species, exposure and limitations are retained in each linked claim.

15 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. HLCS biotinylation of the human ACACA acceptor fragment was relatively slow and depended hyperbolically on fragment concentration.

    Human holocarboxylase synthetase / HLCS → Human acetyl-CoA carboxylase 1 / ACACA source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"}
    experimental_model
    Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases
    exposure
    Stopped-flow and quench-flow transfer kinetics
    limitations
    Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    The two acetyl-CoA carboxylases showed different attachment kinetics from the mitochondrial carboxylase fragments.
    primary_references
    [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    tissue_or_cell_type
    Purified HLCS and acceptor fragments

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 429–440

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases · source_derived_draft · unverified_draft

    ### b7-hlcs-acaca-acceptor HLCS biotinylation of the human ACACA acceptor fragment was relatively slow and depended hyperbolically on fragment concentration. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two acetyl-CoA carboxylases showed different attachment kinetics from the mitochondrial carboxylase fragments. organism: Homo sapiens tissue_or_cell_type: Purified HLCS and acceptor fragments experimental_model: Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases limitations: Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans. exposure: Stopped-flow and quench-flow transfer kinetics evidence_span: {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"} [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    Complete structured claim and evidence

  2. HLCS biotinylation of the human ACACB acceptor fragment was relatively slow and depended hyperbolically on fragment concentration.

    Human holocarboxylase synthetase / HLCS → Human acetyl-CoA carboxylase 2 / ACACB source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"}
    experimental_model
    Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases
    exposure
    Stopped-flow and quench-flow transfer kinetics
    limitations
    Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    The two acetyl-CoA carboxylases showed different attachment kinetics from the mitochondrial carboxylase fragments.
    primary_references
    [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    tissue_or_cell_type
    Purified HLCS and acceptor fragments

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 442–453

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases · source_derived_draft · unverified_draft

    ### b7-hlcs-acacb-acceptor HLCS biotinylation of the human ACACB acceptor fragment was relatively slow and depended hyperbolically on fragment concentration. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two acetyl-CoA carboxylases showed different attachment kinetics from the mitochondrial carboxylase fragments. organism: Homo sapiens tissue_or_cell_type: Purified HLCS and acceptor fragments experimental_model: Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases limitations: Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans. exposure: Stopped-flow and quench-flow transfer kinetics evidence_span: {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"} [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    Complete structured claim and evidence

  3. HLCS activates biotin with ATP to form enzyme-bound biotinyl-5-prime-AMP before transferring biotin to a carboxylase acceptor.

    Human holocarboxylase synthetase / HLCS → Biotinyl-5-prime-AMP source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/19740736.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d785655901465bc9798378986d954b87111e3bd73d6877d9d60ae3d95cac0a37", "start_char": 2587, "end_char": 3080, "text_sha256": "fa0ec838311a45e8ccebf38a73e340a46417eae6bc300064c1165a4a0b711889"}
    experimental_model
    Purified full-length and residue-58 human HLCS isoforms expressed in E. coli
    exposure
    Biotin/ATP activation and single-turnover biotin transfer
    limitations
    Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    Biotin must first be activated before it can be attached to an enzyme.
    primary_references
    [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
    tissue_or_cell_type
    Purified proteins and minimal biotin-accepting substrate

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 351–362

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length and residue-58 human HLCS isoforms expressed in E. coli · source_derived_draft · unverified_draft

    ### b7-hlcs-adenylation HLCS activates biotin with ATP to form enzyme-bound biotinyl-5-prime-AMP before transferring biotin to a carboxylase acceptor. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin must first be activated before it can be attached to an enzyme. organism: Homo sapiens tissue_or_cell_type: Purified proteins and minimal biotin-accepting substrate experimental_model: Purified full-length and residue-58 human HLCS isoforms expressed in E. coli limitations: Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species. exposure: Biotin/ATP activation and single-turnover biotin transfer evidence_span: {"source_cache": "artifacts/biotin-research/19740736.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d785655901465bc9798378986d954b87111e3bd73d6877d9d60ae3d95cac0a37", "start_char": 2587, "end_char": 3080, "text_sha256": "fa0ec838311a45e8ccebf38a73e340a46417eae6bc300064c1165a4a0b711889"} [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
    Complete structured claim and evidence

  4. Full-length human HLCS associated with the minimal biotin acceptor about twice as fast as the residue-58 isoform in pre-steady-state transfer measurements.

    Human holocarboxylase synthetase / HLCS → Human HLCS beginning at residue 58 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/19740736.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "27724d2b900152fade1d3be186d350c2b1862e5281355990f4720236798248ed", "start_char": 0, "end_char": 1259, "text_sha256": "27724d2b900152fade1d3be186d350c2b1862e5281355990f4720236798248ed"}
    experimental_model
    Purified full-length and residue-58 human HLCS isoforms expressed in E. coli
    exposure
    Biotin/ATP activation and single-turnover biotin transfer
    limitations
    Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    Two HLCS forms recognize an enzyme attachment site at different rates.
    primary_references
    [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
    tissue_or_cell_type
    Purified proteins and minimal biotin-accepting substrate

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 377–388

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length and residue-58 human HLCS isoforms expressed in E. coli · source_derived_draft · unverified_draft

    ### b7-hlcs-isoform-kinetics Full-length human HLCS associated with the minimal biotin acceptor about twice as fast as the residue-58 isoform in pre-steady-state transfer measurements. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two HLCS forms recognize an enzyme attachment site at different rates. organism: Homo sapiens tissue_or_cell_type: Purified proteins and minimal biotin-accepting substrate experimental_model: Purified full-length and residue-58 human HLCS isoforms expressed in E. coli limitations: Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species. exposure: Biotin/ATP activation and single-turnover biotin transfer evidence_span: {"source_cache": "artifacts/biotin-research/19740736.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "27724d2b900152fade1d3be186d350c2b1862e5281355990f4720236798248ed", "start_char": 0, "end_char": 1259, "text_sha256": "27724d2b900152fade1d3be186d350c2b1862e5281355990f4720236798248ed"} [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
    Complete structured claim and evidence

  5. HLCS transfers the activated biotin moiety to the epsilon-amino group of a specific lysine in a carboxylase biotin-acceptor domain.

    Human holocarboxylase synthetase / HLCS → Protein-bound lysine residue source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/19740736.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d785655901465bc9798378986d954b87111e3bd73d6877d9d60ae3d95cac0a37", "start_char": 2587, "end_char": 3080, "text_sha256": "fa0ec838311a45e8ccebf38a73e340a46417eae6bc300064c1165a4a0b711889"}
    experimental_model
    Purified full-length and residue-58 human HLCS isoforms expressed in E. coli
    exposure
    Biotin/ATP activation and single-turnover biotin transfer
    limitations
    Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    Biotin becomes a tethered part of the enzyme; free lysine and enzyme-bound lysine are different entities.
    primary_references
    [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
    tissue_or_cell_type
    Purified proteins and minimal biotin-accepting substrate

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 364–375

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified full-length and residue-58 human HLCS isoforms expressed in E. coli · source_derived_draft · unverified_draft

    ### b7-hlcs-lysine-transfer HLCS transfers the activated biotin moiety to the epsilon-amino group of a specific lysine in a carboxylase biotin-acceptor domain. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin becomes a tethered part of the enzyme; free lysine and enzyme-bound lysine are different entities. organism: Homo sapiens tissue_or_cell_type: Purified proteins and minimal biotin-accepting substrate experimental_model: Purified full-length and residue-58 human HLCS isoforms expressed in E. coli limitations: Minimal-substrate kinetics do not prove a universal tissue allocation hierarchy; expression host is not the protein species. exposure: Biotin/ATP activation and single-turnover biotin transfer evidence_span: {"source_cache": "artifacts/biotin-research/19740736.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d785655901465bc9798378986d954b87111e3bd73d6877d9d60ae3d95cac0a37", "start_char": 2587, "end_char": 3080, "text_sha256": "fa0ec838311a45e8ccebf38a73e340a46417eae6bc300064c1165a4a0b711889"} [b7-p19740736] Distinct amino termini of two human HCS isoforms influence biotin acceptor substrate recognition. (2009). https://pubmed.ncbi.nlm.nih.gov/19740736/ DOI: 10.1074/jbc.m109.046201
    Complete structured claim and evidence

  6. HLCS rapidly biotinylated the biotin-acceptor fragment of human MCCC1, with transfer limited by enzyme-substrate association.

    Human holocarboxylase synthetase / HLCS → Human methylcrotonyl-CoA carboxylase alpha subunit / MCCC1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"}
    experimental_model
    Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases
    exposure
    Stopped-flow and quench-flow transfer kinetics
    limitations
    Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    This mitochondrial enzyme has a biotin attachment domain recognized by HLCS.
    primary_references
    [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    tissue_or_cell_type
    Purified HLCS and acceptor fragments

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 416–427

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases · source_derived_draft · unverified_draft

    ### b7-hlcs-mcc-acceptor HLCS rapidly biotinylated the biotin-acceptor fragment of human MCCC1, with transfer limited by enzyme-substrate association. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mitochondrial enzyme has a biotin attachment domain recognized by HLCS. organism: Homo sapiens tissue_or_cell_type: Purified HLCS and acceptor fragments experimental_model: Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases limitations: Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans. exposure: Stopped-flow and quench-flow transfer kinetics evidence_span: {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"} [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    Complete structured claim and evidence

  7. HLCS rapidly biotinylated the biotin-acceptor fragment of human PC, with transfer limited by enzyme-substrate association.

    Human holocarboxylase synthetase / HLCS → Human pyruvate carboxylase / PC source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"}
    experimental_model
    Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases
    exposure
    Stopped-flow and quench-flow transfer kinetics
    limitations
    Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    This mitochondrial enzyme has a biotin attachment domain recognized by HLCS.
    primary_references
    [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    tissue_or_cell_type
    Purified HLCS and acceptor fragments

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 390–401

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases · source_derived_draft · unverified_draft

    ### b7-hlcs-pc-acceptor HLCS rapidly biotinylated the biotin-acceptor fragment of human PC, with transfer limited by enzyme-substrate association. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mitochondrial enzyme has a biotin attachment domain recognized by HLCS. organism: Homo sapiens tissue_or_cell_type: Purified HLCS and acceptor fragments experimental_model: Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases limitations: Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans. exposure: Stopped-flow and quench-flow transfer kinetics evidence_span: {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"} [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    Complete structured claim and evidence

  8. HLCS rapidly biotinylated the biotin-acceptor fragment of human PCCA, with transfer limited by enzyme-substrate association.

    Human holocarboxylase synthetase / HLCS → Human propionyl-CoA carboxylase alpha subunit / PCCA source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"}
    experimental_model
    Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases
    exposure
    Stopped-flow and quench-flow transfer kinetics
    limitations
    Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    This mitochondrial enzyme has a biotin attachment domain recognized by HLCS.
    primary_references
    [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    tissue_or_cell_type
    Purified HLCS and acceptor fragments

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 403–414

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases · source_derived_draft · unverified_draft

    ### b7-hlcs-pcc-acceptor HLCS rapidly biotinylated the biotin-acceptor fragment of human PCCA, with transfer limited by enzyme-substrate association. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mitochondrial enzyme has a biotin attachment domain recognized by HLCS. organism: Homo sapiens tissue_or_cell_type: Purified HLCS and acceptor fragments experimental_model: Single-turnover biotin transfer to minimal BCCP fragments from all five human carboxylases limitations: Fragment kinetics support differential recognition, not a universal nutrient-deficiency survival order in humans. exposure: Stopped-flow and quench-flow transfer kinetics evidence_span: {"source_cache": "artifacts/biotin-research/22123817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233", "start_char": 0, "end_char": 1502, "text_sha256": "559afe20b6f8601a2d055d42fb121c89eaf1ece76afaa5cc0817c20787893233"} [b7-p22123817] Selectivity in post-translational biotin addition to five human carboxylases. (2012). https://pubmed.ncbi.nlm.nih.gov/22123817/ DOI: 10.1074/jbc.m111.275982
    Complete structured claim and evidence

  9. Lower residual HLCS Vmax correlated with poorer PCC and clinical responses to biotin in the studied variants and patients; non-Km variants could also respond.

    Human holocarboxylase synthetase / HLCS → Biochemical response to biotin in HLCS deficiency source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"}
    experimental_model
    Kinetics of seven human HLCS variants, patient cells and clinical response comparison
    exposure
    Genetic variants and biotin supplementation
    limitations
    Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    An enzyme with very little remaining capacity may respond less, even when more biotin is supplied.
    primary_references
    [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004
    tissue_or_cell_type
    Purified variants and cultured patient cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 520–531

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics of seven human HLCS variants, patient cells and clinical response comparison · source_derived_draft · unverified_draft

    ### b7-hlcs-vmax-response Lower residual HLCS Vmax correlated with poorer PCC and clinical responses to biotin in the studied variants and patients; non-Km variants could also respond. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme with very little remaining capacity may respond less, even when more biotin is supplied. organism: Homo sapiens tissue_or_cell_type: Purified variants and cultured patient cells experimental_model: Kinetics of seven human HLCS variants, patient cells and clinical response comparison limitations: Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency. exposure: Genetic variants and biotin supplementation evidence_span: {"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"} [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004
    Complete structured claim and evidence

What acts on it

  1. Resveratrol inhibited recombinant human HLCS-dependent biotinylation in vitro, with reported IC50 approximately 3.70 micromolar.

    Resveratrol → Human holocarboxylase synthetase / HLCS source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Gel-based biotin-acceptor assay and dose response.
    limitations
    Human biotin depletion or failure of biotin repletion was not demonstrated.
    nutrient_topic
    Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
    plain_language
    A direct laboratory connection to biotin activation is searchable.
    primary_references
    Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004

    Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 342–348

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Gel-based biotin-acceptor assay and dose response. · source_derived_draft · unverified_draft

    ## resveratrol-hlcs-inhibition A direct laboratory connection to biotin activation is searchable. Resveratrol inhibited recombinant human HLCS-dependent biotinylation in vitro, with reported IC50 approximately 3.70 micromolar. Model: Gel-based biotin-acceptor assay and dose response. Limitations: Human biotin depletion or failure of biotin repletion was not demonstrated. Evidence access: Primary full text Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Biotinidase impairment reduced carboxylase biotinylation and disrupted HLCS and carboxylase expression in the studied human cell model.

    Human biotinidase / BTD → Human HLCS expression source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/biotin-research/18845537.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "86a05dc5e8386be649b3f876891503e507217c8f2dd11d9637c67e76effda407", "start_char": 0, "end_char": 1458, "text_sha256": "86a05dc5e8386be649b3f876891503e507217c8f2dd11d9637c67e76effda407"}
    experimental_model
    Biotinidase-deficient human cell model compared with control cells
    exposure
    Biotin recycling impairment and biotin repletion experiments
    limitations
    The proposed brain-protective tissue-allocation mechanism remains an author model, not an established human ranking.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    Loss of recycling can affect both cofactor attachment and expression of the attachment machinery.
    primary_references
    [b7-p18845537] Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency. (2008). https://pubmed.ncbi.nlm.nih.gov/18845537/ DOI: 10.1074/jbc.m806985200
    tissue_or_cell_type
    Cultured patient-derived cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 481–492

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biotinidase-deficient human cell model compared with control cells · source_derived_draft · unverified_draft

    ### b7-btd-expression Biotinidase impairment reduced carboxylase biotinylation and disrupted HLCS and carboxylase expression in the studied human cell model. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of recycling can affect both cofactor attachment and expression of the attachment machinery. organism: Homo sapiens tissue_or_cell_type: Cultured patient-derived cells experimental_model: Biotinidase-deficient human cell model compared with control cells limitations: The proposed brain-protective tissue-allocation mechanism remains an author model, not an established human ranking. exposure: Biotin recycling impairment and biotin repletion experiments evidence_span: {"source_cache": "artifacts/biotin-research/18845537.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "86a05dc5e8386be649b3f876891503e507217c8f2dd11d9637c67e76effda407", "start_char": 0, "end_char": 1458, "text_sha256": "86a05dc5e8386be649b3f876891503e507217c8f2dd11d9637c67e76effda407"} [b7-p18845537] Impaired biotinidase activity disrupts holocarboxylase synthetase expression in late onset multiple carboxylase deficiency. (2008). https://pubmed.ncbi.nlm.nih.gov/18845537/ DOI: 10.1074/jbc.m806985200
    Complete structured claim and evidence

  2. The 2011 study reported natural biotinylation of less than 0.001% of human H3/H4 and argued for rare modification rather than a universal assay artifact.

    Biotin → Detection of biotin on human histones source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/biotin-research/21930408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "51af2341c7be0cb58c57e09784ebb8daabdd98cc93f04be52bb7b04b496e0b91", "start_char": 0, "end_char": 1318, "text_sha256": "51af2341c7be0cb58c57e09784ebb8daabdd98cc93f04be52bb7b04b496e0b91"}
    experimental_model
    Multiple antibody, radiotracer and cell-line comparisons of human histone biotinylation
    exposure
    Assay comparisons responding to artifact criticism
    limitations
    Authors estimated extremely low abundance and proposed HLCS chromatin scaffolding as a working model; nutritional epigenetic benefit was not demonstrated.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    Later work defended a very rare mark while questioning whether that tiny amount explains biological effects.
    primary_references
    [b7-p21930408] Biotinylation is a natural, albeit rare, modification of human histones. (2011). https://pubmed.ncbi.nlm.nih.gov/21930408/ DOI: 10.1016/j.ymgme.2011.08.030
    tissue_or_cell_type
    Human histones H3/H4 in cultured cells

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1183–1194

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multiple antibody, radiotracer and cell-line comparisons of human histone biotinylation · source_derived_draft · unverified_draft

    ### b7-histone-rare-report The 2011 study reported natural biotinylation of less than 0.001% of human H3/H4 and argued for rare modification rather than a universal assay artifact. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Later work defended a very rare mark while questioning whether that tiny amount explains biological effects. organism: Homo sapiens tissue_or_cell_type: Human histones H3/H4 in cultured cells experimental_model: Multiple antibody, radiotracer and cell-line comparisons of human histone biotinylation limitations: Authors estimated extremely low abundance and proposed HLCS chromatin scaffolding as a working model; nutritional epigenetic benefit was not demonstrated. exposure: Assay comparisons responding to artifact criticism evidence_span: {"source_cache": "artifacts/biotin-research/21930408.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "51af2341c7be0cb58c57e09784ebb8daabdd98cc93f04be52bb7b04b496e0b91", "start_char": 0, "end_char": 1318, "text_sha256": "51af2341c7be0cb58c57e09784ebb8daabdd98cc93f04be52bb7b04b496e0b91"} [b7-p21930408] Biotinylation is a natural, albeit rare, modification of human histones. (2011). https://pubmed.ncbi.nlm.nih.gov/21930408/ DOI: 10.1016/j.ymgme.2011.08.030
    Complete structured claim and evidence

  3. The human HLCS Gly581Ser variant had a biotin Km approximately 45 times the wild-type value.

    Human HLCS Gly581Ser variant → Biotin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"}
    experimental_model
    Kinetics of seven human HLCS variants, patient cells and clinical response comparison
    exposure
    Genetic variants and biotin supplementation
    limitations
    Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    This variant required much more biotin to reach the same fraction of its own maximum rate.
    primary_references
    [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004
    tissue_or_cell_type
    Purified variants and cultured patient cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 494–505

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics of seven human HLCS variants, patient cells and clinical response comparison · source_derived_draft · unverified_draft

    ### b7-hlcs-g581s The human HLCS Gly581Ser variant had a biotin Km approximately 45 times the wild-type value. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This variant required much more biotin to reach the same fraction of its own maximum rate. organism: Homo sapiens tissue_or_cell_type: Purified variants and cultured patient cells experimental_model: Kinetics of seven human HLCS variants, patient cells and clinical response comparison limitations: Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency. exposure: Genetic variants and biotin supplementation evidence_span: {"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"} [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004
    Complete structured claim and evidence

  4. The human HLCS Thr610-deletion variant had a biotin Km approximately three times the wild-type value.

    Human HLCS Thr610 deletion variant → Biotin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"}
    experimental_model
    Kinetics of seven human HLCS variants, patient cells and clinical response comparison
    exposure
    Genetic variants and biotin supplementation
    limitations
    Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency.
    nutrient_topic
    Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
    organism
    Homo sapiens
    plain_language
    Different HLCS variants impair biotin use by different amounts.
    primary_references
    [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004
    tissue_or_cell_type
    Purified variants and cultured patient cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 507–518

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics of seven human HLCS variants, patient cells and clinical response comparison · source_derived_draft · unverified_draft

    ### b7-hlcs-t610 The human HLCS Thr610-deletion variant had a biotin Km approximately three times the wild-type value. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different HLCS variants impair biotin use by different amounts. organism: Homo sapiens tissue_or_cell_type: Purified variants and cultured patient cells experimental_model: Kinetics of seven human HLCS variants, patient cells and clinical response comparison limitations: Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency. exposure: Genetic variants and biotin supplementation evidence_span: {"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"} [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004
    Complete structured claim and evidence

  5. In the human HLCS assay, inhibitory potency ranked piceatannol above resveratrol above piceid.

    Piceatannol → Piceid / polydatin source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Purified-compound enzyme comparison.
    limitations
    Does not mean all are circulating resveratrol metabolites under a given regimen.
    nutrient_topic
    Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
    plain_language
    Related compounds cannot be assigned identical potency.
    primary_references
    Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004

    Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 350–356

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-compound enzyme comparison. · source_derived_draft · unverified_draft

    ## resveratrol-hlcs-forms Related compounds cannot be assigned identical potency. In the human HLCS assay, inhibitory potency ranked piceatannol above resveratrol above piceid. Model: Purified-compound enzyme comparison. Limitations: Does not mean all are circulating resveratrol metabolites under a given regimen. Evidence access: Primary full text Resveratrol compounds inhibit human holocarboxylase synthetase and cause a lean phenotype in Drosophila melanogaster. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26303405/ · DOI 10.1016/j.jnutbio.2015.07.004
    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