Component

Human glycine-cleavage H-protein / GCSH

Human glycine-cleavage H-protein / GCSH

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 acts on it

  1. The lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain.

    Protein-bound oxidized lipoyl-lysine → Human glycine-cleavage H-protein / GCSH source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"}
    experimental_model
    X-ray structures of catalytic stages with human lipoyl synthase
    exposure
    Structural trapping of sulfur-insertion intermediates
    limitations
    Structural snapshots establish reaction intermediates, not clinical nutrient requirements.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human recombinant proteins
    plain_language
    The enzyme uses a tethered cofactor; free supplement molecules are a different pool.
    primary_references
    [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
    tissue_or_cell_type
    LIAS and H-protein substrate

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 247–258

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of catalytic stages with human lipoyl synthase · source_derived_draft · unverified_draft

    ### ala-lipoyl-lysine-anchor The lipoyl cofactor is attached through an amide linkage to a conserved carrier-protein lysine side chain. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme uses a tethered cofactor; free supplement molecules are a different pool. organism: Human recombinant proteins tissue_or_cell_type: LIAS and H-protein substrate experimental_model: X-ray structures of catalytic stages with human lipoyl synthase limitations: Structural snapshots establish reaction intermediates, not clinical nutrient requirements. exposure: Structural trapping of sulfur-insertion intermediates evidence_span: {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"} [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein.

    Human aminomethyltransferase / glycine-cleavage T-protein → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry.
    experimental_model
    Purified human AMT structures and mutational analyses
    limitations
    AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux.
    nutrient_topic
    Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
    organism
    Homo sapiens
    plain_language
    Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step.
    primary_references
    [b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 682–692

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human AMT structures and mutational analyses · source_derived_draft · unverified_draft

    ### b6-met-amt-onecarbon Human AMT transfers the aminomethyl-lipoyl intermediate's carbon to tetrahydrofolate, yielding 5,10-methylene-THF, ammonia and reduced H-protein. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glycine cleavage connects its B6-dependent first step to a separate folate-dependent step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human AMT structures and mutational analyses limitations: AMT is the directly examined human enzyme; this study did not test dietary B6 depletion or the entire pathway flux. cross_nutrient: B6-dependent GLDC precedes lipoyl-carrier transfer and folate-dependent AMT chemistry. [b6-amt-2005] Crystal structure of human T-protein of glycine cleavage system at 2.0 A resolution and its implication for understanding non-ketotic hyperglycinemia. (2005). https://pubmed.ncbi.nlm.nih.gov/16051266/ DOI: 10.1016/j.jmb.2005.06.056
    Complete structured claim and evidence

  2. GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine.

    Human mitochondrial glutaredoxin 5 / GLRX5 → Glycine accumulation in lipoylation disorders source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"}
    experimental_model
    Variant nonketotic hyperglycinemia cohort and cell complementation
    exposure
    LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells
    limitations
    Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human
    plain_language
    A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves.
    primary_references
    [ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
    tissue_or_cell_type
    Eight genetically explained patients within an eleven-person group
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 533–544

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Variant nonketotic hyperglycinemia cohort and cell complementation · source_derived_draft · unverified_draft

    ### ala-glrx5-glycine-failure GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves. organism: Human tissue_or_cell_type: Eight genetically explained patients within an eleven-person group experimental_model: Variant nonketotic hyperglycinemia cohort and cell complementation limitations: Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders. exposure: LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells evidence_span: {"source_cache": "artifacts/ala-research/24334290.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2", "start_char": 0, "end_char": 2342, "text_sha256": "2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2"} [ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328
    Complete structured claim and evidence

  3. Crystallography captured LIAS cross-linked to its H-protein substrate through a 6-mercaptooctanoyl ligand at a [3Fe-4S] cluster.

    Lipoic acid synthetase / LIAS → LIAS-GCSH 6-mercaptooctanoyl [3Fe-4S] intermediate source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"}
    experimental_model
    X-ray structures of catalytic stages with human lipoyl synthase
    exposure
    Structural trapping of sulfur-insertion intermediates
    limitations
    Structural snapshots establish reaction intermediates, not clinical nutrient requirements.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human recombinant proteins
    plain_language
    One sulfur-insertion intermediate temporarily links the enzyme, its iron-sulfur cluster and its substrate.
    primary_references
    [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
    tissue_or_cell_type
    LIAS and H-protein substrate

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 273–284

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures of catalytic stages with human lipoyl synthase · source_derived_draft · unverified_draft

    ### ala-lias-trapped-intermediate Crystallography captured LIAS cross-linked to its H-protein substrate through a 6-mercaptooctanoyl ligand at a [3Fe-4S] cluster. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: One sulfur-insertion intermediate temporarily links the enzyme, its iron-sulfur cluster and its substrate. organism: Human recombinant proteins tissue_or_cell_type: LIAS and H-protein substrate experimental_model: X-ray structures of catalytic stages with human lipoyl synthase limitations: Structural snapshots establish reaction intermediates, not clinical nutrient requirements. exposure: Structural trapping of sulfur-insertion intermediates evidence_span: {"source_cache": "artifacts/ala-research/40640146.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23", "start_char": 0, "end_char": 953, "text_sha256": "292f83149906d0c3be473ce3b23be4ee13d1c662b2665993808021098523cd23"} [ala-p40640146] Structural basis for catalysis by human lipoyl synthase. (2025). https://pubmed.ncbi.nlm.nih.gov/40640146/ DOI: 10.1038/s41467-025-61393-x
    Complete structured claim and evidence

  4. Reconstituted LIPT1 transfers the lipoyl group from GCSH to dehydrogenase E2 lipoyl domains.

    Human lipoyl amidotransferase / LIPT1 → Human lipoyl-GCSH source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/29987032.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2", "start_char": 0, "end_char": 989, "text_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2"}
    experimental_model
    Purified enzymes and bacterial pathway reconstruction
    exposure
    Recombinant proteins and radiolabeled substrates
    limitations
    Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human proteins; mouse Lipt2 in purified transfer assays; E. coli host
    plain_language
    GCSH carries the cofactor before LIPT1 passes it to energy-processing enzymes.
    primary_references
    [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
    tissue_or_cell_type
    Lipoyl assembly pathway

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 208–219

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes and bacterial pathway reconstruction · source_derived_draft · unverified_draft

    ### ala-lipt1-gcsh-transfer Reconstituted LIPT1 transfers the lipoyl group from GCSH to dehydrogenase E2 lipoyl domains. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: GCSH carries the cofactor before LIPT1 passes it to energy-processing enzymes. organism: Human proteins; mouse Lipt2 in purified transfer assays; E. coli host tissue_or_cell_type: Lipoyl assembly pathway experimental_model: Purified enzymes and bacterial pathway reconstruction limitations: Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy. exposure: Recombinant proteins and radiolabeled substrates evidence_span: {"source_cache": "artifacts/ala-research/29987032.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2", "start_char": 0, "end_char": 989, "text_sha256": "3fc07be493a0d6e22ea55c9509cb2d727180f5921d588a52d2d9300a25aa49a2"} [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
    Complete structured claim and evidence

  5. Purified mouse Lipt2 transferred octanoyl groups from E. coli ACP to human GCSH.

    Mouse octanoyltransferase / Lipt2 → Human octanoyl-GCSH source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/ala-research/29987032.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0569075b59128ea021be6077596127d1c7aae1f9ac6b0acfd2ebcb268b650d3", "start_char": 16562, "end_char": 20381, "text_sha256": "34c5cb398fa99661566112ccf850c1fe0e4a5e74e3aa5b355b1695d12cb7b24d"}
    experimental_model
    Purified enzymes and bacterial pathway reconstruction
    exposure
    Recombinant proteins and radiolabeled substrates
    limitations
    Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human proteins; mouse Lipt2 in purified transfer assays; E. coli host
    plain_language
    The first assembly step loads an eight-carbon precursor onto GCSH.
    primary_references
    [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
    tissue_or_cell_type
    Lipoyl assembly pathway

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 221–232

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified enzymes and bacterial pathway reconstruction · source_derived_draft · unverified_draft

    ### ala-mouse-lipt2-octanoyl-transfer Purified mouse Lipt2 transferred octanoyl groups from E. coli ACP to human GCSH. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first assembly step loads an eight-carbon precursor onto GCSH. organism: Human proteins; mouse Lipt2 in purified transfer assays; E. coli host tissue_or_cell_type: Lipoyl assembly pathway experimental_model: Purified enzymes and bacterial pathway reconstruction limitations: Human and mouse constructs must not be conflated. Recombinant reconstruction establishes chemistry, not supplementation efficacy. exposure: Recombinant proteins and radiolabeled substrates evidence_span: {"source_cache": "artifacts/ala-research/29987032.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0569075b59128ea021be6077596127d1c7aae1f9ac6b0acfd2ebcb268b650d3", "start_char": 16562, "end_char": 20381, "text_sha256": "34c5cb398fa99661566112ccf850c1fe0e4a5e74e3aa5b355b1695d12cb7b24d"} [ala-p29987032] Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. (2018). https://pubmed.ncbi.nlm.nih.gov/29987032/ DOI: 10.1073/pnas.1805862115
    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