Component

Protein-bound reduced dihydrolipoyl-lysine

Reduced dithiol form of a protein-linked lipoyl group.

3 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. Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.

    DLD → Protein-bound reduced dihydrolipoyl-lysine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.
    evidence
    [{"paper_key": "brautigam-2005-dld", "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
    Human DLD crystallography with NAD+ and NADH.
    limitations
    Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.
    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
    The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.
    primary_references
    [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
    tissue_or_cell_type
    Purified enzyme

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–729

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLD crystallography with NAD+ and NADH. · source_derived_draft · unverified_draft

    ### b1-dld-fad-nad-lipoyl-regeneration Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human DLD crystallography with NAD+ and NADH. limitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency. evidence: [{"paper_key": "brautigam-2005-dld", "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: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction. nutrient: Thiamine (vitamin B1) [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation.

    Dihydrolipoyl acetyltransferase / DLAT → Coenzyme A source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B1-dependent E1 and B5-derived CoA participate in different sequential steps.
    evidence
    [{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Human DLAT cryo-EM; bacterial ligand poses used for modeling.
    limitations
    Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment.
    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
    After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier.
    primary_references
    [jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357
    tissue_or_cell_type
    Purified catalytic core

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 690–702

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DLAT cryo-EM; bacterial ligand poses used for modeling. · source_derived_draft · unverified_draft

    ### b1-pdh-dlat-coa-acetylation The human DLAT catalytic core contains a channel for the acetylated lipoyl group and CoA; substrate modeling positions CoA for acetyl-CoA formation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: After B1 acts at E1, the E2 protein transfers the acetyl group onto CoA, a vitamin B5-derived carrier. organism: Homo sapiens tissue_or_cell_type: Purified catalytic core experimental_model: Human DLAT cryo-EM; bacterial ligand poses used for modeling. limitations: Ligand positions were modeled, not directly resolved in a human substrate-bound structure; no intake experiment. evidence: [{"paper_key": "jiang-2018-pdh-core", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "acetyl-accepting CoA", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent E1 and B5-derived CoA participate in different sequential steps. nutrient: Thiamine (vitamin B1) [jiang-2018-pdh-core] Atomic Structure of the E2 Inner Core of Human Pyruvate Dehydrogenase Complex (2018). https://pubmed.ncbi.nlm.nih.gov/29608861/ DOI: 10.1021/acs.biochem.8b00357
    Complete structured claim and evidence

  2. Purified human DLD I12T retained about 0.15 FAD per monomer versus approximately one in wild type, with forward and reverse activities of about 8% and 2%.

    Human DLD Ile12Thr → FAD source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    DLD is reused from the B1 complexes; its flavin/NAD step is distinct from upstream thiamine diphosphate chemistry.
    evidence_spans
    [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 19, "char_start": 0, "char_end": 871, "evidence_access": "full-text"}]
    experimental_model
    Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography.
    exposure
    I12T mutagenesis, purified-protein FAD and activity assays.
    limitations
    Purification instability can affect measured occupancy; correlation does not prove FAD loss alone caused all activity loss.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    This DLD variant poorly retained FAD and had very low catalytic activity.
    primary_references
    [szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
    tissue_or_cell_type
    Recombinant DLD expressed in E. coli
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 847–859

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. · source_derived_draft · unverified_draft

    ### b2-met-dld-i12t-fad-retention Purified human DLD I12T retained about 0.15 FAD per monomer versus approximately one in wild type, with forward and reverse activities of about 8% and 2%. Condition category: machinery_impairment nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This DLD variant poorly retained FAD and had very low catalytic activity. organism: Homo sapiens tissue_or_cell_type: Recombinant DLD expressed in E. coli experimental_model: Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography. limitations: Purification instability can affect measured occupancy; correlation does not prove FAD loss alone caused all activity loss. exposure: I12T mutagenesis, purified-protein FAD and activity assays. cross_nutrient: DLD is reused from the B1 complexes; its flavin/NAD step is distinct from upstream thiamine diphosphate chemistry. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10341545", "locator": "XML .//body//p", "paragraph_index": 19, "char_start": 0, "char_end": 871, "evidence_access": "full-text"}] [szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826
    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