Component

Dihydrolipoyl acetyltransferase / DLAT

Human E2 catalytic subunit of pyruvate dehydrogenase complex.

12 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. 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. The abstract reports DLAT binding to SLC25A39 in colorectal cancer models.

    Dihydrolipoyl acetyltransferase / DLAT → Human mitochondrial glutathione carrier SLC25A39 source_derived_draftungraded
    Experimental context and source evidence
    access_level
    abstract_only
    compartment
    Mitochondrial GSH versus intracellular GSH distinguished by authors
    dose
    Unknown: full methods unavailable
    duration
    Unknown: full methods unavailable
    endpoint
    slc25a39
    evidence_location
    Primary indexed abstract; experiment-specific methods unavailable
    experimental_model
    Protein interaction/stability, knockdown and compound experiments reported in abstract
    exposure
    dlat
    limitations
    ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
    nutrient_topic
    Topical cross-reference only; no inheritance of another actor's effects. · GSH
    organism
    Human colorectal cancer models; individual experiments require full-text confirmation
    plain_language
    The abstract reports DLAT binding to SLC25A39 in colorectal cancer models.
    primary_locator
    [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
    primary_references
    https://doi.org/10.1016/j.freeradbiomed.2026.04.133
    tissue_or_cell_type
    Colorectal cancer models; claim-specific cell line not established from abstract

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 716–730

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft

    The abstract reports DLAT binding to SLC25A39 in colorectal cancer models. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: slc25a39 exposure: dlat limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: The abstract reports DLAT binding to SLC25A39 in colorectal cancer models.
    Complete structured claim and evidence

  3. The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.

    Dihydrolipoyl acetyltransferase / DLAT → Mammalian mitochondrial glutathione import source_derived_draftungraded
    Experimental context and source evidence
    access_level
    abstract_only
    compartment
    Mitochondrial GSH versus intracellular GSH distinguished by authors
    dose
    Unknown: full methods unavailable
    duration
    Unknown: full methods unavailable
    endpoint
    mitochondrial-gsh-import
    evidence_location
    Primary indexed abstract; experiment-specific methods unavailable
    experimental_model
    Protein interaction/stability, knockdown and compound experiments reported in abstract
    exposure
    dlat
    limitations
    ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Mechanistic interpretation reported in abstract; mediation/rescue controls cannot be assessed without full text.
    nutrient_topic
    Topical cross-reference only; no inheritance of another actor's effects. · GSH
    organism
    Human colorectal cancer models; individual experiments require full-text confirmation
    plain_language
    The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.
    primary_locator
    [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
    primary_references
    https://doi.org/10.1016/j.freeradbiomed.2026.04.133
    tissue_or_cell_type
    Colorectal cancer models; claim-specific cell line not established from abstract

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 750–764

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft

    The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: mitochondrial-gsh-import exposure: dlat limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Mechanistic interpretation reported in abstract; mediation/rescue controls cannot be assessed without full text. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.
    Complete structured claim and evidence

  4. DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels.

    Dihydrolipoyl acetyltransferase / DLAT → SLC25A39 protein stability source_derived_draftungraded
    Experimental context and source evidence
    access_level
    abstract_only
    compartment
    Mitochondrial GSH versus intracellular GSH distinguished by authors
    dose
    Unknown: full methods unavailable
    duration
    Unknown: full methods unavailable
    endpoint
    slc25a39-protein-stability
    evidence_location
    Primary indexed abstract; experiment-specific methods unavailable
    experimental_model
    Protein interaction/stability, knockdown and compound experiments reported in abstract
    exposure
    dlat
    limitations
    ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
    nutrient_topic
    Topical cross-reference only; no inheritance of another actor's effects. · GSH
    organism
    Human colorectal cancer models; individual experiments require full-text confirmation
    plain_language
    DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels.
    primary_locator
    [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
    primary_references
    https://doi.org/10.1016/j.freeradbiomed.2026.04.133
    tissue_or_cell_type
    Colorectal cancer models; claim-specific cell line not established from abstract

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 733–747

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft

    DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: slc25a39-protein-stability exposure: dlat limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels.
    Complete structured claim and evidence

What acts on it

  1. Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation.

    Human pyruvate dehydrogenase E1 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested.
    evidence
    [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Human recombinant proteins; radiolabeled pyruvate assay.
    limitations
    Purified-system evidence; nutritional response was not tested.
    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 B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction.
    primary_references
    [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    tissue_or_cell_type
    Purified proteins

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 676–688

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant proteins; radiolabeled pyruvate assay. · source_derived_draft · unverified_draft

    ### b1-pdh-lipoyl-acetyl-transfer Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human recombinant proteins; radiolabeled pyruvate assay. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested. nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    Complete structured claim and evidence

  2. Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay.

    PDH E1 phosphorylated at alpha Ser264 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
    Experimental context and source evidence
    evidence
    [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Engineered human site-1-only E1; phosphorylation, ITC and kinetics.
    limitations
    Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse 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
    Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner.
    primary_references
    [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    tissue_or_cell_type
    Purified proteins

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 704–715

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered human site-1-only E1; phosphorylation, ITC and kinetics. · source_derived_draft · unverified_draft

    ### b1-pdh-phosphorylation-blocks-lipoyl-recognition Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Engineered human site-1-only E1; phosphorylation, ITC and kinetics. limitations: Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse experiment. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    Complete structured claim and evidence

  3. GL-V9 reportedly bound DLAT.

    GL-V9 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
    Experimental context and source evidence
    access_level
    abstract_only
    compartment
    Mitochondrial GSH versus intracellular GSH distinguished by authors
    dose
    Unknown: full methods unavailable
    duration
    Unknown: full methods unavailable
    endpoint
    dlat
    evidence_location
    Primary indexed abstract; experiment-specific methods unavailable
    experimental_model
    Protein interaction/stability, knockdown and compound experiments reported in abstract
    exposure
    gl-v9
    limitations
    ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
    nutrient_topic
    Topical cross-reference only; no inheritance of another actor's effects. · GSH
    organism
    Human colorectal cancer models; individual experiments require full-text confirmation
    plain_language
    GL-V9 reportedly bound DLAT.
    primary_locator
    [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
    primary_references
    https://doi.org/10.1016/j.freeradbiomed.2026.04.133
    tissue_or_cell_type
    Colorectal cancer models; claim-specific cell line not established from abstract

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 869–883

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft

    GL-V9 reportedly bound DLAT. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: dlat exposure: gl-v9 limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: GL-V9 reportedly bound DLAT.
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations.

    LIAS Arg249His → Human pyruvate dehydrogenase complex source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway.
    evidence
    [{"paper_key": "mayr-2011-lias", "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
    Patient biochemical analysis.
    limitations
    Single patient; no proof of thiamine-treatment failure mechanism.
    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
    A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect.
    primary_references
    [mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011
    tissue_or_cell_type
    Muscle and cultured fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 759–771

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient biochemical analysis. · source_derived_draft · unverified_draft

    ### b1-lias-defect-reduces-pdh The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect. organism: Homo sapiens tissue_or_cell_type: Muscle and cultured fibroblasts experimental_model: Patient biochemical analysis. limitations: Single patient; no proof of thiamine-treatment failure mechanism. evidence: [{"paper_key": "mayr-2011-lias", "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: Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway. nutrient: Thiamine (vitamin B1) [mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011
    Complete structured claim and evidence

  2. The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1.

    Human lipoyl amidotransferase / LIPT1 → Mitochondrial protein lipoylation source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"}
    experimental_model
    Affected patient, biochemical testing and complementation
    exposure
    Compound-heterozygous LIPT1 variants
    limitations
    Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency.
    nutrient_topic
    Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
    organism
    Human
    plain_language
    The cofactor was not reaching the dehydrogenase machinery.
    primary_references
    [ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
    tissue_or_cell_type
    Patient-derived cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 455–466

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affected patient, biochemical testing and complementation · source_derived_draft · unverified_draft

    ### ala-lipt1-e2-loss The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor was not reaching the dehydrogenase machinery. organism: Human tissue_or_cell_type: Patient-derived cells experimental_model: Affected patient, biochemical testing and complementation limitations: Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency. exposure: Compound-heterozygous LIPT1 variants evidence_span: {"source_cache": "artifacts/ala-research/24256811.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2", "start_char": 0, "end_char": 1749, "text_sha256": "57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2"} [ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585
    Complete structured claim and evidence

  3. 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

  4. GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT.

    GL-V9 → DLAT ubiquitin-proteasome degradation source_derived_draftungraded
    Experimental context and source evidence
    access_level
    abstract_only
    compartment
    Mitochondrial GSH versus intracellular GSH distinguished by authors
    dose
    Unknown: full methods unavailable
    duration
    Unknown: full methods unavailable
    endpoint
    dlat-ubiquitin-proteasome-degradation
    evidence_location
    Primary indexed abstract; experiment-specific methods unavailable
    experimental_model
    Protein interaction/stability, knockdown and compound experiments reported in abstract
    exposure
    gl-v9
    limitations
    ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
    nutrient_topic
    Topical cross-reference only; no inheritance of another actor's effects. · GSH
    organism
    Human colorectal cancer models; individual experiments require full-text confirmation
    plain_language
    GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT.
    primary_locator
    [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
    primary_references
    https://doi.org/10.1016/j.freeradbiomed.2026.04.133
    tissue_or_cell_type
    Colorectal cancer models; claim-specific cell line not established from abstract

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 886–900

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft

    GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: dlat-ubiquitin-proteasome-degradation exposure: gl-v9 limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT.
    Complete structured claim and evidence

  5. The five surgical atrial samples showed higher HADHA acetylation in the three obese samples, but DLAT was higher in only two of those three.

    Obese versus non-obese CABG right-atrial tissue samples → Human right-atrial HADHA lysine acetylation source_derived_draftungraded
    Experimental context and source evidence
    access_level
    full_text_and_supplement_review
    compartment
    Right atrial tissue lysate
    dose
    No experimental drug or nutrient exposure
    duration
    Single sampling at surgery
    endpoint
    human-atrial-hadha-acetylation
    evidence_location
    Supplementary Table S1 and Figure S20, visually inspected
    experimental_model
    Cross-sectional convenience sample: 3 obese and 2 non-obese surgical patients
    exposure
    human-obesity-cabg-samples
    limitations
    Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Descriptive convenience sample, not a validated correlation or causal human-heart intervention. Right atrium is not left ventricle. A review response assigns an inconsistent heart-failure label; no diagnosis is inferred from that wording.
    organism
    Homo sapiens
    plain_language
    The five surgical atrial samples showed higher HADHA acetylation in the three obese samples, but DLAT was higher in only two of those three.
    primary_locator
    [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 104, "text_sha256": "ae51373bee14359b2ba2ca7de36bd5414f6a04956020ac189c94fe8fd37ead43", "xml_element_id": "Par47"}, {"cache": "artifacts/dlat-curation/41467_2026_70703_MOESM1_ESM.pdf", "location": "Supplementary Table S1 and Figure S20", "sha256": "82754f96eebe642d7dcc3a4c7a1c9e3437da00a14aa6c7bfb67b369c5a927c90"}]
    primary_references
    https://doi.org/10.1038/s41467-026-70703-w
    sample_size
    3 obese; 2 non-obese
    tissue_or_cell_type
    Right atrial tissue collected during CABG

    DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 698–713

    AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Cross-sectional convenience sample: 3 obese and 2 non-obese surgical patients · source_derived_draft · unverified_draft

    The five surgical atrial samples showed higher HADHA acetylation in the three obese samples, but DLAT was higher in only two of those three. organism: Homo sapiens tissue_or_cell_type: Right atrial tissue collected during CABG experimental_model: Cross-sectional convenience sample: 3 obese and 2 non-obese surgical patients compartment: Right atrial tissue lysate dose: No experimental drug or nutrient exposure duration: Single sampling at surgery primary_references: https://doi.org/10.1038/s41467-026-70703-w access_level: full_text_and_supplement_review evidence_location: Supplementary Table S1 and Figure S20, visually inspected endpoint: human-atrial-hadha-acetylation exposure: human-obesity-cabg-samples limitations: Single primary study; not independently replicated here. Cardiac and recombinant findings do not establish pulmonary endothelial, viral-sepsis or ARDS effects. Descriptive convenience sample, not a validated correlation or causal human-heart intervention. Right atrium is not left ventricle. A review response assigns an inconsistent heart-failure label; no diagnosis is inferred from that wording. primary_locator: [{"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 44, "text_sha256": "e0a92f47bc76c894816706ffb5158242c968928ac61e4561262c370035eda621", "xml_element_id": "Par19"}, {"cache": "artifacts/dlat-curation/heart-blocks.json", "block_index": 104, "text_sha256": "ae51373bee14359b2ba2ca7de36bd5414f6a04956020ac189c94fe8fd37ead43", "xml_element_id": "Par47"}, {"cache": "artifacts/dlat-curation/41467_2026_70703_MOESM1_ESM.pdf", "location": "Supplementary Table S1 and Figure S20", "sha256": "82754f96eebe642d7dcc3a4c7a1c9e3437da00a14aa6c7bfb67b369c5a927c90"}] plain_language: The five surgical atrial samples showed higher HADHA acetylation in the three obese samples, but DLAT was higher in only two of those three. sample_size: 3 obese; 2 non-obese
    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