Dihydrolipoyl branched-chain transacylase / DBT

cross_nutrient

Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later.

evidence

[{"paper_key": "li-2004-bckdh", "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

Recombinant human E1b and E2b lipoyl domain assays.

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

B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2.

primary_references

[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200

tissue_or_cell_type

Purified proteins

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 773–785

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human E1b and E2b lipoyl domain assays. · source_derived_draft · unverified_draft

### b1-bckdh-ketoacid-acylation Human BCKDH E1 decarboxylates a branched-chain alpha-ketoacid using ThDP and reductively acylates the lipoylated DBT domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Recombinant human E1b and E2b lipoyl domain assays. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "li-2004-bckdh", "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: Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later. nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200

evidence_access

Primary full text, pathway background

experimental_model

Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper.

limitations

Cofactor and catalytic evidence is separately linked from existing ThDP/DLD records.

nutrient_topic

L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine

plain_language

A shared BCAA enzyme commits the carbon skeleton to further breakdown.

primary_references

Clinical and biochemical characterization of four patients with mutations in ECHS1. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26081110/ · DOI 10.1186/s13023-015-0290-1

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 170–176

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper. · source_derived_draft · unverified_draft

## isoleucine-bckdh-carbon-step A shared BCAA enzyme commits the carbon skeleton to further breakdown. The isoleucine pathway in the primary biochemical study places BCKDH-mediated oxidative decarboxylation of the branched ketoacid upstream of 2-methylbutyryl-CoA. Model: Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper. Limitations: Cofactor and catalytic evidence is separately linked from existing ThDP/DLD records. Evidence access: Primary full text, pathway background Clinical and biochemical characterization of four patients with mutations in ECHS1. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26081110/ · DOI 10.1186/s13023-015-0290-1

evidence

[{"paper_key": "li-2004-bckdh", "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 E1b/E2b with recombinant rat BCKD kinase.

limitations

Mixed-species assay; kinase accessibility, not clinical thiamine responsiveness.

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 E1/E2; Rattus norvegicus kinase

plain_language

Cofactor occupancy also affected access to a regulatory site. The result depends on an intact loop and does not show that every genetic BCKDH defect responds to B1.

primary_references

[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200

tissue_or_cell_type

Purified mixed-species assay

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 801–812

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human E1b/E2b with recombinant rat BCKD kinase. · source_derived_draft · unverified_draft

### b1-bckdh-cofactor-limits-phosphorylation ThDP reduced kinase-mediated phosphorylation of wild-type human E1b; loop-network mutations abolished this protection in the reconstituted assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor occupancy also affected access to a regulatory site. The result depends on an intact loop and does not show that every genetic BCKDH defect responds to B1. organism: Homo sapiens E1/E2; Rattus norvegicus kinase tissue_or_cell_type: Purified mixed-species assay experimental_model: Human E1b/E2b with recombinant rat BCKD kinase. limitations: Mixed-species assay; kinase accessibility, not clinical thiamine responsiveness. evidence: [{"paper_key": "li-2004-bckdh", "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."}] nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200

cross_nutrient

ThDP occupancy enables interaction with the lipoylated E2 carrier.

evidence

[{"paper_key": "li-2004-bckdh", "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 apo/holo E1b crystallography and lipoyl-domain binding.

limitations

Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response.

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

B1 binding changes the enzyme shape so it can receive its lipoyl partner.

primary_references

[li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200

tissue_or_cell_type

Purified proteins

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 787–799

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human apo/holo E1b crystallography and lipoyl-domain binding. · source_derived_draft · unverified_draft

### b1-bckdh-thdp-orders-loop Apo/holo human E1b structures showed that ThDP binding orders the phosphorylation loop needed to recognize the lipoylated E2b domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 binding changes the enzyme shape so it can receive its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human apo/holo E1b crystallography and lipoyl-domain binding. limitations: Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response. evidence: [{"paper_key": "li-2004-bckdh", "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: ThDP occupancy enables interaction with the lipoylated E2 carrier. nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/ala-research/24341803.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b", "start_char": 19977, "end_char": 20689, "text_sha256": "3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79"}

experimental_model

LIPT1 patient fibroblasts with supplementation and genetic complementation

exposure

Lipoic acid 10 or 100 micromolar for three weeks

limitations

Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology.

nutrient_topic

Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid

organism

Human

plain_language

A lower lactate measurement did not mean all affected enzyme systems were repaired.

primary_references

[ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192

tissue_or_cell_type

Patient and control fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling 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 · LIPT1 patient fibroblasts with supplementation and genetic complementation · source_derived_draft · unverified_draft

### ala-lipt1-enzyme-partial-response In those LIPT1-deficient fibroblasts, PDH activity increased only moderately, OGDH showed no increase, and the leucine-flux assay showed no BCKDH rescue. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower lactate measurement did not mean all affected enzyme systems were repaired. organism: Human tissue_or_cell_type: Patient and control fibroblasts experimental_model: LIPT1 patient fibroblasts with supplementation and genetic complementation limitations: Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology. exposure: Lipoic acid 10 or 100 micromolar for three weeks evidence_span: {"source_cache": "artifacts/ala-research/24341803.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b", "start_char": 19977, "end_char": 20689, "text_sha256": "3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79"} [ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192