Human lipoyl amidotransferase / LIPT1

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

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

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 glycine pathway can keep working when a later transfer step fails.

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 468–479

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-glycine-spared Despite LIPT1 deficiency, H-protein lipoylation, glycine-cleavage activity and glycine concentrations were normal in this case. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The glycine pathway can keep working when a later transfer step fails. 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

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

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

The same exposure changed this marker in opposite directions depending on the cells.

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 481–492

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-lactate-partial-response Lipoic-acid exposure lowered lactate release from the studied LIPT1-deficient fibroblasts, while control-cell lactate increased. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same exposure changed this marker in opposite directions depending on the cells. 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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"}

experimental_model

Engineered bacterial ligase in human knockout cells and a modeled patient allele

exposure

Mitochondrially targeted engineered LplA expression

limitations

Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial.

nutrient_topic

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

organism

Human cells with bacterial enzyme engineering

plain_language

The engineered bypass improved measured cellular function, not just a cofactor stain.

primary_references

[ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995

tissue_or_cell_type

Lipoylation-null cell models and K562 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 572–583

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered bacterial ligase in human knockout cells and a modeled patient allele · source_derived_draft · unverified_draft

### ala-lpla-functional-rescue Engineered LplA restored cellular respiration and growth in low glucose in lipoylation-null cells, including a K562 model of a patient LIPT1 allele. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The engineered bypass improved measured cellular function, not just a cofactor stain. organism: Human cells with bacterial enzyme engineering tissue_or_cell_type: Lipoylation-null cell models and K562 cells experimental_model: Engineered bacterial ligase in human knockout cells and a modeled patient allele limitations: Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial. exposure: Mitochondrially targeted engineered LplA expression evidence_span: {"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"} [ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"}

experimental_model

Engineered bacterial ligase in human knockout cells and a modeled patient allele

exposure

Mitochondrially targeted engineered LplA expression

limitations

Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial.

nutrient_topic

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

organism

Human cells with bacterial enzyme engineering

plain_language

Adding a new enzyme created a route that free supplementation alone did not supply.

primary_references

[ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995

tissue_or_cell_type

Lipoylation-null cell models and K562 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 559–570

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered bacterial ligase in human knockout cells and a modeled patient allele · source_derived_draft · unverified_draft

### ala-lpla-lipoylation-rescue Engineered LplA restored lipoylation in MECR-, BOLA3-, FDX1-, LIAS- and LIPT1-knockout cell models. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding a new enzyme created a route that free supplementation alone did not supply. organism: Human cells with bacterial enzyme engineering tissue_or_cell_type: Lipoylation-null cell models and K562 cells experimental_model: Engineered bacterial ligase in human knockout cells and a modeled patient allele limitations: Experimental genetic engineering, not ordinary supplementation and not a treated-patient efficacy trial. exposure: Mitochondrially targeted engineered LplA expression evidence_span: {"source_cache": "artifacts/ala-research/39547509.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd", "start_char": 0, "end_char": 1884, "text_sha256": "c914532ce06cd71fa946c3aa27935a85d94827215c74ae076a0eebb80ebb45bd"} [ala-p39547509] Engineered bacterial lipoate protein ligase A (lplA) restores lipoylation in cell models of lipoylation deficiency. (2024). https://pubmed.ncbi.nlm.nih.gov/39547509/ DOI: 10.1016/j.jbc.2024.107995