Protein-bound oxidized lipoyl-lysine

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 5507, "end_char": 5866, "text_sha256": "77f0d121a0aed5bdcd3c4898c369533a29208ebd8a9450a3a37ceff5d783c3af"}

experimental_model

Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria

exposure

Slc25a3 deletion and elesclomol-copper exposure

limitations

Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology.

nutrient_topic

Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper

organism

Rat H9c2 cells; human SLC25A3 in Lactococcus lactis

plain_language

Misplaced copper damaged proteins that normally carry lipoamide.

primary_references

[copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123

tissue_or_cell_type

Mitochondria; bacterial copper export assay

trigger_kind

machinery_impairment Imported condition classification; unverified.

Copper: transport, cuproenzymes, deficiency, excess 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 · Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria · source_derived_draft · unverified_draft

### copper-slc25a3-es-dlat Slc25a3-null rat cells exposed to elesclomol-copper showed increased DLAT oligomerization and loss of lipoylated DLAT and DLST. Condition category: machinery_impairment nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Misplaced copper damaged proteins that normally carry lipoamide. organism: Rat H9c2 cells; human SLC25A3 in Lactococcus lactis tissue_or_cell_type: Mitochondria; bacterial copper export assay experimental_model: Rat Slc25a3 knockout cardiomyoblasts and human transporter expression in bacteria limitations: Whole-organelle copper was measured, not separate matrix and intermembrane pools. Matrix trapping is the authors mechanism inferred with transport evidence. This recent study complements import findings; bacterial export does not reproduce mitochondrial topology. exposure: Slc25a3 deletion and elesclomol-copper exposure evidence_span: {"source_cache": "artifacts/copper-research/42308035.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0c19d3c109f1df88791ad51c22e6acf85b7d5ffe5c26c74aaaf5e3222a75c054", "start_char": 5507, "end_char": 5866, "text_sha256": "77f0d121a0aed5bdcd3c4898c369533a29208ebd8a9450a3a37ceff5d783c3af"} [copper-p42308035] SLC25A3 exports mitochondrial copper to metalate cytochrome c oxidase and prevent cuproptosis. (2026). https://pubmed.ncbi.nlm.nih.gov/42308035/ DOI: 10.1073/pnas.2612098123

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

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

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Full text line 47; Supplementary Fig. S4B

experimental_model

Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria

exposure

Cardiomyocyte-specific Ndufab1 deletion.

limitations

A null result for these measurements is not proof that all fatty-acid synthesis was intact. Different tissue, developmental timing and depletion conditions preclude a same-context contradiction with HEK293T cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Mus musculus

plain_language

Mouse heart respiratory failure occurred without the measured lipoylation defect seen in the cultured-cell study.

primary_references

[b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x

tissue_or_cell_type

Heart mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 977–989

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria · source_derived_draft · unverified_draft

### b5-met-heart-acp-lipoylation-spared In the cardiac Ndufab1-knockout study, the measured mitochondrial protein lipoylation was not significantly changed despite respiratory defects. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse heart respiratory failure occurred without the measured lipoylation defect seen in the cultured-cell study. organism: Mus musculus tissue_or_cell_type: Heart mitochondria experimental_model: Cardiomyocyte-specific Ndufab1 knockout mice and isolated heart mitochondria limitations: A null result for these measurements is not proof that all fatty-acid synthesis was intact. Different tissue, developmental timing and depletion conditions preclude a same-context contradiction with HEK293T cells. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Cardiomyocyte-specific Ndufab1 deletion. cross_nutrient: true evidence_location: Full text line 47; Supplementary Fig. S4B [b5-met-ndufab2019] NDUFAB1 confers cardio-protection by enhancing mitochondrial bioenergetics through coordination of respiratory complex and supercomplex assembly. (2019). https://pubmed.ncbi.nlm.nih.gov/31366990/ DOI: 10.1038/s41422-019-0208-x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Abstract, lipoic-acid supplementation result

experimental_model

Mitochondrial ACP siRNA in HEK293T cells

exposure

Lipoic-acid supplementation of ACP-knockdown cultures; concentration not extracted.

limitations

Lipoic acid offered some oxidative-damage protection, but that is a different endpoint; result is not a universal statement about every lipoylation disorder. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

External lipoic acid did not bypass this carrier-protein defect.

primary_references

[b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200

tissue_or_cell_type

HEK293T cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 851–863

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial ACP siRNA in HEK293T cells · source_derived_draft · unverified_draft

### b5-met-lipoate-nonrescue Adding lipoic acid to the culture medium did not reverse the protein-lipoylation defect caused by mitochondrial ACP knockdown in HEK293T cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: External lipoic acid did not bypass this carrier-protein defect. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Lipoic acid offered some oxidative-damage protection, but that is a different endpoint; result is not a universal statement about every lipoylation disorder. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: Lipoic-acid supplementation of ACP-knockdown cultures; concentration not extracted. cross_nutrient: true evidence_location: Abstract, lipoic-acid supplementation result [b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Abstract, earliest phenotypic changes; Fig. 2 caption

experimental_model

Mitochondrial ACP siRNA in HEK293T cells

exposure

ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown.

limitations

Antibody-based lipoylation readout; not a measurement of dietary lipoic acid or pantothenate shortage. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

Loss of the mitochondrial carrier impaired attachment of the lipoate cofactor to proteins.

primary_references

[b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200

tissue_or_cell_type

HEK293T mitochondrial proteins

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 823–835

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mitochondrial ACP siRNA in HEK293T cells · source_derived_draft · unverified_draft

### b5-met-mtacp-lipoylation Mitochondrial ACP knockdown in HEK293T cells reduced the proportion of mitochondrial proteins recognized as lipoylated before later respiratory defects. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of the mitochondrial carrier impaired attachment of the lipoate cofactor to proteins. organism: Homo sapiens tissue_or_cell_type: HEK293T mitochondrial proteins experimental_model: Mitochondrial ACP siRNA in HEK293T cells limitations: Antibody-based lipoylation readout; not a measurement of dietary lipoic acid or pantothenate shortage. This experiment does not establish a dietary pantothenate threshold or benefit from B5 supplementation. exposure: ACP mRNA and protein reduced by more than 85% within 24 hours; later measurements followed knockdown. cross_nutrient: true evidence_location: Abstract, earliest phenotypic changes; Fig. 2 caption [b5-met-acp2009] Down-regulation of mitochondrial acyl carrier protein in mammalian cells compromises protein lipoylation and respiratory complex I and results in cell death. (2009). https://pubmed.ncbi.nlm.nih.gov/19221180/ DOI: 10.1074/jbc.m806991200