2-Oxoglutarate dehydrogenase complex

cross_nutrient

B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex.

evidence

[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Reconstituted human multienzyme assay.

limitations

NADH assay measures overall complex turnover, not every intermediate independently.

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-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD.

primary_references

[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

tissue_or_cell_type

Purified enzyme complex

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 855–867

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human multienzyme assay. · source_derived_draft · unverified_draft

### b1-ogdh-complex-couples-succinyl-nadh Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD. organism: Homo sapiens tissue_or_cell_type: Purified enzyme complex experimental_model: Reconstituted human multienzyme assay. limitations: NADH assay measures overall complex turnover, not every intermediate independently. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex. nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments.

limitations

The paper assigns more than one inhibitory mechanism; their in vivo contributions were not measured.

nutrient_topic

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

organism

Sus scrofa

plain_language

ATP concentration can alter both free magnesium and nucleotide regulation of the enzyme.

primary_references

[rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856

tissue_or_cell_type

Isolated heart enzyme; additional mitochondrial-extract source not resolved

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 711–721

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. · source_derived_draft · unverified_draft

### mg-ogdh-atp-chelation-inhibition The 2000 study attributed ATP inhibition to Mg chelation and an inhibitory effect of MgATP. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP concentration can alter both free magnesium and nucleotide regulation of the enzyme. organism: Sus scrofa tissue_or_cell_type: Isolated heart enzyme; additional mitochondrial-extract source not resolved experimental_model: Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. limitations: The paper assigns more than one inhibitory mechanism; their in vivo contributions were not measured. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856

cross_nutrient

Calcium and magnesium effects on a thiamine-dependent enzyme were additive under specified assay conditions.

experimental_model

Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations.

limitations

Additivity depended on concentration; it does not imply Ca replaces Mg at the ThDP site.

nutrient_topic

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

organism

Sus scrofa

plain_language

Calcium regulation and magnesium support can act together in the enzyme preparation.

primary_references

[panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

tissue_or_cell_type

Purified heart mitochondrial enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 687–697

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. · source_derived_draft · unverified_draft

### mg-ogdh-calcium-additivity Ca and Mg stimulation of purified pig-heart KGDHC was additive over the tested lower free-ion ranges. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium regulation and magnesium support can act together in the enzyme preparation. organism: Sus scrofa tissue_or_cell_type: Purified heart mitochondrial enzyme experimental_model: Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. limitations: Additivity depended on concentration; it does not imply Ca replaces Mg at the ThDP site. cross_nutrient: Calcium and magnesium effects on a thiamine-dependent enzyme were additive under specified assay conditions. [panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets.

limitations

Computational inference, not a new binding measurement; more complex alternatives were not excluded.

nutrient_topic

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

organism

Mammalian datasets including Sus scrofa

plain_language

One model explains activation using two separate regulators.

primary_references

[qi-2011-ogdh] Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase (2011). https://link.springer.com/article/10.1186/1471-2091-12-53 DOI: 10.1186/1471-2091-12-53

tissue_or_cell_type

Published isolated-enzyme datasets

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 723–733

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets. · source_derived_draft · unverified_draft

### mg-ogdh-independent-adp-model A 2011 kinetic reanalysis favored independent Mg and ADP effects rather than requiring MgADP as the activating species. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: One model explains activation using two separate regulators. organism: Mammalian datasets including Sus scrofa tissue_or_cell_type: Published isolated-enzyme datasets experimental_model: Primary kinetic modeling and reanalysis of published mammalian OGDHC datasets. limitations: Computational inference, not a new binding measurement; more complex alternatives were not excluded. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [qi-2011-ogdh] Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase (2011). https://link.springer.com/article/10.1186/1471-2091-12-53 DOI: 10.1186/1471-2091-12-53

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments.

limitations

Speciation-based interpretation; later modeling offered independent Mg/ADP effects.

nutrient_topic

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

organism

Sus scrofa

plain_language

The authors assigned enhanced activity to magnesium-bound ADP.

primary_references

[rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856

tissue_or_cell_type

Isolated heart enzyme; additional mitochondrial-extract source not resolved

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 699–709

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. · source_derived_draft · unverified_draft

### mg-ogdh-mgadp-interpretation The 2000 experiments interpreted MgADP as a more potent OGDHC activator than free ADP. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The authors assigned enhanced activity to magnesium-bound ADP. organism: Sus scrofa tissue_or_cell_type: Isolated heart enzyme; additional mitochondrial-extract source not resolved experimental_model: Isolated pig-heart enzyme complex plus mitochondrial extracts; extract source not resolved in this curation; nucleotide/phosphate/Mg speciation experiments. limitations: Speciation-based interpretation; later modeling offered independent Mg/ADP effects. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [rodriguez-2000-ogdh] Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg(2+), and other effectors (2000). https://pubmed.ncbi.nlm.nih.gov/10864444/ DOI: 10.1006/abbi.2000.1856

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations.

limitations

Absence of added cofactor does not establish that all tightly bound cofactor was removed.

nutrient_topic

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

organism

Sus scrofa

plain_language

Magnesium and the B1-derived cofactor jointly supported maximal enzyme activity.

primary_references

[panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

tissue_or_cell_type

Purified heart mitochondrial enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 675–685

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. · source_derived_draft · unverified_draft

### mg-ogdh-stimulation-requires-thdp Mg increased purified pig-heart KGDHC activity only when ThDP was present in the assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and the B1-derived cofactor jointly supported maximal enzyme activity. organism: Sus scrofa tissue_or_cell_type: Purified heart mitochondrial enzyme experimental_model: Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. limitations: Absence of added cofactor does not establish that all tightly bound cofactor was removed. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]

experimental_model

Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.

exposure

Riboflavin-free medium compared with matched replete medium.

limitations

No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.

primary_references

[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

tissue_or_cell_type

143B cell proteomics

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–634

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft

### b2-met-depletion-dld DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme. organism: Homo sapiens tissue_or_cell_type: 143B cell proteomics experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins. exposure: Riboflavin-free medium compared with matched replete medium. cross_nutrient: Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"}

experimental_model

Three affected children from two families and patient-derived fibroblasts

exposure

Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation

limitations

Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.

nutrient_topic

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

organism

Human

plain_language

One early assembly failure disrupts carbohydrate and amino-acid processing.

primary_references

[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001

tissue_or_cell_type

Patient cells and clinical phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 429–440

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three affected children from two families and patient-derived fibroblasts · source_derived_draft · unverified_draft

### ala-lipt2-multienzyme-failure LIPT2-deficient fibroblasts had reduced PDH and OGDH activities, oxygen consumption and leucine catabolic flux. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: One early assembly failure disrupts carbohydrate and amino-acid processing. organism: Human tissue_or_cell_type: Patient cells and clinical phenotype experimental_model: Three affected children from two families and patient-derived fibroblasts limitations: Rare inherited disease; not evidence for common dietary lipoic-acid deficiency. exposure: Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation evidence_span: {"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"} [ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Three affected children from two families and patient-derived fibroblasts

exposure

Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation

limitations

Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.

nutrient_topic

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

organism

Human

plain_language

More free lipoic acid did not bypass the broken assembly step.

primary_references

[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001

tissue_or_cell_type

Patient cells and clinical phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 442–453

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three affected children from two families and patient-derived fibroblasts · source_derived_draft · unverified_draft

### ala-lipt2-supplement-no-rescue Lipoic acid supplementation did not improve the reported clinical course or restore deficient PDH, OGDH and leucine-catabolic function in LIPT2-deficient fibroblasts. Condition category: machinery_impairment nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: More free lipoic acid did not bypass the broken assembly step. organism: Human tissue_or_cell_type: Patient cells and clinical phenotype experimental_model: Three affected children from two families and patient-derived fibroblasts limitations: Rare inherited disease; not evidence for common dietary lipoic-acid deficiency. exposure: Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation evidence_span: {"source_cache": "artifacts/ala-research/28757203.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f", "start_char": 0, "end_char": 1639, "text_sha256": "a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f"} [ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001

evidence_access

Primary full text

experimental_model

Isolated human mitochondria; inhibitor combinations used to distinguish ROS-generating sites.

limitations

Results in Drosophila instead emphasized complexes I and II; these species-specific observations do not identify a universal source.

nutrient_topic

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

plain_language

A pathway can increase ROS without its first enzyme being the direct ROS-producing site.

primary_references

Sources of superoxide/H2O2 during mitochondrial proline oxidation. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25184115/ · DOI 10.1016/j.redox.2014.07.003

L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 142–148

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated human mitochondria; inhibitor combinations used to distinguish ROS-generating sites. · source_derived_draft · unverified_draft

## l-proline-ros-source-boundary A pathway can increase ROS without its first enzyme being the direct ROS-producing site. During proline oxidation in ZR75-30 mitochondria, the main measured ROS sources were complex I and 2-oxoglutarate dehydrogenase, with no significant direct PRODH contribution under the tested substrate/inhibitor conditions. Model: Isolated human mitochondria; inhibitor combinations used to distinguish ROS-generating sites. Limitations: Results in Drosophila instead emphasized complexes I and II; these species-specific observations do not identify a universal source. Evidence access: Primary full text Sources of superoxide/H2O2 during mitochondrial proline oxidation. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25184115/ · DOI 10.1016/j.redox.2014.07.003