Succinyl-CoA

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

evidence_access

Primary preprint full text; not peer reviewed

experimental_model

Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells.

limitations

Primary preprint, not peer reviewed; fractional tracer contribution is not absolute pathway flux.

nutrient_topic

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

plain_language

Cancer-cell carbon allocation favored one branch of the pathway.

primary_references

A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 474–480

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells. · source_derived_draft · unverified_draft

## isoleucine-pancreatic-preprint-flux Cancer-cell carbon allocation favored one branch of the pathway. A pancreatic-cancer preprint traced isoleucine carbon prominently into propionyl-CoA in mouse KPC and human PDA cell lines, with smaller contributions to acetyl-CoA/succinyl-CoA in those assays. Model: Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells. Limitations: Primary preprint, not peer reviewed; fractional tracer contribution is not absolute pathway flux. Evidence access: Primary preprint full text; not peer reviewed A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

cross_nutrient

B6 and glycine support the porphyrin precursor pathway upstream of iron insertion.

experimental_model

Purified recombinant human ALAS2; crystallography and kinetics

limitations

Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

This B6-dependent step starts erythroid heme synthesis.

primary_references

[b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 799–809

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ALAS2; crystallography and kinetics · source_derived_draft · unverified_draft

### b6-met-alas2-ala Human ALAS2 uses PLP to condense glycine and succinyl-CoA into 5-aminolevulinate, releasing CoA and carbon dioxide. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step starts erythroid heme synthesis. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human ALAS2; crystallography and kinetics limitations: Iron insertion is a later ferrochelatase reaction, not an ALAS2 reaction. cross_nutrient: B6 and glycine support the porphyrin precursor pathway upstream of iron insertion. [b6-alas2-2020] Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release (2020). https://www.nature.com/articles/s41467-020-16586-x DOI: 10.1038/s41467-020-16586-x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Genetic impairment of a B6-dependent enzyme in an iron/heme disorder.

experimental_model

Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays

limitations

Variant-specific in-vitro kinetics do not predict all clinical responses.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

An inherited heme-synthesis defect can impair B6 cofactor use.

primary_references

[b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423

tissue_or_cell_type

Purified recombinant protein; no intact tissue

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 811–821

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays · source_derived_draft · unverified_draft

### b6-met-alas2-r452c ALAS2 Arg452Cys showed reduced PLP affinity and altered succinyl-CoA kinetics despite retained SUCLA2 binding. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inherited heme-synthesis defect can impair B6 cofactor use. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human XLSA variants; recombinant enzyme kinetics and SUCLA2 affinity assays limitations: Variant-specific in-vitro kinetics do not predict all clinical responses. cross_nutrient: Genetic impairment of a B6-dependent enzyme in an iron/heme disorder. [b6-alas2-2012] X-linked Sideroblastic Anemia Due to Carboxyl-terminal ALAS2 Mutations That Cause Loss of Binding to the beta-Subunit of Succinyl-CoA Synthetase (SUCLA2) (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3436539/ DOI: 10.1074/jbc.M111.306423

cross_nutrient

Amino-acid catabolism and central carbon metabolism communicate through an acyl-CoA product.

evidence

[{"paper_key": "nemeria-2018-crosstalk", "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

Reconstituted human enzyme inhibition assays.

limitations

In vitro regulation; physiological free metabolite concentrations and net in vivo effect were not established.

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 product of one B1-dependent route can restrain a different B1 enzyme in a test tube. Its importance inside tissues remains unquantified.

primary_references

[nemeria-2018-crosstalk] Evidence for functional and regulatory cross-talk between the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex and 2-oxoadipate dehydrogenase on the l-lysine, l-hydroxylysine and l-tryptophan degradation pathways from studies in vitro (2018). https://pubmed.ncbi.nlm.nih.gov/29752936/ DOI: 10.1016/j.bbabio.2018.05.001

tissue_or_cell_type

Purified complexes

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 936–948

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

### b1-lysine-product-inhibits-ogdh Glutaryl-CoA inhibited human OGDH activity in reconstituted experiments, supporting possible regulatory communication from OADH-linked amino-acid degradation to the TCA cycle. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A product of one B1-dependent route can restrain a different B1 enzyme in a test tube. Its importance inside tissues remains unquantified. organism: Homo sapiens tissue_or_cell_type: Purified complexes experimental_model: Reconstituted human enzyme inhibition assays. limitations: In vitro regulation; physiological free metabolite concentrations and net in vivo effect were not established. evidence: [{"paper_key": "nemeria-2018-crosstalk", "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: Amino-acid catabolism and central carbon metabolism communicate through an acyl-CoA product. nutrient: Thiamine (vitamin B1) [nemeria-2018-crosstalk] Evidence for functional and regulatory cross-talk between the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex and 2-oxoadipate dehydrogenase on the l-lysine, l-hydroxylysine and l-tryptophan degradation pathways from studies in vitro (2018). https://pubmed.ncbi.nlm.nih.gov/29752936/ DOI: 10.1016/j.bbabio.2018.05.001

cross_nutrient

false

evidence_location

Full text Methods 2.6 and Results 3.6; Figure 5

experimental_model

Human fibroblast lysates overexpressing MCEE and/or MMUT

exposure

Radiolabeled propionyl-CoA; MCEE/MMUT expression and AdoCbl

limitations

Coupled labeled hydrolysis-product assay; MCEE being limiting here is not a universal in-vivo rate limitation.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Human fibroblast assays showed why the epimerase step matters before the B12 enzyme.

primary_references

[heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021

tissue_or_cell_type

Fibroblasts

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1174–1186

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human fibroblast lysates overexpressing MCEE and/or MMUT · source_derived_draft · unverified_draft

### mcee-epimerizes-methylmalonyl-coa Human MCEE interconverts methylmalonyl-CoA epimers, supplying the (R) form for MMUT; MCEE expression increased coupled succinate production. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human fibroblast assays showed why the epimerase step matters before the B12 enzyme. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Human fibroblast lysates overexpressing MCEE and/or MMUT limitations: Coupled labeled hydrolysis-product assay; MCEE being limiting here is not a universal in-vivo rate limitation. exposure: Radiolabeled propionyl-CoA; MCEE/MMUT expression and AdoCbl cross_nutrient: false evidence_location: Full text Methods 2.6 and Results 3.6; Figure 5 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021

cross_nutrient

false

evidence_location

Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods

experimental_model

Purified human proteins

exposure

AdoCbl-loaded MMUT and methylmalonyl-CoA; thiokinase-coupled readout

limitations

Product formation is a coupled assay; cellular net flux was not measured.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Purified human MMUT used activated B12 to make succinyl-CoA from the matching methylmalonyl-CoA epimer.

primary_references

[mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4

tissue_or_cell_type

Purified protein assay

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1103–1115

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

### mmut-isomerizes-r-methylmalonyl-coa Adenosylcobalamin-loaded human MMUT converts (R)-methylmalonyl-CoA to succinyl-CoA in the coupled enzyme assay. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Purified human MMUT used activated B12 to make succinyl-CoA from the matching methylmalonyl-CoA epimer. organism: Homo sapiens tissue_or_cell_type: Purified protein assay experimental_model: Purified human proteins limitations: Product formation is a coupled assay; cellular net flux was not measured. exposure: AdoCbl-loaded MMUT and methylmalonyl-CoA; thiokinase-coupled readout cross_nutrient: false evidence_location: Full text Results; Figures 2-4; cofactor off-loading and MMUT activity Methods [mascarenhas-2023-nanoassembly] Architecture of the human G-protein-methylmalonyl-CoA mutase nanoassembly for B12 delivery and repair. (2023). https://pubmed.ncbi.nlm.nih.gov/37468522/ DOI: 10.1038/s41467-023-40077-4

evidence_access

Primary abstract and indexed full-text introduction, PMC3825524

experimental_model

Human SCOT structure; described ketolysis reaction.

limitations

Production of ketones and ability to use them are different capacities.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

Using ketones requires a separate activation step.

primary_references

A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23420214/ · DOI 10.1007/s10545-013-9589-z

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 144–150

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SCOT structure; described ketolysis reaction. · source_derived_draft · unverified_draft

## fast-scot Using ketones requires a separate activation step. OXCT1 transfers CoA from succinyl-CoA to acetoacetate, yielding acetoacetyl-CoA and succinate. Model: Human SCOT structure; described ketolysis reaction. Limitations: Production of ketones and ability to use them are different capacities. Evidence access: Primary abstract and indexed full-text introduction, PMC3825524 A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23420214/ · DOI 10.1007/s10545-013-9589-z

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"}

experimental_model

Patient-derived cell biochemistry and variant structural analysis

exposure

Compound-heterozygous GLRX5 variants

limitations

One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.

nutrient_topic

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

organism

Human GLRX5-deficient patient

plain_language

A mitochondrial assembly defect may also limit the starting materials used early in heme synthesis.

primary_references

[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012

tissue_or_cell_type

Lymphoblastoid and CD34-positive cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1083–1094

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

### iron-glrx5-alas2 ALAS2 activity was altered in the GLRX5-deficient cells; a problem in succinyl-CoA supply was proposed as a contributor. Condition category: machinery_impairment nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mitochondrial assembly defect may also limit the starting materials used early in heme synthesis. organism: Human GLRX5-deficient patient tissue_or_cell_type: Lymphoblastoid and CD34-positive cells experimental_model: Patient-derived cell biochemistry and variant structural analysis limitations: One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated. exposure: Compound-heterozygous GLRX5 variants evidence_span: {"source_cache": "artifacts/iron-research/30660387.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e", "start_char": 0, "end_char": 1625, "text_sha256": "ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e"} [iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012