Succinate

evidence_access

Primary full text

experimental_model

Recombinant human ATCase kinetic experiments with succinate and substrate titration.

limitations

This is not proof that ordinary dietary succinate or aspartate concentrations cause the same inhibition in a person.

nutrient_topic

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

plain_language

An accumulated carbon-cycle metabolite competes with aspartate at a nucleotide-making enzyme.

primary_references

Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 210–216

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human ATCase kinetic experiments with succinate and substrate titration. · source_derived_draft · unverified_draft

## l-aspartate-succinate-atcase An accumulated carbon-cycle metabolite competes with aspartate at a nucleotide-making enzyme. Succinate competitively inhibited aspartate utilization by the purified human CAD ATCase domain. Model: Recombinant human ATCase kinetic experiments with succinate and substrate titration. Limitations: This is not proof that ordinary dietary succinate or aspartate concentrations cause the same inhibition in a person. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w

evidence_span

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experimental_model

Review of a clinical database cohort following identification of a patient diagnosed in the seventh decade

exposure

Naturally occurring succinic semialdehyde dehydrogenase deficiency followed into adulthood

limitations

A database review around an index case. The abstract reports the adult clinical picture; it does not report the accumulating metabolites, so nothing here rests on what backs up behind the missing enzyme.

nutrient_topic

GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

organism

Human

plain_language

When the enzyme that disposes of GABA is missing, most affected adults have epilepsy and psychiatric illness, and the course gets worse.

primary_references

[gb-p26268900] Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. (2015). https://pubmed.ncbi.nlm.nih.gov/26268900/ DOI: 10.1212/wnl.0000000000001906

tissue_or_cell_type

Whole body

GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 157–168

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of a clinical database cohort following identification of a patient diagnosed in the seventh decade · source_derived_draft · unverified_draft

### gb-losing-the-shunt-enzyme Of 95 patients in the database for whom age at diagnosis is recorded there are 40 individuals currently aged 18 years or older and only 3 patients were diagnosed after age 18 years, of 25 adults for whom data are available after age 18, 60% have a history of epilepsy with predominant seizure types being generalized tonic-clonic, absence and myoclonic, EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults, history of psychiatric symptoms was prominent with frequent anxiety, sleep disturbances and obsessive-compulsive disorder, and the illness had a progressive course with fatality at age 63 in the index case. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: When the enzyme that disposes of GABA is missing, most affected adults have epilepsy and psychiatric illness, and the course gets worse. organism: Human tissue_or_cell_type: Whole body experimental_model: Review of a clinical database cohort following identification of a patient diagnosed in the seventh decade limitations: A database review around an index case. The abstract reports the adult clinical picture; it does not report the accumulating metabolites, so nothing here rests on what backs up behind the missing enzyme. exposure: Naturally occurring succinic semialdehyde dehydrogenase deficiency followed into adulthood evidence_span: {"source_cache": "artifacts/gaba-research/26268900.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "23c46d68a8a23c3c561454ff56a07ff6ffa1311207b3fb462b079e21a7f6375c", "start_char": 0, "end_char": 1604, "text_sha256": "23c46d68a8a23c3c561454ff56a07ff6ffa1311207b3fb462b079e21a7f6375c"} [gb-p26268900] Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. (2015). https://pubmed.ncbi.nlm.nih.gov/26268900/ DOI: 10.1212/wnl.0000000000001906

evidence_span

{"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"}

experimental_model

Review of prolyl 4-hydroxylase enzymology and subunit structure

exposure

Hydroxylation of proline in X-Pro-Gly sequences

limitations

An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Mammalian enzyme

plain_language

Making collagen needs oxygen, iron, vitamin C and a Krebs-cycle acid, all four at once.

primary_references

[hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

tissue_or_cell_type

Endoplasmic reticulum

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 855–866

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of prolyl 4-hydroxylase enzymology and subunit structure · source_derived_draft · unverified_draft

### hbot-p4h-cosubstrates Prolyl 4-hydroxylase catalyses formation of 4-hydroxyproline in collagens by hydroxylating proline residues in X-Pro-Gly sequences, and the reaction requires Fe2+, 2-oxoglutarate, O2 and ascorbate, involving oxidative decarboxylation of 2-oxoglutarate. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Making collagen needs oxygen, iron, vitamin C and a Krebs-cycle acid, all four at once. organism: Mammalian enzyme tissue_or_cell_type: Endoplasmic reticulum experimental_model: Review of prolyl 4-hydroxylase enzymology and subunit structure limitations: An authoritative enzymology review rather than a single experiment. It is the source for the cosubstrate list, which is the point at which oxygen, iron and vitamin C meet in collagen synthesis. exposure: Hydroxylation of proline in X-Pro-Gly sequences evidence_span: {"source_cache": "artifacts/hbot-research/2537773.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe", "start_char": 0, "end_char": 2024, "text_sha256": "3fdda2e4cf4392ec7a88b137274cee8f321255473992a2d8df781df12cad6cfe"} [hbot-p2537773] Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. (1989). https://pubmed.ncbi.nlm.nih.gov/2537773/ DOI: 10.1096/fasebj.3.5.2537773

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}]

experimental_model

Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

UQ1/DCIP are assay reagents; the isolated turnover value is not whole-cell ATP production.

nutrient_topic

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

organism

Homo sapiens

plain_language

The intact complex moves electrons from succinate into a quinone carrier.

primary_references

[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

tissue_or_cell_type

HEK293F-derived purified complex II

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 663–674

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft

### b2-met-human-complex-ii-succinate-quinone Purified human complex II coupled succinate oxidation to ubiquinone reduction in a UQ1/DCIP assay, with reported kcat 0.67 +/- 0.02 per second. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The intact complex moves electrons from succinate into a quinone carrier. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: UQ1/DCIP are assay reagents; the isolated turnover value is not whole-cell ATP production. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 2, "char_start": 0, "char_end": 1105, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 3, "char_start": 0, "char_end": 2164, "evidence_access": "full-text"}]

experimental_model

Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays.

exposure

No nutrient intervention; structural or biochemical characterization.

limitations

Structure establishes location, not nutritional sensitivity.

nutrient_topic

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

organism

Homo sapiens

plain_language

The B2-derived cofactor sits in the catalytic SDHA part of complex II.

primary_references

[du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

tissue_or_cell_type

HEK293F-derived purified complex II

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 636–647

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. · source_derived_draft · unverified_draft

### b2-met-human-sdha-fad Cryo-EM of active human complex II resolved FAD within SDHA and located the succinate-fumarate active site between its FAD-binding and capping domains. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B2-derived cofactor sits in the catalytic SDHA part of complex II. organism: Homo sapiens tissue_or_cell_type: HEK293F-derived purified complex II experimental_model: Human complex II purified from HEK293F cells, cryo-EM, EPR and succinate-quinone activity assays. limitations: Structure establishes location, not nutritional sensitivity. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10161127", "locator": "XML .//body//p", "paragraph_index": 3, "char_start": 0, "char_end": 2164, "evidence_access": "full-text"}] [du-2023-human-complex-ii] Structure of the human respiratory complex II (2023). https://pubmed.ncbi.nlm.nih.gov/37098072/ DOI: 10.1073/pnas.2216713120

experimental_model

Human cDNA expression and human tissue activity assays

limitations

Do not generalize full carnitine-synthesis capacity to every tissue.

organism

Homo sapiens

plain_language

BBOX1 completes carnitine synthesis.

primary_references

[vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6

tissue_or_cell_type

Kidney, liver and brain; abundance differs

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 207–216

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA expression and human tissue activity assays · source_derived_draft · unverified_draft

### bbox1-carnitine-formation BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron. Plain language: BBOX1 completes carnitine synthesis. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney, liver and brain; abundance differs experimental_model: Human cDNA expression and human tissue activity assays limitations: Do not generalize full carnitine-synthesis capacity to every tissue. [vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6

experimental_model

Human JMJD2A catalytic-domain structures and methylated peptide assays.

limitations

This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.

organism

Human

plain_language

An iron-dependent enzyme erases a different class of methyl mark.

primary_references

[kdm4a-2006] Structural insights into histone demethylation by JMJD2 family members (2006). https://pubmed.ncbi.nlm.nih.gov/16677698/ DOI: 10.1016/j.cell.2006.04.024 [kdm4a-specificity-2007] Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase (2007). https://pubmed.ncbi.nlm.nih.gov/17589523/ DOI: 10.1038/nsmb1273

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 567–576

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human JMJD2A catalytic-domain structures and methylated peptide assays. · source_derived_draft · unverified_draft

### kdm4a-h3k9-demethylation KDM4A/JMJD2A can convert H3K9me3 to H3K9me2 using Fe(II), oxygen and 2-oxoglutarate. Plain language: An iron-dependent enzyme erases a different class of methyl mark. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human JMJD2A catalytic-domain structures and methylated peptide assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [kdm4a-2006] Structural insights into histone demethylation by JMJD2 family members (2006). https://pubmed.ncbi.nlm.nih.gov/16677698/ DOI: 10.1016/j.cell.2006.04.024 [kdm4a-specificity-2007] Specificity and mechanism of JMJD2A, a trimethyllysine-specific histone demethylase (2007). https://pubmed.ncbi.nlm.nih.gov/17589523/ DOI: 10.1038/nsmb1273

experimental_model

Recombinant human PLOD3 structural and biochemical assays.

limitations

This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome.

organism

Human

plain_language

The collagen enzyme needs an iron-containing catalytic site and reaction partners.

primary_references

[plod3-2018] Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3 (2018). https://www.nature.com/articles/s41467-018-05631-5 DOI: 10.1038/s41467-018-05631-5

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 417–425

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PLOD3 structural and biochemical assays. · source_derived_draft · unverified_draft

### plod3-collagen-hydroxylation PLOD3 hydroxylates peptidyl lysine using Fe(II), 2-oxoglutarate and oxygen. Plain language: The collagen enzyme needs an iron-containing catalytic site and reaction partners. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Recombinant human PLOD3 structural and biochemical assays. limitations: This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [plod3-2018] Molecular architecture of the multifunctional collagen lysyl hydroxylase and glycosyltransferase LH3 (2018). https://www.nature.com/articles/s41467-018-05631-5 DOI: 10.1038/s41467-018-05631-5

experimental_model

Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays

limitations

The substrate is free trimethyllysine after proteolysis, not ordinary free lysine.

organism

Homo sapiens

plain_language

TMLHE begins conversion of released trimethyllysine toward carnitine.

primary_references

[lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A

tissue_or_cell_type

Mitochondrial carnitine-biosynthesis step

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 166–175

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays · source_derived_draft · unverified_draft

### tmlhe-hydroxylation Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation. Plain language: TMLHE begins conversion of released trimethyllysine toward carnitine. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial carnitine-biosynthesis step experimental_model: Recombinant human TMLH, synthetic standards and NMR; Recombinant human TMLH and substrate analogue assays limitations: The substrate is free trimethyllysine after proteolysis, not ordinary free lysine. [lesniak2017] Human carnitine biosynthesis proceeds via (2S,3S)-3-hydroxy-Nε-trimethyllysine (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5644716/ DOI: 10.1039/C6CC08381A [tmlh2016scope] Substrate scope for trimethyllysine hydroxylase catalysis (2016). https://pubs.rsc.org/en/content/articlehtml/2016/cc/c6cc07845a DOI: 10.1039/C6CC07845A

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

cross_nutrient

Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.

experimental_model

Purified chick prolyl and partially purified lysyl collagen hydroxylases

exposure

Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays.

limitations

This statement concerns coupled turnover; it must not be transferred to copper monooxygenases.

nutrient_topic

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

organism

Gallus gallus

plain_language

Vitamin C is not a one-for-one consumed ingredient in every successful collagen hydroxylation.

primary_references

[myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

tissue_or_cell_type

Chick embryo enzyme preparations

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 585–596

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick prolyl and partially purified lysyl collagen hydroxylases · source_derived_draft · unverified_draft

### vc-enzyme-coupled-ascorbate-use In chick collagen hydroxylase assays, complete proline hydroxylation was coupled to 2-oxoglutarate decarboxylation while ascorbate was not consumed in most catalytic cycles. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C is not a one-for-one consumed ingredient in every successful collagen hydroxylation. organism: Gallus gallus tissue_or_cell_type: Chick embryo enzyme preparations experimental_model: Purified chick prolyl and partially purified lysyl collagen hydroxylases limitations: This statement concerns coupled turnover; it must not be transferred to copper monooxygenases. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: Peptide substrate present or absent; uncoupled 2-oxoglutarate decarboxylation assays. [myllyla1984] Ascorbate is consumed stoichiometrically in the uncoupled reactions catalyzed by prolyl 4-hydroxylase and lysyl hydroxylase. (1984). https://pubmed.ncbi.nlm.nih.gov/6325436/ DOI: 10.1016/s0021-9258(18)91023-9

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human 143B and other cell models; live aspartate biosensor and time-resolved metabolomics.

limitations

Responses are time- and model-dependent; later adaptation does not make the early block disappear.

nutrient_topic

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

plain_language

A restored metabolite concentration did not show that the cell could use it normally.

primary_references

Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 202–208

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 143B and other cell models; live aspartate biosensor and time-resolved metabolomics. · source_derived_draft · unverified_draft

## l-aspartate-sdh-aspartate-rebound A restored metabolite concentration did not show that the cell could use it normally. SDH inhibition produced early aspartate depletion followed by a rebound, while proliferation remained impaired over the compared interval. Model: Human 143B and other cell models; live aspartate biosensor and time-resolved metabolomics. Limitations: Responses are time- and model-dependent; later adaptation does not make the early block disappear. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cell genetic/pharmacological SDH perturbations; nucleotide and replication readouts.

limitations

Not a clinical treatment recommendation or proof that extra aspartate universally overcomes the competitive block.

nutrient_topic

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

plain_language

The effect propagated from metabolism into DNA replication control.

primary_references

Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 218–224

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell genetic/pharmacological SDH perturbations; nucleotide and replication readouts. · source_derived_draft · unverified_draft

## l-aspartate-sdh-pyrimidine-stress The effect propagated from metabolism into DNA replication control. SDH loss increased succinate, impaired aspartate entry into pyrimidine synthesis and produced nucleotide insufficiency with replication stress and increased ATR-inhibitor sensitivity. Model: Human cell genetic/pharmacological SDH perturbations; nucleotide and replication readouts. Limitations: Not a clinical treatment recommendation or proof that extra aspartate universally overcomes the competitive block. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w