Carbon dioxide

evidence_span

{"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"}

experimental_model

Cryo-EM, mutagenesis and molecular dynamics

exposure

GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin

limitations

The carbon-capture/proton-transfer sequence is the authors' structural mechanistic model, not a measured human dietary response or an established bicarbonate-supplement interaction.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human GGCX

plain_language

The added chemical group comes from carbon dioxide; vitamin K supports the reaction rather than supplying the carbon.

primary_references

[k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3

tissue_or_cell_type

Substrate recognition and carbon-dioxide capture

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 422–433

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, mutagenesis and molecular dynamics · source_derived_draft · unverified_draft

### k2-ggcx-carbon-capture Cryo-EM structures and biochemical analyses supported a proposed bicarbonate-mediated carbon-dioxide capture model for GGCX. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The added chemical group comes from carbon dioxide; vitamin K supports the reaction rather than supplying the carbon. organism: Human GGCX tissue_or_cell_type: Substrate recognition and carbon-dioxide capture experimental_model: Cryo-EM, mutagenesis and molecular dynamics limitations: The carbon-capture/proton-transfer sequence is the authors' structural mechanistic model, not a measured human dietary response or an established bicarbonate-supplement interaction. exposure: GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin evidence_span: {"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"} [k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3

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

cross_nutrient

PLP chemistry connects with the lipoyl component of glycine cleavage.

experimental_model

Purified chicken liver mitochondrial P-protein

limitations

Free lipoic acid assay; not evidence that supplements replace the intact cleavage system.

nutrient_topic

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

organism

Gallus gallus

plain_language

B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners.

primary_references

[b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5

tissue_or_cell_type

Chicken liver mitochondrial protein

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 659–669

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chicken liver mitochondrial P-protein · source_derived_draft · unverified_draft

### b6-met-chicken-gldc-decarboxylation Chicken P-protein alone catalyzed very slow glycine decarboxylation; added lipoic acid stimulated the measured decarboxylation at least 100-fold. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent glycine cleavage also depends on its lipoyl-linked reaction partners. organism: Gallus gallus tissue_or_cell_type: Chicken liver mitochondrial protein experimental_model: Purified chicken liver mitochondrial P-protein limitations: Free lipoic acid assay; not evidence that supplements replace the intact cleavage system. cross_nutrient: PLP chemistry connects with the lipoyl component of glycine cleavage. [b6-gldc-1980] The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria. (1980). https://pubmed.ncbi.nlm.nih.gov/7440562/ DOI: 10.1016/s0021-9258(19)70183-5

cross_nutrient

Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay

exposure

50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions.

limitations

In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Bos taurus osteocalcin; liver-derived enzyme preparation

plain_language

Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction.

primary_references

[vdm-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066

tissue_or_cell_type

Cell-free enzyme assay

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 889–903

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay · source_derived_draft · unverified_draft

### vdm-vitamin-k-carboxylase-modifies-osteocalcin A concentrated vitamin K-dependent carboxylase preparation converted glutamate residues of decarboxylated bovine osteocalcin into gamma-carboxyglutamate in vitro. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Osteocalcin needs a separate vitamin K-dependent protein-modification step; making more osteocalcin is not the same reaction. organism: Bos taurus osteocalcin; liver-derived enzyme preparation tissue_or_cell_type: Cell-free enzyme assay experimental_model: Microsomal vitamin K-dependent carboxylase enriched about 100-fold; bovine osteocalcin substrate and CO2-incorporation assay limitations: In-vitro modification of a defined substrate; no D-plus-K supplementation regimen, K2-specific necessity, improved fracture outcome or obligatory supplement pairing was tested. exposure: 50 mM bicarbonate, excess enriched carboxylase and limiting decarboxylated osteocalcin; vitamin K-dependent reaction conditions. cross_nutrient: Vitamin D regulates osteocalcin expression in specified models; vitamin K-dependent carboxylation modifies its protein product through a distinct enzyme reaction. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-soute1987] Vitamin K-dependent carboxylase: increased efficiency of the carboxylation reaction. (1987). https://pubmed.ncbi.nlm.nih.gov/3495900/ DOI: 10.1055/s-0038-1651066

evidence

[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human OGDH circular dichroism and related spectroscopy.

limitations

Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli.

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

At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants.

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 E1

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 842–853

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OGDH circular dichroism and related spectroscopy. · source_derived_draft · unverified_draft

### b1-ogdh-thdp-enamine-chemistry Human recombinant OGDH reacted with 2-oxoglutarate to produce spectroscopic signals supporting a ThDP-bound post-decarboxylation enamine. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants. organism: Homo sapiens tissue_or_cell_type: Purified E1 experimental_model: Human OGDH circular dichroism and related spectroscopy. limitations: Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] 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

[{"paper_key": "seifert-2006-pdh-catalysis", "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 E1; transient kinetics.

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

Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made.

primary_references

[seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l

tissue_or_cell_type

Purified mitochondrial enzyme

Thiamine: 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 · Recombinant human E1; transient kinetics. · source_derived_draft · unverified_draft

### b1-pdh-pyruvate-covalent-decarboxylation Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made. organism: Homo sapiens tissue_or_cell_type: Purified mitochondrial enzyme experimental_model: Recombinant human E1; transient kinetics. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "seifert-2006-pdh-catalysis", "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."}] nutrient: Thiamine (vitamin B1) [seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l

cross_nutrient

false

experimental_model

Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology

exposure

Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk.

limitations

Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations.

nutrient_topic

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

organism

Homo sapiens

plain_language

Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate.

primary_references

[zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9

tissue_or_cell_type

Human saliva and breast milk; purified enzyme assay

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 664–675

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology · source_derived_draft · unverified_draft

### zinc-enz-ca6-hydration Purified human salivary and milk CA6 catalyzed CO2 hydration, with reported kcat values of 3.3×10^5 and 2.3×10^5 s−1, respectively. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Secreted CA6 accelerates conversion of carbon dioxide and water into bicarbonate. organism: Homo sapiens tissue_or_cell_type: Human saliva and breast milk; purified enzyme assay experimental_model: Human CA6 purified from pooled saliva or breast milk; stopped-flow enzymology limitations: Protein kinetic measurements; no test of dietary zinc treatment or infant health outcomes. Table values characterize the isolated preparations. exposure: Stopped-flow CO2 hydration assay of proteins purified from pooled human saliva and milk. cross_nutrient: false [zinc-enz-ca6-2022] Biochemical and Biophysical Characterization of Carbonic Anhydrase VI from Human Milk and Saliva. (2022). https://pubmed.ncbi.nlm.nih.gov/35947329/ DOI: 10.1007/s10930-022-10070-9

experimental_model

E. coli inducible lysine decarboxylase structural and acid-stress experiments.

limitations

Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism.

organism

Escherichia coli

plain_language

Some bacteria use lysine to buffer acidic conditions.

primary_references

[cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

tissue_or_cell_type

Not specified as a whole tissue; see experimental model.

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 618–626

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · E. coli inducible lysine decarboxylase structural and acid-stress experiments. · source_derived_draft · unverified_draft

### bacterial-cada-decarboxylation E. coli CadA converts lysine to cadaverine and CO2 while consuming a proton during acid stress. Plain language: Some bacteria use lysine to buffer acidic conditions. Condition category: normal organism: Escherichia coli tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: E. coli inducible lysine decarboxylase structural and acid-stress experiments. limitations: Bacterial pathway. Cadaverine exposure or health effects in a human cannot be inferred from this culture mechanism. [cada-2011] Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase (2011). https://pubmed.ncbi.nlm.nih.gov/21278708/ DOI: 10.1038/emboj.2011.5

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 GCDH crystallography and substrate-mechanism analysis

limitations

The downstream shared ECHS1/HADH/ACAT1 reactions are separate records; these individual enzyme assays do not measure the full lysine-derived flux in a person.

organism

Homo sapiens

plain_language

GCDH shortens the lysine-derived carbon chain.

primary_references

[fu2004] Crystal Structures of Human Glutaryl-CoA Dehydrogenase with and without an Alternate Substrate: Structural Bases of Dehydrogenation and Decarboxylation Reactions (2004). https://pubs.acs.org/doi/10.1021/bi049290c DOI: 10.1021/bi049290c

tissue_or_cell_type

Mitochondrial matrix

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 136–144

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GCDH crystallography and substrate-mechanism analysis · source_derived_draft · unverified_draft

### gcdh-crotonyl-coa FAD-containing human GCDH dehydrogenates glutaryl-CoA through glutaconyl-CoA and decarboxylates it to crotonyl-CoA. Plain language: GCDH shortens the lysine-derived carbon chain. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Human GCDH crystallography and substrate-mechanism analysis limitations: The downstream shared ECHS1/HADH/ACAT1 reactions are separate records; these individual enzyme assays do not measure the full lysine-derived flux in a person. [fu2004] Crystal Structures of Human Glutaryl-CoA Dehydrogenase with and without an Alternate Substrate: Structural Bases of Dehydrogenation and Decarboxylation Reactions (2004). https://pubs.acs.org/doi/10.1021/bi049290c DOI: 10.1021/bi049290c

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 DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation

limitations

DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction.

organism

Homo sapiens

plain_language

A three-enzyme complex converts the carbon skeleton into glutaryl-CoA.

primary_references

[bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

tissue_or_cell_type

Mitochondrial matrix

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 125–134

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation · source_derived_draft · unverified_draft

### oxoadipate-dehydrogenase-complex DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation. Plain language: A three-enzyme complex converts the carbon skeleton into glutaryl-CoA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation limitations: DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction. [bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

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

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

cross_nutrient

CoA maturation enables the folate-to-NADPH reaction.

experimental_model

Recombinant enzyme activation assay

exposure

Assay conditions described in the linked primary study.

limitations

Figure 5 used stable dideazafolate analogue rather than physiological folate.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Homo sapiens

plain_language

The installed arm enables oxidation of folate-bound carbon.

primary_references

[strickland-2011] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase (2011). https://pubmed.ncbi.nlm.nih.gov/21238436/ DOI: 10.1016/j.cbi.2011.01.008

tissue_or_cell_type

Cell-free

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1059–1070

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

### aldh1l2-activation-folate-oxidation Phosphopantetheinylation restored recombinant ALDH1L2 folate dehydrogenase activity with NADPH formation. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The installed arm enables oxidation of folate-bound carbon. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Recombinant enzyme activation assay limitations: Figure 5 used stable dideazafolate analogue rather than physiological folate. exposure: Assay conditions described in the linked primary study. cross_nutrient: CoA maturation enables the folate-to-NADPH reaction. [strickland-2011] Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase (2011). https://pubmed.ncbi.nlm.nih.gov/21238436/ DOI: 10.1016/j.cbi.2011.01.008