Nutrient chapter

L-Lysine

Free L-enantiomer of lysine, an indispensable proteinogenic amino acid. Separate from protein-bound lysine residues, D-lysine and polylysine.

80 recorded mechanisms · 17 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Human CAT1 transports L-lysine across the plasma membrane.
CAT1 / SLC7A1 → L-Lysine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human CAT1 expressed in Xenopus oocytes
limitations
Transporter expression assay; the relative contribution varies by tissue.
organism
Homo sapiens
plain_language
CAT1 moves free lysine across cell membranes.
primary_references
[furesz2002] Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast surface membranes. (2002). https://pubmed.ncbi.nlm.nih.gov/12202949/ DOI: 10.1007/s00232-002-1001-0
tissue_or_cell_type
Plasma membrane; compared with placental trophoblast membranes
transport_effect
depends The record names the membrane lysine crosses and not which way it crosses it.
transport_pool
the cytosol across the plasma membrane The record names the membrane lysine crosses and not which way it crosses it.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 14–22
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CAT1 expressed in Xenopus oocytes · source_derived_draft · unverified_draft
### cat1-lysine-transport Human CAT1 transports L-lysine across the plasma membrane. Plain language: CAT1 moves free lysine across cell membranes. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Plasma membrane; compared with placental trophoblast membranes experimental_model: Human CAT1 expressed in Xenopus oocytes limitations: Transporter expression assay; the relative contribution varies by tissue. [furesz2002] Lysine uptake by cloned hCAT-2B: comparison with hCAT-1 and with trophoblast surface membranes. (2002). https://pubmed.ncbi.nlm.nih.gov/12202949/ DOI: 10.1007/s00232-002-1001-0
Complete structured claim and evidence
SLC7A9 associated with SLC3A1 mediates sodium-independent lysine exchange at the apical epithelial membrane.
b0,+AT-rBAT complex → L-Lysine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human/mouse cloning, Xenopus transport and renal localization
limitations
Leucine is an example exchange substrate, not the obligatory unique counter-substrate.
organism
Human and mouse proteins; Xenopus expression system
plain_language
This transporter admits lysine at the gut or kidney lumen-facing surface.
primary_references
[pfeiffer1999b0] Luminal Heterodimeric Amino Acid Transporter Defective in Cystinuria (1999). https://pmc.ncbi.nlm.nih.gov/articles/PMC25748/ DOI: 10.1091/mbc.10.12.4135
tissue_or_cell_type
Renal proximal-tubule brush border; intestinal apical context
transport_effect
depends The record names sodium-independent lysine exchange and not which way lysine moves in it.
transport_pool
the enterocyte interior across the apical membrane The record names sodium-independent lysine exchange and not which way lysine moves in it.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 24–32
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human/mouse cloning, Xenopus transport and renal localization · source_derived_draft · unverified_draft
### apical-lysine-exchange SLC7A9 associated with SLC3A1 mediates sodium-independent lysine exchange at the apical epithelial membrane. Plain language: This transporter admits lysine at the gut or kidney lumen-facing surface. Condition category: normal organism: Human and mouse proteins; Xenopus expression system tissue_or_cell_type: Renal proximal-tubule brush border; intestinal apical context experimental_model: Human/mouse cloning, Xenopus transport and renal localization limitations: Leucine is an example exchange substrate, not the obligatory unique counter-substrate. [pfeiffer1999b0] Luminal Heterodimeric Amino Acid Transporter Defective in Cystinuria (1999). https://pmc.ncbi.nlm.nih.gov/articles/PMC25748/ DOI: 10.1091/mbc.10.12.4135
Complete structured claim and evidence
SLC7A7-SLC3A2 exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids with sodium.
y+LAT1-4F2hc complex → L-Lysine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human/mouse heterodimer expression and exchange assays
limitations
Neutral-substrate transport is sodium-dependent; lysine binding itself should not be mislabeled a sodium cotransport step.
organism
Homo sapiens
plain_language
This route helps lysine leave epithelial cells toward blood.
primary_references
[pfeiffer1999yl] Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family. (1999). https://pubmed.ncbi.nlm.nih.gov/9878049/ DOI: 10.1093/emboj/18.1.49
tissue_or_cell_type
Basolateral intestinal and renal epithelial membranes
transport_effect
lowers Exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids, so lysine leaves the cell.
transport_pool
the enterocyte interior Exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids, so lysine leaves the cell.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 34–42
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human/mouse heterodimer expression and exchange assays · source_derived_draft · unverified_draft
### basolateral-lysine-exchange SLC7A7-SLC3A2 exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids with sodium. Plain language: This route helps lysine leave epithelial cells toward blood. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Basolateral intestinal and renal epithelial membranes experimental_model: Human/mouse heterodimer expression and exchange assays limitations: Neutral-substrate transport is sodium-dependent; lysine binding itself should not be mislabeled a sodium cotransport step. [pfeiffer1999yl] Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family. (1999). https://pubmed.ncbi.nlm.nih.gov/9878049/ DOI: 10.1093/emboj/18.1.49
Complete structured claim and evidence
Reconstituted human SLC25A29 transports lysine by uniport and exchange, supporting lysine entry into the mitochondrial matrix.
SLC25A29 → L-Lysine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified recombinant carrier reconstituted in liposomes
limitations
Physiological import role is inferred from transport properties and localization; not a carnitine transporter.
organism
Homo sapiens
plain_language
SLC25A29 gives lysine access to mitochondrial metabolism.
primary_references
[porcelli2014] The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4036346/ DOI: 10.1074/jbc.M114.547448
tissue_or_cell_type
Inner mitochondrial membrane
transport_effect
raises Uniport and exchange supporting lysine entry into the matrix.
transport_pool
the mitochondrial matrix Uniport and exchange supporting lysine entry into the matrix.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 44–52
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant carrier reconstituted in liposomes · source_derived_draft · unverified_draft
### mitochondrial-lysine-transport Reconstituted human SLC25A29 transports lysine by uniport and exchange, supporting lysine entry into the mitochondrial matrix. Plain language: SLC25A29 gives lysine access to mitochondrial metabolism. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Purified recombinant carrier reconstituted in liposomes limitations: Physiological import role is inferred from transport properties and localization; not a carnitine transporter. [porcelli2014] The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4036346/ DOI: 10.1074/jbc.M114.547448
Complete structured claim and evidence
KARS1 activates lysine with ATP, forming enzyme-bound lysyl-adenylate and releasing pyrophosphate.
L-Lysine → Lysyl-adenylate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human LysRS cryo-EM and aminoacylation assays
limitations
The structural experiment used tRNA-Lys3; KARS1 is not the leucyl-tRNA synthetase LARS1.
organism
Homo sapiens
plain_language
ATP activates lysine before it is attached to its carrier RNA.
primary_references
[devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114
tissue_or_cell_type
Cytosolic tRNA charging
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 54–62
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human LysRS cryo-EM and aminoacylation assays · source_derived_draft · unverified_draft
### lysine-adenylation KARS1 activates lysine with ATP, forming enzyme-bound lysyl-adenylate and releasing pyrophosphate. Plain language: ATP activates lysine before it is attached to its carrier RNA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic tRNA charging experimental_model: Human LysRS cryo-EM and aminoacylation assays limitations: The structural experiment used tRNA-Lys3; KARS1 is not the leucyl-tRNA synthetase LARS1. [devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114
Complete structured claim and evidence
After pyrophosphate release, KARS1 transfers activated lysine to the tRNA-Lys 3-prime end, forming lysyl-tRNA and AMP.
Lysyl-adenylate → Lysyl-tRNA-Lys source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human LysRS-tRNA-Lys3 structural and enzyme assays
limitations
This is tRNA charging; subsequent ribosomal peptide-bond formation is a distinct step.
organism
Homo sapiens
plain_language
Charged tRNA supplies lysine for protein synthesis.
primary_references
[devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114
tissue_or_cell_type
Cytosolic translation machinery
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 64–72
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human LysRS-tRNA-Lys3 structural and enzyme assays · source_derived_draft · unverified_draft
### lysyl-trna-formation After pyrophosphate release, KARS1 transfers activated lysine to the tRNA-Lys 3-prime end, forming lysyl-tRNA and AMP. Plain language: Charged tRNA supplies lysine for protein synthesis. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic translation machinery experimental_model: Human LysRS-tRNA-Lys3 structural and enzyme assays limitations: This is tRNA charging; subsequent ribosomal peptide-bond formation is a distinct step. [devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114
Complete structured claim and evidence
The AASS reductase domain condenses lysine with 2-oxoglutarate using NADPH to form saccharopine.
L-Lysine → Saccharopine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human AASS and isolated reductase domain
limitations
Reaction reversibility in vitro does not imply appreciable human lysine biosynthesis.
organism
Homo sapiens
plain_language
AASS starts the main lysine breakdown route.
primary_references
[leandro2022] Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1 (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9490328/ DOI: 10.1098/rsob.220179
tissue_or_cell_type
Mitochondrial matrix
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 74–82
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human AASS and isolated reductase domain · source_derived_draft · unverified_draft
### aass-reductase The AASS reductase domain condenses lysine with 2-oxoglutarate using NADPH to form saccharopine. Plain language: AASS starts the main lysine breakdown route. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human AASS and isolated reductase domain limitations: Reaction reversibility in vitro does not imply appreciable human lysine biosynthesis. [leandro2022] Characterization and structure of the human lysine-2-oxoglutarate reductase domain, a novel therapeutic target for treatment of glutaric aciduria type 1 (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9490328/ DOI: 10.1098/rsob.220179
Complete structured claim and evidence
The AASS dehydrogenase domain oxidatively cleaves saccharopine, producing alpha-aminoadipate semialdehyde and glutamate with NAD+ reduction.
Saccharopine → alpha-Aminoadipate semialdehyde source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human AASS cloning, localization and familial hyperlysinemia genetics
limitations
Biochemical capacity does not quantify flux in every human tissue.
organism
Homo sapiens
plain_language
The second AASS activity opens the next lysine breakdown step.
primary_references
[sacksteder2000] Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia (2000). https://pmc.ncbi.nlm.nih.gov/articles/PMC1378037/ DOI: 10.1086/302919
tissue_or_cell_type
Mitochondrial matrix
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 84–92
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human AASS cloning, localization and familial hyperlysinemia genetics · source_derived_draft · unverified_draft
### aass-saccharopine-dehydrogenase The AASS dehydrogenase domain oxidatively cleaves saccharopine, producing alpha-aminoadipate semialdehyde and glutamate with NAD+ reduction. Plain language: The second AASS activity opens the next lysine breakdown step. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Human AASS cloning, localization and familial hyperlysinemia genetics limitations: Biochemical capacity does not quantify flux in every human tissue. [sacksteder2000] Identification of the alpha-aminoadipic semialdehyde synthase gene, which is defective in familial hyperlysinemia (2000). https://pmc.ncbi.nlm.nih.gov/articles/PMC1378037/ DOI: 10.1086/302919
Complete structured claim and evidence
Alpha-aminoadipate semialdehyde interconverts with its cyclic Schiff base P6C.
alpha-Aminoadipate semialdehyde → Delta1-piperideine-6-carboxylate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Biochemical characterization
limitations
The two chemical species are separate entities connected by equilibrium.
organism
Homo sapiens
plain_language
One intermediate exists in open-chain and ring forms.
primary_references
[mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
tissue_or_cell_type
Lysine-catabolizing compartments and body fluids
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 94–102
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical characterization · source_derived_draft · unverified_draft
### aasa-p6c-equilibrium Alpha-aminoadipate semialdehyde interconverts with its cyclic Schiff base P6C. Plain language: One intermediate exists in open-chain and ring forms. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Lysine-catabolizing compartments and body fluids experimental_model: Biochemical characterization limitations: The two chemical species are separate entities connected by equilibrium. [mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
Complete structured claim and evidence
ALDH7A1 oxidizes alpha-aminoadipate semialdehyde to alpha-aminoadipate using NAD+.
alpha-Aminoadipate semialdehyde → L-alpha-Aminoadipate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human ALDH7A1 biochemical and genetic study
limitations
Compartmental isoform distribution is not resolved by this claim.
organism
Homo sapiens
plain_language
Antiquitin clears the aldehyde intermediate.
primary_references
[luo2015] Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1 (2015). https://pubmed.ncbi.nlm.nih.gov/26260980/ DOI: 10.1021/acs.biochem.5b00754
tissue_or_cell_type
Lysine-catabolizing tissues
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 104–112
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ALDH7A1 biochemical and genetic study · source_derived_draft · unverified_draft
### aldh7a1-oxidation ALDH7A1 oxidizes alpha-aminoadipate semialdehyde to alpha-aminoadipate using NAD+. Plain language: Antiquitin clears the aldehyde intermediate. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Lysine-catabolizing tissues experimental_model: Human ALDH7A1 biochemical and genetic study limitations: Compartmental isoform distribution is not resolved by this claim. [luo2015] Structural Basis of Substrate Recognition by Aldehyde Dehydrogenase 7A1 (2015). https://pubmed.ncbi.nlm.nih.gov/26260980/ DOI: 10.1021/acs.biochem.5b00754
Complete structured claim and evidence
PLP-dependent AADAT transfers the amino group from aminoadipate to 2-oxoglutarate, generating 2-oxoadipate and glutamate.
L-alpha-Aminoadipate → 2-Oxoadipate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography
limitations
AADAT also accepts other substrates; substrate breadth is not lysine-specific regulation.
organism
Homo sapiens
plain_language
AADAT removes the remaining amino group.
primary_references
[goh2002] Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). (2002). https://pubmed.ncbi.nlm.nih.gov/12126930/ DOI: 10.1016/S1096-7192(02)00037-9 [han2008] Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2559858/ DOI: 10.1042/BSR20080085
tissue_or_cell_type
Mitochondrial lysine catabolism; human expression highest in liver in cloning study
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 114–123
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography · source_derived_draft · unverified_draft
### aadat-transamination PLP-dependent AADAT transfers the amino group from aminoadipate to 2-oxoglutarate, generating 2-oxoadipate and glutamate. Plain language: AADAT removes the remaining amino group. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial lysine catabolism; human expression highest in liver in cloning study experimental_model: Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography limitations: AADAT also accepts other substrates; substrate breadth is not lysine-specific regulation. [goh2002] Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). (2002). https://pubmed.ncbi.nlm.nih.gov/12126930/ DOI: 10.1016/S1096-7192(02)00037-9 [han2008] Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2559858/ DOI: 10.1042/BSR20080085
Complete structured claim and evidence
DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation.
2-Oxoadipate → Glutaryl-CoA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
FAD-containing human GCDH dehydrogenates glutaryl-CoA through glutaconyl-CoA and decarboxylates it to crotonyl-CoA.
Glutaryl-CoA → Crotonyl-CoA source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Human peroxisomal PIPOX oxidizes L-pipecolate to P6C.
L-Pipecolate → Delta1-piperideine-6-carboxylate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human cDNA cloning and expressed enzyme
limitations
Enzyme capability does not establish that this route predominates in human brain; see conflict.
organism
Homo sapiens
plain_language
Pipecolate can join the common lysine breakdown route.
primary_references
[ijlst2000] Molecular cloning and expression of human L-pipecolate oxidase (2000). https://pubmed.ncbi.nlm.nih.gov/10772957/ DOI: 10.1006/bbrc.2000.2575
tissue_or_cell_type
Peroxisomes
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 146–154
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA cloning and expressed enzyme · source_derived_draft · unverified_draft
### pipox-pipecolate-oxidation Human peroxisomal PIPOX oxidizes L-pipecolate to P6C. Plain language: Pipecolate can join the common lysine breakdown route. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Peroxisomes experimental_model: Human cDNA cloning and expressed enzyme limitations: Enzyme capability does not establish that this route predominates in human brain; see conflict. [ijlst2000] Molecular cloning and expression of human L-pipecolate oxidase (2000). https://pubmed.ncbi.nlm.nih.gov/10772957/ DOI: 10.1006/bbrc.2000.2575
Complete structured claim and evidence
Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis.
Protein-bound N-epsilon-trimethyllysine residues → Free N-epsilon-trimethyl-L-lysine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Radiolabeled asialofetuin metabolism in rats and perfused rat liver
limitations
Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge.
organism
Rattus norvegicus
plain_language
Protein breakdown releases the modified lysine used to make carnitine.
primary_references
[labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
tissue_or_cell_type
Liver lysosomes and downstream metabolism
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 156–164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiolabeled asialofetuin metabolism in rats and perfused rat liver · source_derived_draft · unverified_draft
### protein-tml-release Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis. Plain language: Protein breakdown releases the modified lysine used to make carnitine. Condition category: normal organism: Rattus norvegicus tissue_or_cell_type: Liver lysosomes and downstream metabolism experimental_model: Radiolabeled asialofetuin metabolism in rats and perfused rat liver limitations: Direct tracer evidence is rat; do not replace this with a direct free-lysine-to-carnitine edge. [labadie1976] Hepatic synthesis of carnitine from protein-bound trimethyl-lysine. Lysosomal digestion of methyl-lysine-labelled asialo-fetuin (1976). https://pubmed.ncbi.nlm.nih.gov/64247/ DOI: 10.1042/bj1600085
Complete structured claim and evidence
Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.
Free N-epsilon-trimethyl-L-lysine → (2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine.
(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human enzyme; NMR and coupled activity assays
limitations
Whole-body flux contribution remains unquantified.
organism
Homo sapiens
plain_language
SHMT1 can perform the second carnitine-synthesis reaction.
primary_references
[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
tissue_or_cell_type
Cytosolic enzyme tested in vitro
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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme; NMR and coupled activity assays · source_derived_draft · unverified_draft
### shmt1-html-cleavage Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine. Plain language: SHMT1 can perform the second carnitine-synthesis reaction. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic enzyme tested in vitro experimental_model: Purified human enzyme; NMR and coupled activity assays limitations: Whole-body flux contribution remains unquantified. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
Complete structured claim and evidence
Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1.
(2S,3S)-3-Hydroxy-N-epsilon-trimethyllysine → 4-Trimethylaminobutyraldehyde source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human enzyme kinetic assay
limitations
Mouse Tha1 specialization should not be assigned to a human THA1 enzyme.
organism
Homo sapiens
plain_language
SHMT2 provides another demonstrated aldolase activity.
primary_references
[osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
tissue_or_cell_type
Mitochondrial enzyme tested in vitro
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 187–195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human enzyme kinetic assay · source_derived_draft · unverified_draft
### shmt2-html-cleavage Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1. Plain language: SHMT2 provides another demonstrated aldolase activity. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial enzyme tested in vitro experimental_model: Purified human enzyme kinetic assay limitations: Mouse Tha1 specialization should not be assigned to a human THA1 enzyme. [osmes2024] One substrate many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse (2024). https://www.nature.com/articles/s41467-024-47466-3 DOI: 10.1038/s41467-024-47466-3
Complete structured claim and evidence
Human ALDH9A1 oxidizes trimethylaminobutyraldehyde to gamma-butyrobetaine using NAD+.
4-Trimethylaminobutyraldehyde → gamma-Butyrobetaine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Rat enzyme purification and recombinant human ALDH9 comparison
limitations
ALDH9A1 has additional aldehyde substrates.
organism
Homo sapiens
plain_language
An aldehyde is converted into the immediate carnitine precursor.
primary_references
[vaz2000] Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis (2000). https://pubmed.ncbi.nlm.nih.gov/10702312/ DOI: 10.1074/jbc.275.10.7390
tissue_or_cell_type
Cytosolic carnitine-biosynthesis reaction
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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat enzyme purification and recombinant human ALDH9 comparison · source_derived_draft · unverified_draft
### aldh9a1-tmaba-oxidation Human ALDH9A1 oxidizes trimethylaminobutyraldehyde to gamma-butyrobetaine using NAD+. Plain language: An aldehyde is converted into the immediate carnitine precursor. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic carnitine-biosynthesis reaction experimental_model: Rat enzyme purification and recombinant human ALDH9 comparison limitations: ALDH9A1 has additional aldehyde substrates. [vaz2000] Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis (2000). https://pubmed.ncbi.nlm.nih.gov/10702312/ DOI: 10.1074/jbc.275.10.7390
Complete structured claim and evidence
BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron.
gamma-Butyrobetaine → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
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
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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
Complete structured claim and evidence
Pathogenic SLC7A7 variants impair epithelial dibasic-amino-acid transport in lysinuric protein intolerance.
y+LAT1 / SLC7A7 → Basolateral lysine export source_derived_draftungraded
Experimental context and source evidence
affected_machinery
SLC7A7-containing transporter
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine deficiency
experimental_model
Human inherited disease genetics and transport characterization
limitations
A multiamino-acid transport disorder; systemic manifestations are not attributable solely to dietary lysine shortage.
organism
Homo sapiens
plain_language
A transport defect can limit lysine delivery despite its presence in food.
primary_references
[torrents1999] Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene (1999). https://www.nature.com/articles/ng0399_293 DOI: 10.1038/6809
tissue_or_cell_type
Intestinal and renal epithelial basolateral membranes
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human inherited disease genetics and transport characterization · source_derived_draft · unverified_draft
### slc7a7-lpi Pathogenic SLC7A7 variants impair epithelial dibasic-amino-acid transport in lysinuric protein intolerance. Plain language: A transport defect can limit lysine delivery despite its presence in food. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Intestinal and renal epithelial basolateral membranes experimental_model: Human inherited disease genetics and transport characterization limitations: A multiamino-acid transport disorder; systemic manifestations are not attributable solely to dietary lysine shortage. affected_machinery: SLC7A7-containing transporter deficiency_not_equivalent: Dietary lysine deficiency [torrents1999] Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene (1999). https://www.nature.com/articles/ng0399_293 DOI: 10.1038/6809
Complete structured claim and evidence
Selective AASS saccharopine-dehydrogenase impairment while reductase activity persists causes saccharopine accumulation.
AASS → Saccharopine source_derived_draftungraded
Experimental context and source evidence
affected_machinery
AASS saccharopine dehydrogenase
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine deficiency or complete AASS knockout
experimental_model
AASS-domain mutant worms and engineered mice
limitations
Selective downstream-domain failure differs from complete AASS loss.
organism
Caenorhabditis elegans and Mus musculus
plain_language
Saccharopine builds up when its production continues but its removal fails.
primary_references
[zhou2019] The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6363459/ DOI: 10.1083/jcb.201807204
tissue_or_cell_type
Worm hypodermis and mouse liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 230–240
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · AASS-domain mutant worms and engineered mice · source_derived_draft · unverified_draft
### aass-sdh-saccharopine-accumulation Selective AASS saccharopine-dehydrogenase impairment while reductase activity persists causes saccharopine accumulation. Plain language: Saccharopine builds up when its production continues but its removal fails. Condition category: machinery_impairment organism: Caenorhabditis elegans and Mus musculus tissue_or_cell_type: Worm hypodermis and mouse liver experimental_model: AASS-domain mutant worms and engineered mice limitations: Selective downstream-domain failure differs from complete AASS loss. affected_machinery: AASS saccharopine dehydrogenase deficiency_not_equivalent: Dietary lysine deficiency or complete AASS knockout [zhou2019] The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6363459/ DOI: 10.1083/jcb.201807204
Complete structured claim and evidence
Excess saccharopine disrupts mitochondrial morphology and function in AASS-domain mutant models.
Saccharopine → Mitochondrial homeostasis source_derived_draftungraded
Experimental context and source evidence
affected_machinery
AASS
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine deficiency
experimental_model
Genetic and suppression experiments in worms and mice
limitations
Evidence is model-specific, not a toxicity threshold for normal human lysine intake.
organism
Caenorhabditis elegans and Mus musculus
plain_language
Accumulated saccharopine can harm mitochondria.
primary_references
[zhou2019] The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6363459/ DOI: 10.1083/jcb.201807204
tissue_or_cell_type
Worm hypodermis and mouse liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 242–252
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and suppression experiments in worms and mice · source_derived_draft · unverified_draft
### saccharopine-mitochondrial-toxicity Excess saccharopine disrupts mitochondrial morphology and function in AASS-domain mutant models. Plain language: Accumulated saccharopine can harm mitochondria. Condition category: machinery_impairment organism: Caenorhabditis elegans and Mus musculus tissue_or_cell_type: Worm hypodermis and mouse liver experimental_model: Genetic and suppression experiments in worms and mice limitations: Evidence is model-specific, not a toxicity threshold for normal human lysine intake. affected_machinery: AASS deficiency_not_equivalent: Dietary lysine deficiency [zhou2019] The lysine catabolite saccharopine impairs development by disrupting mitochondrial homeostasis (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6363459/ DOI: 10.1083/jcb.201807204
Complete structured claim and evidence
ALDH7A1 deficiency reduces aldehyde clearance, increasing AASA and its equilibrium partner P6C.
Antiquitin / ALDH7A1 → alpha-Aminoadipate semialdehyde source_derived_draftungraded
Experimental context and source evidence
affected_machinery
ALDH7A1
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine deficiency
experimental_model
Human patient biochemical and genetic evidence
limitations
Inherited enzyme failure is distinct from inadequate lysine intake.
organism
Homo sapiens
plain_language
An enzyme block allows reactive lysine metabolites to accumulate.
primary_references
[mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
tissue_or_cell_type
Affected tissues and body fluids
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 254–264
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human patient biochemical and genetic evidence · source_derived_draft · unverified_draft
### aldh7a1-metabolite-accumulation ALDH7A1 deficiency reduces aldehyde clearance, increasing AASA and its equilibrium partner P6C. Plain language: An enzyme block allows reactive lysine metabolites to accumulate. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Affected tissues and body fluids experimental_model: Human patient biochemical and genetic evidence limitations: Inherited enzyme failure is distinct from inadequate lysine intake. affected_machinery: ALDH7A1 deficiency_not_equivalent: Dietary lysine deficiency [mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
Complete structured claim and evidence
Accumulated P6C reacts with PLP through Knoevenagel condensation, reducing cofactor availability.
Delta1-piperideine-6-carboxylate → PLP source_derived_draftungraded
Experimental context and source evidence
affected_machinery
ALDH7A1 upstream clearance
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine or vitamin B6 deficiency
experimental_model
Chemical mechanism associated with human ALDH7A1 disease
limitations
Secondary cofactor loss does not demonstrate primary dietary vitamin B6 or lysine deficiency.
organism
Homo sapiens
plain_language
A lysine metabolite can trap active vitamin B6.
primary_references
[mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
tissue_or_cell_type
PDE-ALDH7A1 biochemical context
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical mechanism associated with human ALDH7A1 disease · source_derived_draft · unverified_draft
### p6c-plp-trapping Accumulated P6C reacts with PLP through Knoevenagel condensation, reducing cofactor availability. Plain language: A lysine metabolite can trap active vitamin B6. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: PDE-ALDH7A1 biochemical context experimental_model: Chemical mechanism associated with human ALDH7A1 disease limitations: Secondary cofactor loss does not demonstrate primary dietary vitamin B6 or lysine deficiency. affected_machinery: ALDH7A1 upstream clearance deficiency_not_equivalent: Dietary lysine or vitamin B6 deficiency [mills2006] Mutations in antiquitin in individuals with pyridoxine-dependent seizures. (2006). https://pubmed.ncbi.nlm.nih.gov/16491085/ DOI: 10.1038/nm1366
Complete structured claim and evidence
DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal.
DHTKD1 → 2-Oxoadipate source_derived_draftungraded
Experimental context and source evidence
affected_machinery
Oxoadipate-dehydrogenase E1
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine deficiency
experimental_model
Two human patients and isotope-traced fibroblasts
limitations
Biochemical causation is stronger than attribution of every neurological finding.
organism
Homo sapiens
plain_language
A downstream enzyme defect leaves oxoadipate uncleared.
primary_references
[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
Fibroblasts; clinical aciduria
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 278–288
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human patients and isotope-traced fibroblasts · source_derived_draft · unverified_draft
### dhtkd1-oxoadipate-accumulation DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal. Plain language: A downstream enzyme defect leaves oxoadipate uncleared. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Fibroblasts; clinical aciduria experimental_model: Two human patients and isotope-traced fibroblasts limitations: Biochemical causation is stronger than attribution of every neurological finding. affected_machinery: Oxoadipate-dehydrogenase E1 deficiency_not_equivalent: Dietary lysine deficiency [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
Complete structured claim and evidence
High lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury.
Glutaryl-CoA dehydrogenase / GCDH → Glutarate source_derived_draftungraded
Experimental context and source evidence
affected_machinery
GCDH
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Nutrient deficiency or normal human lysine intake
experimental_model
High-lysine dietary challenge of Gcdh-knockout mice
limitations
Genetic susceptibility and age are essential; does not show comparable toxicity in healthy humans.
organism
Mus musculus
plain_language
Lysine loading can worsen a blocked breakdown pathway.
primary_references
[zinnanti2006] A diet-induced mouse model for glutaric aciduria type I (2006). https://pubmed.ncbi.nlm.nih.gov/16446282/ DOI: 10.1093/brain/awl009
tissue_or_cell_type
Brain and systemic circulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-lysine dietary challenge of Gcdh-knockout mice · source_derived_draft · unverified_draft
### gcdh-high-lysine-glutarate High lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury. Plain language: Lysine loading can worsen a blocked breakdown pathway. Condition category: machinery_impairment organism: Mus musculus tissue_or_cell_type: Brain and systemic circulation experimental_model: High-lysine dietary challenge of Gcdh-knockout mice limitations: Genetic susceptibility and age are essential; does not show comparable toxicity in healthy humans. affected_machinery: GCDH deficiency_not_equivalent: Nutrient deficiency or normal human lysine intake [zinnanti2006] A diet-induced mouse model for glutaric aciduria type I (2006). https://pubmed.ncbi.nlm.nih.gov/16446282/ DOI: 10.1093/brain/awl009
Complete structured claim and evidence
P6C and acetoacetate form 2-OPP in chemical incubations including plasma.
Delta1-piperideine-6-carboxylate → 2S,6S-/2S,6R-6-(2-Oxopropyl)piperidine-2-carboxylate source_derived_draftungraded
Experimental context and source evidence
affected_machinery
ALDH7A1
availability_state
machinery_impairment Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine deficiency
experimental_model
Chemical incubations in aqueous solutions and human biological matrices
limitations
In-vivo formation is inferred; patient flux was not measured.
organism
Homo sapiens
plain_language
An accumulated intermediate can react with a ketone body.
primary_references
[engelke2021] Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy (2021). https://www.jci.org/articles/view/148272 DOI: 10.1172/JCI148272
tissue_or_cell_type
Body-fluid reaction model
trigger_kind
machinery_impairment Imported condition classification; unverified.
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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical incubations in aqueous solutions and human biological matrices · source_derived_draft · unverified_draft
### p6c-acetoacetate-2opp P6C and acetoacetate form 2-OPP in chemical incubations including plasma. Plain language: An accumulated intermediate can react with a ketone body. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Body-fluid reaction model experimental_model: Chemical incubations in aqueous solutions and human biological matrices limitations: In-vivo formation is inferred; patient flux was not measured. affected_machinery: ALDH7A1 deficiency_not_equivalent: Dietary lysine deficiency [engelke2021] Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy (2021). https://www.jci.org/articles/view/148272 DOI: 10.1172/JCI148272
Complete structured claim and evidence
Exposure to 10 mM 2-OPP increased zebrafish larval hyperactivity.
2S,6S-/2S,6R-6-(2-Oxopropyl)piperidine-2-carboxylate → Larval locomotor hyperactivity source_derived_draftungraded
Experimental context and source evidence
experimental_model
Wild-type Tüpfel long fin zebrafish F4 larvae exposed to 10 mM 2-OPP.
limitations
Classic convulsions were absent; this does not prove human seizure causation. This exposure arm did not have ALDH7A1 impairment; it is not a genetic-deficiency experiment.
organism
Danio rerio
plain_language
A disease-associated metabolite affected an animal behavior assay.
primary_references
[engelke2021] Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy (2021). https://www.jci.org/articles/view/148272 DOI: 10.1172/JCI148272
tissue_or_cell_type
Whole larvae
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 314–322
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type Tüpfel long fin zebrafish F4 larvae exposed to 10 mM 2-OPP. · source_derived_draft · unverified_draft
### 2opp-larval-hyperactivity Exposure to 10 mM 2-OPP increased zebrafish larval hyperactivity. Plain language: A disease-associated metabolite affected an animal behavior assay. Condition category: normal organism: Danio rerio tissue_or_cell_type: Whole larvae experimental_model: Wild-type Tüpfel long fin zebrafish F4 larvae exposed to 10 mM 2-OPP. limitations: Classic convulsions were absent; this does not prove human seizure causation. This exposure arm did not have ALDH7A1 impairment; it is not a genetic-deficiency experiment. [engelke2021] Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy (2021). https://www.jci.org/articles/view/148272 DOI: 10.1172/JCI148272
Complete structured claim and evidence
Elevated AASA was observed in an 18-patient PDE cohort with ALDH7A1 investigation, including during pyridoxine treatment.
alpha-Aminoadipate semialdehyde → Antiquitin / ALDH7A1 source_derived_draftungraded
Experimental context and source evidence
affected_machinery
ALDH7A1 under investigation
availability_state
biomarker_context Imported condition classification; unverified.
deficiency_not_equivalent
Dietary lysine deficiency
experimental_model
Human clinical cohort; plasma and urine assays
limitations
A biomarker is not itself a diagnosis or proof of dietary lysine deficiency.
organism
Homo sapiens
plain_language
AASA measurement can reveal disturbed lysine breakdown.
primary_references
[plecko2007] Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene (2007). https://pubmed.ncbi.nlm.nih.gov/17068770/ DOI: 10.1002/humu.20433
tissue_or_cell_type
Plasma and urine
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 324–334
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human clinical cohort; plasma and urine assays · source_derived_draft · unverified_draft
### aasa-pde-biomarker Elevated AASA was observed in an 18-patient PDE cohort with ALDH7A1 investigation, including during pyridoxine treatment. Plain language: AASA measurement can reveal disturbed lysine breakdown. Condition category: biomarker_context organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Human clinical cohort; plasma and urine assays limitations: A biomarker is not itself a diagnosis or proof of dietary lysine deficiency. affected_machinery: ALDH7A1 under investigation deficiency_not_equivalent: Dietary lysine deficiency [plecko2007] Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene (2007). https://pubmed.ncbi.nlm.nih.gov/17068770/ DOI: 10.1002/humu.20433
Complete structured claim and evidence
CRYM ketimine reductase reduces P2C to L-pipecolate using reduced nicotinamide cofactors.
Delta1-piperideine-2-carboxylate → L-Pipecolate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human CRYM and mammalian enzyme substrate assays
limitations
Catalytic capacity does not determine the route's quantitative contribution to human brain lysine clearance.
organism
Homo sapiens enzyme; ovine enzyme used for initial purification
plain_language
A ring-shaped intermediate can be reduced to pipecolate.
primary_references
[hallen2011] Mammalian forebrain ketimine reductase identified as mu-crystallin; potential regulation by thyroid hormones. (2011). https://pubmed.ncbi.nlm.nih.gov/21332720/ DOI: 10.1111/j.1471-4159.2011.07220.x [hallen2015] Insights into Enzyme Catalysis and Thyroid Hormone Regulation of Cerebral Ketimine Reductase/mu-Crystallin Under Physiological Conditions. (2015). https://pubmed.ncbi.nlm.nih.gov/25931162/ DOI: 10.1007/s11064-015-1590-5
tissue_or_cell_type
Cytosolic enzyme; forebrain biochemical context
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 336–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human CRYM and mammalian enzyme substrate assays · source_derived_draft · unverified_draft
### crym-p2c-reduction CRYM ketimine reductase reduces P2C to L-pipecolate using reduced nicotinamide cofactors. Plain language: A ring-shaped intermediate can be reduced to pipecolate. Condition category: normal organism: Homo sapiens enzyme; ovine enzyme used for initial purification tissue_or_cell_type: Cytosolic enzyme; forebrain biochemical context experimental_model: Recombinant human CRYM and mammalian enzyme substrate assays limitations: Catalytic capacity does not determine the route's quantitative contribution to human brain lysine clearance. [hallen2011] Mammalian forebrain ketimine reductase identified as mu-crystallin; potential regulation by thyroid hormones. (2011). https://pubmed.ncbi.nlm.nih.gov/21332720/ DOI: 10.1111/j.1471-4159.2011.07220.x [hallen2015] Insights into Enzyme Catalysis and Thyroid Hormone Regulation of Cerebral Ketimine Reductase/mu-Crystallin Under Physiological Conditions. (2015). https://pubmed.ncbi.nlm.nih.gov/25931162/ DOI: 10.1007/s11064-015-1590-5
Complete structured claim and evidence
At the cytosolic 80S ribosome, the alpha-amino group of A-site lysyl-tRNA accepts the P-site nascent peptide, incorporating lysine into a peptide bond; the extended chain remains attached to the incoming tRNA.
Lysyl-tRNA-Lys → Protein-bound lysine residue source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human cell lysate translation products; rabbit reticulocyte ribosome-nascent-chain cryo-EM
limitations
AAG-coded translation controls directly show elongation. The structural experiment concerns poly(A)-dependent stalling; it does not establish a dietary deficiency response or instant release of the lysine-carrying tRNA.
organism
Homo sapiens and Oryctolagus cuniculus
plain_language
The ribosome adds charged lysine to a growing protein chain.
primary_references
[chandrasekaran2019] Mechanism of ribosome stalling during translation of a poly(A) tail (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6900289/ DOI: 10.1038/s41594-019-0331-x
tissue_or_cell_type
Cytosolic translation; cultured-cell lysate and reticulocyte lysate
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 347–355
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell lysate translation products; rabbit reticulocyte ribosome-nascent-chain cryo-EM · source_derived_draft · unverified_draft
### ribosomal-lysine-incorporation At the cytosolic 80S ribosome, the alpha-amino group of A-site lysyl-tRNA accepts the P-site nascent peptide, incorporating lysine into a peptide bond; the extended chain remains attached to the incoming tRNA. Plain language: The ribosome adds charged lysine to a growing protein chain. Condition category: normal organism: Homo sapiens and Oryctolagus cuniculus tissue_or_cell_type: Cytosolic translation; cultured-cell lysate and reticulocyte lysate experimental_model: Human cell lysate translation products; rabbit reticulocyte ribosome-nascent-chain cryo-EM limitations: AAG-coded translation controls directly show elongation. The structural experiment concerns poly(A)-dependent stalling; it does not establish a dietary deficiency response or instant release of the lysine-carrying tRNA. [chandrasekaran2019] Mechanism of ribosome stalling during translation of a poly(A) tail (2019). https://pmc.ncbi.nlm.nih.gov/articles/PMC6900289/ DOI: 10.1038/s41594-019-0331-x
Complete structured claim and evidence
Short-chain enoyl-CoA hydratase ECHS1 hydrates trans-crotonyl-CoA to (S)-3-hydroxybutyryl-CoA.
Crotonyl-CoA → (S)-3-Hydroxybutyryl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Crotonyl-CoA hydratase assays in control human fibroblasts
limitations
This shared short-chain reaction can process lysine-derived crotonyl-CoA, but the assay does not trace its carbon from lysine. Disease results are not used to label the control reaction as machinery impairment.
organism
Homo sapiens
plain_language
Water is added across the four-carbon intermediate's double bond.
primary_references
[ferdinandusse2015] Clinical and biochemical characterization of four patients with mutations in ECHS1 (2015). https://link.springer.com/article/10.1186/s13023-015-0290-1 DOI: 10.1186/s13023-015-0290-1
tissue_or_cell_type
Fibroblasts; mitochondrial enzyme
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 357–365
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crotonyl-CoA hydratase assays in control human fibroblasts · source_derived_draft · unverified_draft
### echs1-crotonyl-coa-hydration Short-chain enoyl-CoA hydratase ECHS1 hydrates trans-crotonyl-CoA to (S)-3-hydroxybutyryl-CoA. Plain language: Water is added across the four-carbon intermediate's double bond. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Fibroblasts; mitochondrial enzyme experimental_model: Crotonyl-CoA hydratase assays in control human fibroblasts limitations: This shared short-chain reaction can process lysine-derived crotonyl-CoA, but the assay does not trace its carbon from lysine. Disease results are not used to label the control reaction as machinery impairment. [ferdinandusse2015] Clinical and biochemical characterization of four patients with mutations in ECHS1 (2015). https://link.springer.com/article/10.1186/s13023-015-0290-1 DOI: 10.1186/s13023-015-0290-1
Complete structured claim and evidence
The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH.
(S)-3-Hydroxybutyryl-CoA → Acetoacetyl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified recombinant human HADH; substrate/product-cofactor crystal complexes
limitations
HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people.
organism
Homo sapiens
plain_language
The four-carbon hydroxy intermediate is oxidized to a keto intermediate.
primary_references
[barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200
tissue_or_cell_type
Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 367–375
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human HADH; substrate/product-cofactor crystal complexes · source_derived_draft · unverified_draft
### hadh-hydroxybutyryl-coa-oxidation The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH. Plain language: The four-carbon hydroxy intermediate is oxidized to a keto intermediate. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study experimental_model: Purified recombinant human HADH; substrate/product-cofactor crystal complexes limitations: HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people. [barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200
Complete structured claim and evidence
Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules.
Acetoacetyl-CoA → Acetyl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures
limitations
Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1.
organism
Homo sapiens
plain_language
The four-carbon intermediate is split into two acetyl-CoA molecules.
primary_references
[haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192
tissue_or_cell_type
Mitochondrial matrix enzyme; recombinant protein study
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 377–385
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures · source_derived_draft · unverified_draft
### acat1-acetoacetyl-coa-thiolysis Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules. Plain language: The four-carbon intermediate is split into two acetyl-CoA molecules. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix enzyme; recombinant protein study experimental_model: Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures limitations: Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1. [haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192
Complete structured claim and evidence
PLOD1 hydroxylates selected collagen-bound lysine residues to hydroxylysine.
PLOD1 → Collagen-bound lysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human lysyl hydroxylase characterization.
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 enzyme adds a hydroxyl group to selected lysines in collagen.
primary_references
[plod1-1992] Cloning of human lysyl hydroxylase: complete cDNA-derived amino acid sequence and assignment of the gene (PLOD) to chromosome 1p36.3--p36.2 (1992). https://pubmed.ncbi.nlm.nih.gov/1577494/ DOI: 10.1016/0888-7543(92)90202-4
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 387–395
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human lysyl hydroxylase characterization. · source_derived_draft · unverified_draft
### plod1-collagen-hydroxylation PLOD1 hydroxylates selected collagen-bound lysine residues to hydroxylysine. Plain language: An enzyme adds a hydroxyl group to selected lysines in collagen. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human lysyl hydroxylase characterization. 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. [plod1-1992] Cloning of human lysyl hydroxylase: complete cDNA-derived amino acid sequence and assignment of the gene (PLOD) to chromosome 1p36.3--p36.2 (1992). https://pubmed.ncbi.nlm.nih.gov/1577494/ DOI: 10.1016/0888-7543(92)90202-4
Complete structured claim and evidence
PLOD2/LH2 hydroxylates collagen telopeptide lysines, influencing the subsequent cross-link pathway.
PLOD2 → Collagen telopeptide lysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human patient bone collagen biochemistry and PLOD2 variant analysis.
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
This enzyme prepares lysines near collagen ends for particular cross-links.
primary_references
[plod2-bruck-2021] Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC7990156/
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 397–405
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human patient bone collagen biochemistry and PLOD2 variant analysis. · source_derived_draft · unverified_draft
### plod2-telopeptide-hydroxylation PLOD2/LH2 hydroxylates collagen telopeptide lysines, influencing the subsequent cross-link pathway. Plain language: This enzyme prepares lysines near collagen ends for particular cross-links. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human patient bone collagen biochemistry and PLOD2 variant analysis. 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. [plod2-bruck-2021] Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC7990156/
Complete structured claim and evidence
FKBP65 supports LH2/PLOD2 dimer formation in the tested collagen-producing cell systems.
FKBP10 → PLOD2 dimer source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human collagen-producing fibroblasts and expression constructs; predominantly LH2B dimerization/interaction assays.
limitations
This is an experimentally scoped assembly mechanism; free lysine supplementation was not tested.
organism
Human
plain_language
A helper protein helps assemble the collagen-modifying enzyme.
primary_references
[plod2-fkbp65-2016] Disentangling mechanisms involved in collagen pyridinoline cross-linking: The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2 (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4932945/ DOI: 10.1073/pnas.1600074113
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 407–415
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human collagen-producing fibroblasts and expression constructs; predominantly LH2B dimerization/interaction assays. · source_derived_draft · unverified_draft
### fkbp65-plod2-dimer FKBP65 supports LH2/PLOD2 dimer formation in the tested collagen-producing cell systems. Plain language: A helper protein helps assemble the collagen-modifying enzyme. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human collagen-producing fibroblasts and expression constructs; predominantly LH2B dimerization/interaction assays. limitations: This is an experimentally scoped assembly mechanism; free lysine supplementation was not tested. [plod2-fkbp65-2016] Disentangling mechanisms involved in collagen pyridinoline cross-linking: The immunophilin FKBP65 is critical for dimerization of lysyl hydroxylase 2 (2016). https://pmc.ncbi.nlm.nih.gov/articles/PMC4932945/ DOI: 10.1073/pnas.1600074113
Complete structured claim and evidence
PLOD3 hydroxylates peptidyl lysine using Fe(II), 2-oxoglutarate and oxygen.
PLOD3 → Collagen-bound lysine residues source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Ascorbate supports sustained lysyl-hydroxylase activity; the enzyme can initially turn over without ascorbate.
L-Ascorbate → Collagen lysyl hydroxylase family source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified chick-embryo enzyme kinetics.
limitations
Family-level enzyme preparation, not a human PLOD isoform comparison or lysine-supplement trial.
organism
Chicken
plain_language
Vitamin C supports the reaction, but is not consumed in every coupled turnover.
primary_references
[plod-cofactor-1980] Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. (1980). https://pubmed.ncbi.nlm.nih.gov/6766066/ DOI: 10.1016/0005-2744(80)90040-6
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 427–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified chick-embryo enzyme kinetics. · source_derived_draft · unverified_draft
### ascorbate-lysyl-hydroxylase Ascorbate supports sustained lysyl-hydroxylase activity; the enzyme can initially turn over without ascorbate. Plain language: Vitamin C supports the reaction, but is not consumed in every coupled turnover. Condition category: normal organism: Chicken tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified chick-embryo enzyme kinetics. limitations: Family-level enzyme preparation, not a human PLOD isoform comparison or lysine-supplement trial. [plod-cofactor-1980] Studies on the lysyl hydroxylase reaction. I. Initial velocity kinetics and related aspects. (1980). https://pubmed.ncbi.nlm.nih.gov/6766066/ DOI: 10.1016/0005-2744(80)90040-6
Complete structured claim and evidence
COLGALT1 transfers galactose from UDP-galactose to collagen hydroxylysine.
COLGALT1 → Collagen-bound 5-hydroxylysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human COLGALT1 with collagen peptides.
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
A sugar is attached to a lysine residue that has already been hydroxylated.
primary_references
[colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 437–445
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human COLGALT1 with collagen peptides. · source_derived_draft · unverified_draft
### colgalt1-galactosylation COLGALT1 transfers galactose from UDP-galactose to collagen hydroxylysine. Plain language: A sugar is attached to a lysine residue that has already been hydroxylated. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Recombinant human COLGALT1 with collagen peptides. 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. [colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
Complete structured claim and evidence
Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay.
Mn2+ → COLGALT1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human COLGALT1 metal-substitution assays.
limitations
Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive.
organism
Human
plain_language
Manganese is a catalytic partner for this collagen-sugar enzyme.
primary_references
[colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 447–455
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human COLGALT1 metal-substitution assays. · source_derived_draft · unverified_draft
### manganese-colgalt1 Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay. Plain language: Manganese is a catalytic partner for this collagen-sugar enzyme. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified human COLGALT1 metal-substitution assays. limitations: Metal dependence does not establish which nutrient is limiting in a person; magnesium is not claimed universally inactive. [colgalt1-2025] Molecular structure and enzymatic mechanism of the human collagen hydroxylysine galactosyltransferase GLT25D1/COLGALT1 (2025). https://www.nature.com/articles/s41467-025-59017-5 DOI: 10.1038/s41467-025-59017-5
Complete structured claim and evidence
PLOD3 transfers glucose from UDP-glucose onto galactosyl-hydroxylysine in collagen.
PLOD3 → Collagen galactosyl-hydroxylysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human PLOD3-COLGALT1 complex structure 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
A second sugar can be added after galactose.
primary_references
[kog-glycosylation-2025] The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation (2025). https://www.nature.com/articles/s41467-025-57768-9 DOI: 10.1038/s41467-025-57768-9
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 457–465
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PLOD3-COLGALT1 complex structure and biochemical assays. · source_derived_draft · unverified_draft
### plod3-glucosylation PLOD3 transfers glucose from UDP-glucose onto galactosyl-hydroxylysine in collagen. Plain language: A second sugar can be added after galactose. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human PLOD3-COLGALT1 complex structure 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. [kog-glycosylation-2025] The structural basis for the human procollagen lysine hydroxylation and dual-glycosylation (2025). https://www.nature.com/articles/s41467-025-57768-9 DOI: 10.1038/s41467-025-57768-9
Complete structured claim and evidence
Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide.
Lysyl oxidase enzyme family → Collagen/elastin peptidyl lysine substrates source_derived_draftungraded
Experimental context and source evidence
experimental_model
LOXL2 assay development and total-family activity detection in cultured cells and tissue.
limitations
Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury.
organism
Mammalian cells/tissues and recombinant LOXL2; see study methods
plain_language
An enzyme creates reactive attachment sites used in matrix cross-linking.
primary_references
[lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 467–475
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOXL2 assay development and total-family activity detection in cultured cells and tissue. · source_derived_draft · unverified_draft
### lox-peptidyl-lysine-oxidation Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide. Plain language: An enzyme creates reactive attachment sites used in matrix cross-linking. Condition category: normal organism: Mammalian cells/tissues and recombinant LOXL2; see study methods tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: LOXL2 assay development and total-family activity detection in cultured cells and tissue. limitations: Substrate sites and enzyme-family members differ; peroxide production alone does not establish systemic oxidative injury. [lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/
Complete structured claim and evidence
Lysyl-oxidase activity can convert collagen hydroxylysine side chains to hydroxyallysine.
Lysyl oxidase enzyme family → Collagen-bound 5-hydroxylysine residues source_derived_draftungraded
Experimental context and source evidence
experimental_model
LOXL2 assay development with extracellular matrix; family-level reaction context.
limitations
This is a reaction-class record; not every hydroxylysine site is an accessible LOX substrate.
organism
Mammalian cells/tissues and recombinant LOXL2; see study methods
plain_language
Hydroxylated lysines provide a different aldehyde starting point for cross-links.
primary_references
[lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 477–485
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LOXL2 assay development with extracellular matrix; family-level reaction context. · source_derived_draft · unverified_draft
### lox-hydroxylysine-oxidation Lysyl-oxidase activity can convert collagen hydroxylysine side chains to hydroxyallysine. Plain language: Hydroxylated lysines provide a different aldehyde starting point for cross-links. Condition category: normal organism: Mammalian cells/tissues and recombinant LOXL2; see study methods tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: LOXL2 assay development with extracellular matrix; family-level reaction context. limitations: This is a reaction-class record; not every hydroxylysine site is an accessible LOX substrate. [lox-assay-2021] An in situ activity assay for lysyl oxidases (2021). https://pubmed.ncbi.nlm.nih.gov/34226627/
Complete structured claim and evidence
A protein-derived lysine-tyrosylquinone cofactor was identified in bovine aortic lysyl oxidase.
Protein-bound lysine tyrosylquinone → LOX source_derived_draftungraded
Experimental context and source evidence
experimental_model
Bovine aortic enzyme sequencing, mass spectrometry and spectroscopy.
limitations
This protein-bound cofactor is neither a vitamin nor free lysine, and the experiment did not test dietary supplementation.
organism
Cattle
plain_language
Two amino-acid side chains in the enzyme form part of its catalytic machinery.
primary_references
[lox-ltq-1996] A crosslinked cofactor in lysyl oxidase: redox function for amino acid side chains (1996). https://pubmed.ncbi.nlm.nih.gov/8688089/ DOI: 10.1126/science.273.5278.1078
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 487–495
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bovine aortic enzyme sequencing, mass spectrometry and spectroscopy. · source_derived_draft · unverified_draft
### lox-ltq-cofactor A protein-derived lysine-tyrosylquinone cofactor was identified in bovine aortic lysyl oxidase. Plain language: Two amino-acid side chains in the enzyme form part of its catalytic machinery. Condition category: normal organism: Cattle tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Bovine aortic enzyme sequencing, mass spectrometry and spectroscopy. limitations: This protein-bound cofactor is neither a vitamin nor free lysine, and the experiment did not test dietary supplementation. [lox-ltq-1996] A crosslinked cofactor in lysyl oxidase: redox function for amino acid side chains (1996). https://pubmed.ncbi.nlm.nih.gov/8688089/ DOI: 10.1126/science.273.5278.1078
Complete structured claim and evidence
Dietary copper availability altered tendon lysyl-oxidase activation in the chick experiments.
Copper(II) ion → Lysyl oxidase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Chicks receiving diets differing in copper; tendon enzyme assays.
limitations
Copper manipulation in chicks, not evidence of dietary lysine deficiency or a human copper/lysine dose recommendation.
organism
Chicken
plain_language
Insufficient copper can limit a lysine-processing enzyme even when its substrate is present.
primary_references
[lox-copper-1999] Activation of chick tendon lysyl oxidase in response to dietary copper (1999). https://pubmed.ncbi.nlm.nih.gov/10573541/
tissue_or_cell_type
Tendon
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 497–505
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chicks receiving diets differing in copper; tendon enzyme assays. · source_derived_draft · unverified_draft
### copper-insufficiency-lox Dietary copper availability altered tendon lysyl-oxidase activation in the chick experiments. Plain language: Insufficient copper can limit a lysine-processing enzyme even when its substrate is present. Condition category: nutrient_deficiency organism: Chicken tissue_or_cell_type: Tendon experimental_model: Chicks receiving diets differing in copper; tendon enzyme assays. limitations: Copper manipulation in chicks, not evidence of dietary lysine deficiency or a human copper/lysine dose recommendation. [lox-copper-1999] Activation of chick tendon lysyl oxidase in response to dietary copper (1999). https://pubmed.ncbi.nlm.nih.gov/10573541/
Complete structured claim and evidence
Pathogenic PLOD2 variants were associated with telopeptide underhydroxylation and abnormal bone collagen cross-links.
PLOD2 → Collagen cross-link pattern source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Bone collagen from a patient with compound-heterozygous PLOD2 variants.
limitations
Rare genetic disease; cannot be generalized to low lysine intake or used as evidence that lysine treats Bruck syndrome.
organism
Human
plain_language
An impaired enzyme can change collagen cross-links without a shortage of dietary lysine.
primary_references
[plod2-bruck-2021] Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC7990156/
tissue_or_cell_type
Bone
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 507–515
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bone collagen from a patient with compound-heterozygous PLOD2 variants. · source_derived_draft · unverified_draft
### plod2-impairment-crosslinks Pathogenic PLOD2 variants were associated with telopeptide underhydroxylation and abnormal bone collagen cross-links. Plain language: An impaired enzyme can change collagen cross-links without a shortage of dietary lysine. Condition category: machinery_impairment organism: Human tissue_or_cell_type: Bone experimental_model: Bone collagen from a patient with compound-heterozygous PLOD2 variants. limitations: Rare genetic disease; cannot be generalized to low lysine intake or used as evidence that lysine treats Bruck syndrome. [plod2-bruck-2021] Abnormal Bone Collagen Cross-Linking in Osteogenesis Imperfecta/Bruck Syndrome Caused by Compound Heterozygous PLOD2 Mutations (2021). https://pmc.ncbi.nlm.nih.gov/articles/PMC7990156/
Complete structured claim and evidence
Expressed LOX Ser280Arg and Ser348Arg variants had lower catalytic activity than wild-type LOX.
LOX → Lysyl oxidase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human-family genetic study with expressed mutant-enzyme assays.
limitations
Variant-specific activity measurements; free lysine was not shown to rescue the defect.
organism
Human
plain_language
Some inherited enzyme changes reduce activity despite the presence of lysine substrates.
primary_references
[lox-variants-2016] LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections (2016). https://pubmed.ncbi.nlm.nih.gov/26838787/ DOI: 10.1161/CIRCRESAHA.115.307130
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 517–525
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human-family genetic study with expressed mutant-enzyme assays. · source_derived_draft · unverified_draft
### lox-variants-enzyme-activity Expressed LOX Ser280Arg and Ser348Arg variants had lower catalytic activity than wild-type LOX. Plain language: Some inherited enzyme changes reduce activity despite the presence of lysine substrates. Condition category: machinery_impairment organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human-family genetic study with expressed mutant-enzyme assays. limitations: Variant-specific activity measurements; free lysine was not shown to rescue the defect. [lox-variants-2016] LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections (2016). https://pubmed.ncbi.nlm.nih.gov/26838787/ DOI: 10.1161/CIRCRESAHA.115.307130
Complete structured claim and evidence
EP300 transfers an acetyl group from acetyl-CoA to a protein lysine side chain.
EP300 → Protein-bound lysine residue source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human p300 catalytic-domain structure 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
Acetyl groups can be written onto lysines already present in proteins.
primary_references
[p300-2008] The structural basis of protein acetylation by the p300/CBP transcriptional coactivator (2008). https://pubmed.ncbi.nlm.nih.gov/18273021/ DOI: 10.1038/nature06546
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 527–535
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human p300 catalytic-domain structure and biochemical assays. · source_derived_draft · unverified_draft
### ep300-lysine-acetylation EP300 transfers an acetyl group from acetyl-CoA to a protein lysine side chain. Plain language: Acetyl groups can be written onto lysines already present in proteins. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human p300 catalytic-domain structure 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. [p300-2008] The structural basis of protein acetylation by the p300/CBP transcriptional coactivator (2008). https://pubmed.ncbi.nlm.nih.gov/18273021/ DOI: 10.1038/nature06546
Complete structured claim and evidence
Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction.
SIRT1 → Histone H4 acetylated at K16 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human enzyme assays and cultured-cell SIRT1 perturbation.
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
A different enzyme removes a lysine modification using NAD+.
primary_references
[sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 537–545
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme assays and cultured-cell SIRT1 perturbation. · source_derived_draft · unverified_draft
### sirt1-h4k16-deacetylation Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction. Plain language: A different enzyme removes a lysine modification using NAD+. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human enzyme assays and cultured-cell SIRT1 perturbation. 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. [sirt1-2004] Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin (2004). https://pubmed.ncbi.nlm.nih.gov/15469825/ DOI: 10.1016/j.molcel.2004.08.031
Complete structured claim and evidence
SETD7 transfers a methyl group from SAM to histone H3 Lys4 in peptide assays.
SETD7 → Histone H3 unmethylated at K4 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human SET7/9 structure and H3-peptide assays.
limitations
Peptide activity does not establish SETD7 as the dominant H3K4 writer in every chromatin context. 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
SAM provides the methyl group; the protein-bound lysine receives it.
primary_references
[setd7-2002] Crystal structure and functional analysis of the histone methyltransferase SET7/9 (2002). https://pubmed.ncbi.nlm.nih.gov/12372304/ DOI: 10.1016/s0092-8674(02)00964-9
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 547–555
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SET7/9 structure and H3-peptide assays. · source_derived_draft · unverified_draft
### setd7-h3k4-methylation SETD7 transfers a methyl group from SAM to histone H3 Lys4 in peptide assays. Plain language: SAM provides the methyl group; the protein-bound lysine receives it. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified human SET7/9 structure and H3-peptide assays. limitations: Peptide activity does not establish SETD7 as the dominant H3K4 writer in every chromatin context. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [setd7-2002] Crystal structure and functional analysis of the histone methyltransferase SET7/9 (2002). https://pubmed.ncbi.nlm.nih.gov/12372304/ DOI: 10.1016/s0092-8674(02)00964-9
Complete structured claim and evidence
KDM1A/LSD1 oxidatively removes a methyl group from H3K4me2 through a flavin-dependent reaction.
KDM1A → Histone H3 dimethylated at K4 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified LSD1 enzyme / histone assays and cellular RNA interference.
limitations
Do not extend this specific activity to trimethyllysine or every histone site. 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
Some lysine methyl marks can be erased by a flavin enzyme.
primary_references
[lsd1-2004] Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 (2004). https://pubmed.ncbi.nlm.nih.gov/15620353/ DOI: 10.1016/j.cell.2004.12.012
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 557–565
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified LSD1 enzyme / histone assays and cellular RNA interference. · source_derived_draft · unverified_draft
### kdm1a-h3k4-demethylation KDM1A/LSD1 oxidatively removes a methyl group from H3K4me2 through a flavin-dependent reaction. Plain language: Some lysine methyl marks can be erased by a flavin enzyme. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Purified LSD1 enzyme / histone assays and cellular RNA interference. limitations: Do not extend this specific activity to trimethyllysine or every histone site. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [lsd1-2004] Histone demethylation mediated by the nuclear amine oxidase homolog LSD1 (2004). https://pubmed.ncbi.nlm.nih.gov/15620353/ DOI: 10.1016/j.cell.2004.12.012
Complete structured claim and evidence
KDM4A/JMJD2A can convert H3K9me3 to H3K9me2 using Fe(II), oxygen and 2-oxoglutarate.
KDM4A → Histone H3 trimethylated at K9 source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
DHPS transfers spermidine-derived aminobutyl onto eIF5A Lys50 to form deoxyhypusine.
DHPS → eIF5A1 with unmodified Lys50 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human DHPS structural biochemistry.
limitations
NAD cycles during catalysis; it is not represented as a net consumed substrate here. 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
A particular protein lysine becomes a specialized translation-factor residue.
primary_references
[dhps-2020] Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase (2020). https://pubmed.ncbi.nlm.nih.gov/32235505/
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 578–586
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DHPS structural biochemistry. · source_derived_draft · unverified_draft
### dhps-eif5a-deoxyhypusine DHPS transfers spermidine-derived aminobutyl onto eIF5A Lys50 to form deoxyhypusine. Plain language: A particular protein lysine becomes a specialized translation-factor residue. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human DHPS structural biochemistry. limitations: NAD cycles during catalysis; it is not represented as a net consumed substrate here. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [dhps-2020] Half Way to Hypusine-Structural Basis for Substrate Recognition by Human Deoxyhypusine Synthase (2020). https://pubmed.ncbi.nlm.nih.gov/32235505/
Complete structured claim and evidence
DOHH hydroxylates deoxyhypusine-eIF5A to hypusine-eIF5A using its oxygen-activating diiron center.
DOHH → eIF5A1 with deoxyhypusine at residue 50 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human DOHH structures and spectroscopy.
limitations
DOHH is a diiron enzyme, not a 2-oxoglutarate-dependent hydroxylase. 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
A second enzyme completes the special modification.
primary_references
[dohh-2015] Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination (2015). https://pubmed.ncbi.nlm.nih.gov/25865244/ DOI: 10.1016/j.str.2015.03.002
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 588–596
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DOHH structures and spectroscopy. · source_derived_draft · unverified_draft
### dohh-eif5a-hypusine DOHH hydroxylates deoxyhypusine-eIF5A to hypusine-eIF5A using its oxygen-activating diiron center. Plain language: A second enzyme completes the special modification. Condition category: normal organism: Human tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Human DOHH structures and spectroscopy. limitations: DOHH is a diiron enzyme, not a 2-oxoglutarate-dependent hydroxylase. This reaction modifies lysine already in a protein. It does not show that extra oral lysine increases the reaction or improves a clinical outcome. [dohh-2015] Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination (2015). https://pubmed.ncbi.nlm.nih.gov/25865244/ DOI: 10.1016/j.str.2015.03.002
Complete structured claim and evidence
Ubiquitin Gly76 can form an isopeptide bond to Lys48 of an adjacent ubiquitin in a chain.
Ubiquitin → Lys48-linked polyubiquitin chains source_derived_draftungraded
Experimental context and source evidence
experimental_model
Multiubiquitination of an experimentally targeted beta-galactosidase substrate.
limitations
This describes one chain topology; ubiquitin has other linkages and not all ubiquitination means degradation.
organism
Experimental ubiquitin-conjugation system
plain_language
Protein-bound lysine can be an attachment site for a protein tag.
primary_references
[ubiquitin-k48-1989] A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein (1989). https://pubmed.ncbi.nlm.nih.gov/2538923/
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 598–606
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multiubiquitination of an experimentally targeted beta-galactosidase substrate. · source_derived_draft · unverified_draft
### ubiquitin-k48-chain Ubiquitin Gly76 can form an isopeptide bond to Lys48 of an adjacent ubiquitin in a chain. Plain language: Protein-bound lysine can be an attachment site for a protein tag. Condition category: normal organism: Experimental ubiquitin-conjugation system tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Multiubiquitination of an experimentally targeted beta-galactosidase substrate. limitations: This describes one chain topology; ubiquitin has other linkages and not all ubiquitination means degradation. [ubiquitin-k48-1989] A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein (1989). https://pubmed.ncbi.nlm.nih.gov/2538923/
Complete structured claim and evidence
The 26S proteasome degrades suitable Lys48-polyubiquitinated substrates; chain trimming permits continued substrate loading.
Lys48-polyubiquitinated protein substrates → 26S proteasome source_derived_draftungraded
Experimental context and source evidence
experimental_model
Biochemical proteasome/polyubiquitin assays.
limitations
Recognition and substrate accessibility matter; this is not a prediction that dietary lysine accelerates protein destruction.
organism
Experimental proteasome system
plain_language
A lysine-linked tag can help deliver a protein for breakdown.
primary_references
[proteasome-trimming-2011] Ubiquitin chain trimming recycles the substrate binding sites of the 26 S proteasome and promotes degradation of lysine 48-linked polyubiquitin conjugates (2011). https://pubmed.ncbi.nlm.nih.gov/21632534/
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 608–616
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical proteasome/polyubiquitin assays. · source_derived_draft · unverified_draft
### k48-proteasome-degradation The 26S proteasome degrades suitable Lys48-polyubiquitinated substrates; chain trimming permits continued substrate loading. Plain language: A lysine-linked tag can help deliver a protein for breakdown. Condition category: normal organism: Experimental proteasome system tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: Biochemical proteasome/polyubiquitin assays. limitations: Recognition and substrate accessibility matter; this is not a prediction that dietary lysine accelerates protein destruction. [proteasome-trimming-2011] Ubiquitin chain trimming recycles the substrate binding sites of the 26 S proteasome and promotes degradation of lysine 48-linked polyubiquitin conjugates (2011). https://pubmed.ncbi.nlm.nih.gov/21632534/
Complete structured claim and evidence
E. coli CadA converts lysine to cadaverine and CO2 while consuming a proton during acid stress.
E. coli CadA → L-Lysine source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
E. coli CadB couples lysine uptake to cadaverine export in the Cad acid-response system.
E. coli CadB → Lysine/cadaverine membrane exchange source_derived_draftungraded
Experimental context and source evidence
experimental_model
E. coli cells and membrane vesicles expressing CadB; cadaverine uptake/excretion and lysine exchange assays.
limitations
Bacterial antiport, not the mammalian intestinal lysine transporter or a clinical dysbiosis claim.
organism
Escherichia coli
plain_language
Transport connects extracellular lysine with bacterial cadaverine release.
primary_references
[cadb-2004] Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli (2004). https://pubmed.ncbi.nlm.nih.gov/14982633/ DOI: 10.1046/j.1365-2958.2003.03913.x
tissue_or_cell_type
Not specified as a whole tissue; see experimental model.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 628–636
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · E. coli cells and membrane vesicles expressing CadB; cadaverine uptake/excretion and lysine exchange assays. · source_derived_draft · unverified_draft
### bacterial-cadb-exchange E. coli CadB couples lysine uptake to cadaverine export in the Cad acid-response system. Plain language: Transport connects extracellular lysine with bacterial cadaverine release. Condition category: normal organism: Escherichia coli tissue_or_cell_type: Not specified as a whole tissue; see experimental model. experimental_model: E. coli cells and membrane vesicles expressing CadB; cadaverine uptake/excretion and lysine exchange assays. limitations: Bacterial antiport, not the mammalian intestinal lysine transporter or a clinical dysbiosis claim. [cadb-2004] Excretion and uptake of cadaverine by CadB and its physiological functions in Escherichia coli (2004). https://pubmed.ncbi.nlm.nih.gov/14982633/ DOI: 10.1046/j.1365-2958.2003.03913.x
Complete structured claim and evidence
In seven men receiving graded lysine intakes, indicator phenylalanine oxidation fell until a breakpoint and then remained approximately constant.
L-Lysine → Phenylalanine oxidation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Controlled isotope feeding experiment
limitations
Small male sample; surrogate measure; plateau is not evidence that extra lysine beyond adequacy builds more muscle.
organism
Homo sapiens
plain_language
When lysine was limiting, less of another amino acid was retained; providing more lysine changed that metabolic readout up to a plateau.
primary_references
[zello1993] Dietary lysine requirement of young adult males determined by oxidation of L-[1-13C]phenylalanine (1993). https://pubmed.ncbi.nlm.nih.gov/8476044/ DOI: 10.1152/ajpendo.1993.264.4.E677
tissue_or_cell_type
Whole-body amino-acid metabolism
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 638–646
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled isotope feeding experiment · source_derived_draft · unverified_draft
### lysine-intake-indicator-oxidation In seven men receiving graded lysine intakes, indicator phenylalanine oxidation fell until a breakpoint and then remained approximately constant. Plain language: When lysine was limiting, less of another amino acid was retained; providing more lysine changed that metabolic readout up to a plateau. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Whole-body amino-acid metabolism experimental_model: Controlled isotope feeding experiment limitations: Small male sample; surrogate measure; plateau is not evidence that extra lysine beyond adequacy builds more muscle. [zello1993] Dietary lysine requirement of young adult males determined by oxidation of L-[1-13C]phenylalanine (1993). https://pubmed.ncbi.nlm.nih.gov/8476044/ DOI: 10.1152/ajpendo.1993.264.4.E677
Complete structured claim and evidence
The tested whole-wheat bread supplied lysine with an estimated 90% metabolic availability, while low lysine concentration still limited its protein quality.
L-Lysine → Lysine metabolic availability source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized intake-order repeated-measures experiment in five young men
exposure
Lysine supplied by the tested whole-wheat bread; bread is a food matrix recorded in context, not a chemical-species entity.
limitations
Specific bread and small sample; metabolic availability is method-dependent and does not establish adequacy of all wheat-based diets.
organism
Homo sapiens
plain_language
A food can deliver most of its lysine efficiently yet contain too little lysine relative to other amino acids.
primary_references
[tulnoor2025] Lysine from Whole Wheat Bread Consumed by Healthy Adult Males Has High Metabolic Availability When Assessed Using the Indicator Amino Acid Oxidation Method (2025). https://pubmed.ncbi.nlm.nih.gov/39163973/ DOI: 10.1016/j.tjnut.2024.08.011
tissue_or_cell_type
Whole-body amino-acid metabolism
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 648–657
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized intake-order repeated-measures experiment in five young men · source_derived_draft · unverified_draft
### wholewheat-lysine-availability The tested whole-wheat bread supplied lysine with an estimated 90% metabolic availability, while low lysine concentration still limited its protein quality. Plain language: A food can deliver most of its lysine efficiently yet contain too little lysine relative to other amino acids. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Whole-body amino-acid metabolism experimental_model: Randomized intake-order repeated-measures experiment in five young men limitations: Specific bread and small sample; metabolic availability is method-dependent and does not establish adequacy of all wheat-based diets. exposure: Lysine supplied by the tested whole-wheat bread; bread is a food matrix recorded in context, not a chemical-species entity. [tulnoor2025] Lysine from Whole Wheat Bread Consumed by Healthy Adult Males Has High Metabolic Availability When Assessed Using the Indicator Amino Acid Oxidation Method (2025). https://pubmed.ncbi.nlm.nih.gov/39163973/ DOI: 10.1016/j.tjnut.2024.08.011
Complete structured claim and evidence
In the Pakistani wheat-fortification trial, children receiving lysine-fortified flour gained more height and weight than controls over three months.
L-Lysine → Child height and weight gain source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Double-blind family feeding trial
limitations
Predominantly cereal-based, economically constrained diet; not proof of growth enhancement in lysine-replete children or isolated lysine deficiency in every participant.
organism
Homo sapiens
plain_language
Improving a lysine-poor staple was associated with better child growth in this dietary setting.
primary_references
[hussain2004] Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan (2004). https://pubmed.ncbi.nlm.nih.gov/15214256/ DOI: 10.1177/156482650402500202
tissue_or_cell_type
Whole-body growth
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 659–667
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind family feeding trial · source_derived_draft · unverified_draft
### fortification-child-growth In the Pakistani wheat-fortification trial, children receiving lysine-fortified flour gained more height and weight than controls over three months. Plain language: Improving a lysine-poor staple was associated with better child growth in this dietary setting. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Whole-body growth experimental_model: Double-blind family feeding trial limitations: Predominantly cereal-based, economically constrained diet; not proof of growth enhancement in lysine-replete children or isolated lysine deficiency in every participant. [hussain2004] Lysine fortification of wheat flour improves selected indices of the nutritional status of predominantly cereal-eating families in Pakistan (2004). https://pubmed.ncbi.nlm.nih.gov/15214256/ DOI: 10.1177/156482650402500202
Complete structured claim and evidence
The 1987 trial reported fewer recurrent HSV episodes with lysine than placebo among completers receiving 1 g three times daily for six months.
L-Lysine → Recurrent herpes simplex episodes source_derived_draftungraded
Experimental context and source evidence
experimental_model
Double-blind placebo-controlled multicenter clinical trial
limitations
52 completers; reported symptom/healing findings do not prove direct viral inhibition; intake is a studied regimen, not a recommendation.
organism
Homo sapiens
plain_language
One small trial favored lysine for recurrence prevention.
primary_references
[griffith1987] Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. (1987). https://pubmed.ncbi.nlm.nih.gov/3115841/ DOI: 10.1159/000248823
tissue_or_cell_type
Clinical mucocutaneous HSV outcomes
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 669–677
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind placebo-controlled multicenter clinical trial · source_derived_draft · unverified_draft
### hsv-recurrence-positive-trial The 1987 trial reported fewer recurrent HSV episodes with lysine than placebo among completers receiving 1 g three times daily for six months. Plain language: One small trial favored lysine for recurrence prevention. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Clinical mucocutaneous HSV outcomes experimental_model: Double-blind placebo-controlled multicenter clinical trial limitations: 52 completers; reported symptom/healing findings do not prove direct viral inhibition; intake is a studied regimen, not a recommendation. [griffith1987] Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. (1987). https://pubmed.ncbi.nlm.nih.gov/3115841/ DOI: 10.1159/000248823
Complete structured claim and evidence
The 1980 crossover trial found no overall reduction in herpes-labialis recurrence or healing time with 1 g daily lysine, despite more recurrence-free participants.
L-Lysine → Recurrent herpes simplex episodes source_derived_draftungraded
Experimental context and source evidence
experimental_model
Double-blind crossover clinical trial in 65 patients
limitations
Twelve-week treatment periods; outcome definition and regimen differ from the later positive trial.
organism
Homo sapiens
plain_language
The average recurrence and healing results were negative, although one secondary pattern favored treatment.
primary_references
[milman1980] Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. (1980). https://medicaljournalssweden.se/actadv/article/view/10630 DOI: 10.2340/00015555608587
tissue_or_cell_type
Lip herpes lesions
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 679–687
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind crossover clinical trial in 65 patients · source_derived_draft · unverified_draft
### hsv-recurrence-null-trial The 1980 crossover trial found no overall reduction in herpes-labialis recurrence or healing time with 1 g daily lysine, despite more recurrence-free participants. Plain language: The average recurrence and healing results were negative, although one secondary pattern favored treatment. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Lip herpes lesions experimental_model: Double-blind crossover clinical trial in 65 patients limitations: Twelve-week treatment periods; outcome definition and regimen differ from the later positive trial. [milman1980] Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. (1980). https://medicaljournalssweden.se/actadv/article/view/10630 DOI: 10.2340/00015555608587
Complete structured claim and evidence
Syrian wheat fortification reduced trait-anxiety scores in men, with benefit concentrated in those with high baseline anxiety; women showed no trait-anxiety effect.
L-Lysine → Trait anxiety source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Three-month randomized household trial
limitations
Dietary estimates, not individual biochemical diagnosis; one questionnaire; cannot establish treatment of anxiety disorders.
organism
Homo sapiens
plain_language
The anxiety result was subgroup-specific in a population with probable dietary inadequacy.
primary_references
[smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101
tissue_or_cell_type
Behavioral questionnaire outcome
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
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AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-month randomized household trial · source_derived_draft · unverified_draft
### syria-trait-anxiety Syrian wheat fortification reduced trait-anxiety scores in men, with benefit concentrated in those with high baseline anxiety; women showed no trait-anxiety effect. Plain language: The anxiety result was subgroup-specific in a population with probable dietary inadequacy. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Behavioral questionnaire outcome experimental_model: Three-month randomized household trial limitations: Dietary estimates, not individual biochemical diagnosis; one questionnaire; cannot establish treatment of anxiety disorders. [smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101
Complete structured claim and evidence
In the Syrian trial, lysine fortification reduced the cortisol response associated with blood drawing in females, without the same effect in males.
L-Lysine → Cortisol source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Randomized household fortification trial
limitations
Prestress baseline cortisol was not measured; not evidence of universal cortisol lowering.
organism
Homo sapiens
plain_language
The measured response to a specific stressor differed by sex.
primary_references
[smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101
tissue_or_cell_type
Blood cortisol under venipuncture stress
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 699–707
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized household fortification trial · source_derived_draft · unverified_draft
### syria-stress-cortisol In the Syrian trial, lysine fortification reduced the cortisol response associated with blood drawing in females, without the same effect in males. Plain language: The measured response to a specific stressor differed by sex. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Blood cortisol under venipuncture stress experimental_model: Randomized household fortification trial limitations: Prestress baseline cortisol was not measured; not evidence of universal cortisol lowering. [smriga2004] Lysine fortification reduces anxiety and lessens stress in family members in economically weak communities in Northwest Syria (2004). https://pmc.ncbi.nlm.nih.gov/articles/PMC420386/ DOI: 10.1073/pnas.0402550101
Complete structured claim and evidence
The Ghana trial found no significant lysine-placebo difference in trait-anxiety change or skin-conductance stress responses.
L-Lysine → Trait anxiety source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized placebo-controlled community trial using 1 g/day
limitations
Only a subset was at estimated dietary inadequacy risk; within-group improvement does not show treatment efficacy.
organism
Homo sapiens
plain_language
Questionnaire anxiety improved in both groups, without a lysine-specific difference.
primary_references
[ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834
tissue_or_cell_type
Behavioral questionnaires and skin conductance
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 709–717
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled community trial using 1 g/day · source_derived_draft · unverified_draft
### ghana-anxiety-null The Ghana trial found no significant lysine-placebo difference in trait-anxiety change or skin-conductance stress responses. Plain language: Questionnaire anxiety improved in both groups, without a lysine-specific difference. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Behavioral questionnaires and skin conductance experimental_model: Randomized placebo-controlled community trial using 1 g/day limitations: Only a subset was at estimated dietary inadequacy risk; within-group improvement does not show treatment efficacy. [ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834
Complete structured claim and evidence
In the Ghana trial, lysine supplementation was associated with fewer child diarrheal episodes and illness days than placebo.
L-Lysine → Child diarrheal morbidity source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized placebo-controlled community trial
limitations
Context-specific clinical result; does not establish receptor antagonism, intestinal repair mechanism, or broad infection prevention.
organism
Homo sapiens
plain_language
A benefit appeared for this child morbidity endpoint in the studied community.
primary_references
[ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834
tissue_or_cell_type
Gastrointestinal illness outcomes
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 719–727
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled community trial · source_derived_draft · unverified_draft
### ghana-child-diarrhea In the Ghana trial, lysine supplementation was associated with fewer child diarrheal episodes and illness days than placebo. Plain language: A benefit appeared for this child morbidity endpoint in the studied community. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Gastrointestinal illness outcomes experimental_model: Randomized placebo-controlled community trial limitations: Context-specific clinical result; does not establish receptor antagonism, intestinal repair mechanism, or broad infection prevention. [ghosh2010] Effect of lysine supplementation on health and morbidity in subjects belonging to poor peri-urban households in Accra, Ghana (2010). https://www.sciencedirect.com/science/article/pii/S0002916523019640 DOI: 10.3945/ajcn.2009.28834
Complete structured claim and evidence
One week of combined lysine and arginine reduced trait and stress-induced state anxiety in a randomized trial of 108 healthy Japanese adults.
L-Lysine → Trait and stress-induced state anxiety source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized double-blind placebo-controlled trial; 2.64 g/day of each amino acid
limitations
Short duration; no lysine-only arm; no established treatment effect for diagnosed anxiety disorders.
organism
Homo sapiens
plain_language
The tested mixture improved anxiety scores; the contribution of lysine alone is unknown.
primary_references
[smriga2007] Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans (2007). https://pubmed.ncbi.nlm.nih.gov/17510493/ DOI: 10.2220/biomedres.28.85
tissue_or_cell_type
Behavioral questionnaires
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 729–737
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial; 2.64 g/day of each amino acid · source_derived_draft · unverified_draft
### lysine-arginine-anxiety One week of combined lysine and arginine reduced trait and stress-induced state anxiety in a randomized trial of 108 healthy Japanese adults. Plain language: The tested mixture improved anxiety scores; the contribution of lysine alone is unknown. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Behavioral questionnaires experimental_model: Randomized double-blind placebo-controlled trial; 2.64 g/day of each amino acid limitations: Short duration; no lysine-only arm; no established treatment effect for diagnosed anxiety disorders. [smriga2007] Oral treatment with L-lysine and L-arginine reduces anxiety and basal cortisol levels in healthy humans (2007). https://pubmed.ncbi.nlm.nih.gov/17510493/ DOI: 10.2220/biomedres.28.85
Complete structured claim and evidence
In 29 high-trait-anxiety participants, lysine plus arginine increased stress-evoked ACTH, cortisol, adrenaline, and noradrenaline responses without changing heart-rate or blood-pressure responses.
L-Lysine → Neuroendocrine stress response source_derived_draftungraded
Experimental context and source evidence
experimental_model
Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress
limitations
Small combination trial; authors' proposed normalization is an interpretation, not a proven lysine-specific mechanism.
organism
Homo sapiens
plain_language
The mixture did not simply suppress all stress hormones.
primary_references
[jezova2005] Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety (2005). https://pubmed.ncbi.nlm.nih.gov/16117182/ DOI: 10.1080/10284150500162937
tissue_or_cell_type
Blood stress hormones and cardiovascular measurements
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 739–747
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress · source_derived_draft · unverified_draft
### lysine-arginine-stress-hormones In 29 high-trait-anxiety participants, lysine plus arginine increased stress-evoked ACTH, cortisol, adrenaline, and noradrenaline responses without changing heart-rate or blood-pressure responses. Plain language: The mixture did not simply suppress all stress hormones. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Blood stress hormones and cardiovascular measurements experimental_model: Ten-day randomized trial; 3 g/day of each amino acid, followed by public-speaking stress limitations: Small combination trial; authors' proposed normalization is an interpretation, not a proven lysine-specific mechanism. [jezova2005] Subchronic treatment with amino acid mixture of L-lysine and L-arginine modifies neuroendocrine activation during psychosocial stress in subjects with high trait anxiety (2005). https://pubmed.ncbi.nlm.nih.gov/16117182/ DOI: 10.1080/10284150500162937
Complete structured claim and evidence
In a short-term study of osteoporotic patients, lysine supplementation increased measured calcium absorption, whereas the valine and tryptophan comparators did not.
L-Lysine → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
Amino-acid comparator experiment using 800 mg/day in 45 osteoporotic patients
limitations
Short-term mineral handling; no fracture prevention or bone-density benefit established.
organism
Homo sapiens
plain_language
A small experiment found better absorption of calcium.
primary_references
[civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/
tissue_or_cell_type
Intestine
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 749–757
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Amino-acid comparator experiment using 800 mg/day in 45 osteoporotic patients · source_derived_draft · unverified_draft
### lysine-calcium-intestinal-study In a short-term study of osteoporotic patients, lysine supplementation increased measured calcium absorption, whereas the valine and tryptophan comparators did not. Plain language: A small experiment found better absorption of calcium. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Intestine experimental_model: Amino-acid comparator experiment using 800 mg/day in 45 osteoporotic patients limitations: Short-term mineral handling; no fracture prevention or bone-density benefit established. [civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/
Complete structured claim and evidence
In healthy women, adding 400 mg lysine to a calcium load blunted the subsequent rise in urinary calcium; this pattern was not reported for the osteoporotic group.
L-Lysine → Urinary calcium excretion source_derived_draftungraded
Experimental context and source evidence
experimental_model
Acute calcium-load comparison; healthy and osteoporotic women
limitations
Acute load response does not establish long-term calcium balance or skeletal outcomes.
organism
Homo sapiens
plain_language
Lysine altered short-term urinary calcium handling in one subgroup.
primary_references
[civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/
tissue_or_cell_type
Kidney and urine
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 759–767
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute calcium-load comparison; healthy and osteoporotic women · source_derived_draft · unverified_draft
### lysine-calcium-urinary-blunting In healthy women, adding 400 mg lysine to a calcium load blunted the subsequent rise in urinary calcium; this pattern was not reported for the osteoporotic group. Plain language: Lysine altered short-term urinary calcium handling in one subgroup. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney and urine experimental_model: Acute calcium-load comparison; healthy and osteoporotic women limitations: Acute load response does not establish long-term calcium balance or skeletal outcomes. [civitelli1992] Dietary L-lysine and calcium metabolism in humans (1992). https://pubmed.ncbi.nlm.nih.gov/1486246/
Complete structured claim and evidence
Adding lysine plus arginine to a low-protein diet produced only a nonsignificant calcium-absorption trend: 25.2% versus 22.3% with control, P=0.094.
L-Lysine → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
Six-day randomized crossover feeding study in 14 women
limitations
Combined amino acids; small sample; specifically low-protein background diet; no long-term skeletal endpoint.
organism
Homo sapiens
plain_language
The trial did not establish a statistically significant absorption benefit.
primary_references
[bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009
tissue_or_cell_type
Intestine
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 769–777
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-day randomized crossover feeding study in 14 women · source_derived_draft · unverified_draft
### dibasic-calcium-absorption-trend Adding lysine plus arginine to a low-protein diet produced only a nonsignificant calcium-absorption trend: 25.2% versus 22.3% with control, P=0.094. Plain language: The trial did not establish a statistically significant absorption benefit. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Intestine experimental_model: Six-day randomized crossover feeding study in 14 women limitations: Combined amino acids; small sample; specifically low-protein background diet; no long-term skeletal endpoint. [bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009
Complete structured claim and evidence
In the same crossover study, lysine plus arginine significantly increased urinary calcium compared with the low-protein control diet.
L-Lysine → Urinary calcium excretion source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized crossover feeding trial in 14 women
limitations
No lysine-only arm or demonstrated long-term calcium-balance effect.
organism
Homo sapiens
plain_language
More urinary calcium accompanied the mixture; it cannot by itself be read as either bone loss or better bone health.
primary_references
[bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009
tissue_or_cell_type
Kidney and urine
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 779–787
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized crossover feeding trial in 14 women · source_derived_draft · unverified_draft
### dibasic-urinary-calcium-increase In the same crossover study, lysine plus arginine significantly increased urinary calcium compared with the low-protein control diet. Plain language: More urinary calcium accompanied the mixture; it cannot by itself be read as either bone loss or better bone health. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney and urine experimental_model: Randomized crossover feeding trial in 14 women limitations: No lysine-only arm or demonstrated long-term calcium-balance effect. [bihuniak2014] Supplementing a low-protein diet with dibasic amino acids increases urinary calcium excretion in young women (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3927545/ DOI: 10.3945/jn.113.185009
Complete structured claim and evidence
A single case report associated oral lysine ingestion with Fanconi syndrome, severe tubulointerstitial nephritis, and subsequent chronic renal failure.
L-Lysine → Fanconi syndrome with tubulointerstitial nephritis source_derived_draftungraded
Experimental context and source evidence
experimental_model
Single clinical case report
limitations
No controlled comparison; susceptible individuals, coexposures, causality, and incidence cannot be resolved from this report.
organism
Homo sapiens
plain_language
This is a safety signal from one patient, not an established frequency or proof of cause.
primary_references
[lo1996] Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion (1996). https://pubmed.ncbi.nlm.nih.gov/8840955/ DOI: 10.1016/s0272-6386(96)90476-x
tissue_or_cell_type
Renal tubules and interstitium
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 789–797
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single clinical case report · source_derived_draft · unverified_draft
### lysine-renal-case-association A single case report associated oral lysine ingestion with Fanconi syndrome, severe tubulointerstitial nephritis, and subsequent chronic renal failure. Plain language: This is a safety signal from one patient, not an established frequency or proof of cause. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Renal tubules and interstitium experimental_model: Single clinical case report limitations: No controlled comparison; susceptible individuals, coexposures, causality, and incidence cannot be resolved from this report. [lo1996] Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion (1996). https://pubmed.ncbi.nlm.nih.gov/8840955/ DOI: 10.1016/s0272-6386(96)90476-x
Complete structured claim and evidence
After resistance exercise, 20 g highly glycated milk protein yielded lower six-hour plasma lysine availability than less glycated protein in young men; both protein arms also received 2 g free leucine.
Glycated milk protein → Postprandial plasma lysine availability source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo
limitations
Both protein arms included 2 g free leucine. Processing-related protein modification was manipulated; this was not a free-lysine supplementation or anti-glycation treatment trial.
organism
Homo sapiens
plain_language
Chemical modification of food protein changed how much lysine appeared in circulation.
primary_references
[vanlieshout2025] Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12308134/ DOI: 10.1016/j.tjnut.2025.05.032
tissue_or_cell_type
Blood after feeding
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 799–807
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo · source_derived_draft · unverified_draft
### milk-glycation-lysine-availability After resistance exercise, 20 g highly glycated milk protein yielded lower six-hour plasma lysine availability than less glycated protein in young men; both protein arms also received 2 g free leucine. Plain language: Chemical modification of food protein changed how much lysine appeared in circulation. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Blood after feeding experimental_model: Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo limitations: Both protein arms included 2 g free leucine. Processing-related protein modification was manipulated; this was not a free-lysine supplementation or anti-glycation treatment trial. [vanlieshout2025] Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12308134/ DOI: 10.1016/j.tjnut.2025.05.032
Complete structured claim and evidence
Six-hour postexercise muscle protein synthesis showed no significant difference among high-glycation milk protein plus 2 g free leucine, low-glycation milk protein plus 2 g free leucine, and noncaloric placebo groups (P=0.939).
Glycated milk protein → Muscle protein synthesis source_derived_draftungraded
Experimental context and source evidence
experimental_model
Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo
limitations
Both protein arms included 2 g free leucine. Acute muscle synthesis rates were 0.059, 0.061, and 0.061 percent per hour for low-glycation, high-glycation, and placebo groups respectively; no significant treatment separation (P=0.939). This null is not proof of equivalence or long-term irrelevance.
organism
Homo sapiens
plain_language
A changed blood nutrient measurement did not translate into a detectable synthesis difference in this experiment.
primary_references
[vanlieshout2025] Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12308134/ DOI: 10.1016/j.tjnut.2025.05.032
tissue_or_cell_type
Skeletal muscle
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 809–817
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo · source_derived_draft · unverified_draft
### milk-glycation-muscle-synthesis-null Six-hour postexercise muscle protein synthesis showed no significant difference among high-glycation milk protein plus 2 g free leucine, low-glycation milk protein plus 2 g free leucine, and noncaloric placebo groups (P=0.939). Plain language: A changed blood nutrient measurement did not translate into a detectable synthesis difference in this experiment. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Skeletal muscle experimental_model: Randomized parallel trial in 45 healthy young men comparing 20 g high-glycation milk protein plus 2 g free leucine, 20 g low-glycation milk protein plus 2 g free leucine, and noncaloric placebo limitations: Both protein arms included 2 g free leucine. Acute muscle synthesis rates were 0.059, 0.061, and 0.061 percent per hour for low-glycation, high-glycation, and placebo groups respectively; no significant treatment separation (P=0.939). This null is not proof of equivalence or long-term irrelevance. [vanlieshout2025] Milk Protein Glycation Compromises Postprandial Lysine Bioavailability but does not Modulate Postprandial Muscle Protein Synthesis Rates In Vivo in Males: A Double-blind, Randomized Parallel Trial (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12308134/ DOI: 10.1016/j.tjnut.2025.05.032
Complete structured claim and evidence
Lysine withdrawal suppressed mTORC1 activity in NSCLC cell lines, and lysine restoration reversed the suppression; GCN2 and AMPK contributed to this response.
L-Lysine → Mechanistic target of rapamycin complex 1 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Human NSCLC cell cultures including H1299, H460, and A549
limitations
Abrupt medium depletion; no direct lysine-binding sensor established; no supplementation benefit inferred for healthy humans.
organism
Homo sapiens
plain_language
These cultured cancer cells needed available lysine for full nutrient-and-growth-factor signaling.
primary_references
[jang2020] Lysine is required for growth factor-induced mTORC1 activation (2020). https://pubmed.ncbi.nlm.nih.gov/33008594/ DOI: 10.1016/j.bbrc.2020.09.100
tissue_or_cell_type
Cultured lung cancer cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 819–827
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human NSCLC cell cultures including H1299, H460, and A549 · source_derived_draft · unverified_draft
### lysine-deprivation-mtorc1 Lysine withdrawal suppressed mTORC1 activity in NSCLC cell lines, and lysine restoration reversed the suppression; GCN2 and AMPK contributed to this response. Plain language: These cultured cancer cells needed available lysine for full nutrient-and-growth-factor signaling. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Cultured lung cancer cells experimental_model: Human NSCLC cell cultures including H1299, H460, and A549 limitations: Abrupt medium depletion; no direct lysine-binding sensor established; no supplementation benefit inferred for healthy humans. [jang2020] Lysine is required for growth factor-induced mTORC1 activation (2020). https://pubmed.ncbi.nlm.nih.gov/33008594/ DOI: 10.1016/j.bbrc.2020.09.100
Complete structured claim and evidence
In noncancerous human cell lines, lysine withdrawal rapidly inhibited protein synthesis and stalled cell-cycle progression.
L-Lysine → Protein synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Live-cell imaging and perturbation experiments, primarily MCF10A and RPE-hTERT
limitations
Cell-line and acute-starvation context; response differs among amino acids and may vary across primary tissues.
organism
Homo sapiens
plain_language
Removing this required amino acid disrupted protein production and division in cultured cells.
primary_references
[rong2023] Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC11238304/ DOI: 10.1016/j.celrep.2023.113539
tissue_or_cell_type
Mammary epithelial and retinal pigment epithelial cell lines
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 829–837
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Live-cell imaging and perturbation experiments, primarily MCF10A and RPE-hTERT · source_derived_draft · unverified_draft
### lysine-deprivation-cellcycle In noncancerous human cell lines, lysine withdrawal rapidly inhibited protein synthesis and stalled cell-cycle progression. Plain language: Removing this required amino acid disrupted protein production and division in cultured cells. Condition category: nutrient_deficiency organism: Homo sapiens tissue_or_cell_type: Mammary epithelial and retinal pigment epithelial cell lines experimental_model: Live-cell imaging and perturbation experiments, primarily MCF10A and RPE-hTERT limitations: Cell-line and acute-starvation context; response differs among amino acids and may vary across primary tissues. [rong2023] Cells use multiple mechanisms for cell-cycle arrest upon withdrawal of individual amino acids (2023). https://pmc.ncbi.nlm.nih.gov/articles/PMC11238304/ DOI: 10.1016/j.celrep.2023.113539
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

A transport defect can limit lysine delivery despite its presence in food.

Condition: machinery_impairment · Pathogenic SLC7A7 variants causing lysinuric protein intolerance

Normal role: SLC7A7-SLC3A2 supports basolateral exchange of lysine and other cationic amino acids.

Recorded consequence: Pathogenic SLC7A7 variants impair epithelial dibasic-amino-acid transport in lysinuric protein intolerance.

Scope: Human inherited disease genetics and transport characterization

Saccharopine builds up when its production continues but its removal fails.

Condition: machinery_impairment · AASS SDH-domain impairment with LKR-domain flux retained

Normal role: AASS sequentially forms and then cleaves saccharopine; both catalytic domains must be considered.

Recorded consequence: Selective AASS saccharopine-dehydrogenase impairment while reductase activity persists causes saccharopine accumulation.

Scope: AASS-domain mutant worms and engineered mice

Accumulated saccharopine can harm mitochondria.

Condition: machinery_impairment · Saccharopine accumulation after selective AASS SDH impairment

Normal role: AASS dehydrogenase disposes of saccharopine produced by its reductase domain.

Recorded consequence: Excess saccharopine disrupts mitochondrial morphology and function in AASS-domain mutant models.

Scope: Genetic and suppression experiments in worms and mice

An enzyme block allows reactive lysine metabolites to accumulate.

Condition: machinery_impairment · Pathogenic ALDH7A1 variants impairing AASA dehydrogenase

Normal role: ALDH7A1 oxidizes AASA to aminoadipate, limiting the AASA/P6C pool.

Recorded consequence: ALDH7A1 deficiency reduces aldehyde clearance, increasing AASA and its equilibrium partner P6C.

Scope: Human patient biochemical and genetic evidence

A lysine metabolite can trap active vitamin B6.

Condition: machinery_impairment · P6C accumulation from ALDH7A1 impairment

Normal role: ALDH7A1 clears AASA while PLP serves as an available enzyme cofactor.

Recorded consequence: Accumulated P6C reacts with PLP through Knoevenagel condensation, reducing cofactor availability.

Scope: Chemical mechanism associated with human ALDH7A1 disease

A downstream enzyme defect leaves oxoadipate uncleared.

Condition: machinery_impairment · Biallelic DHTKD1 dysfunction

Normal role: DHTKD1-containing machinery converts 2-oxoadipate toward glutaryl-CoA.

Recorded consequence: DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal.

Scope: Two human patients and isotope-traced fibroblasts

Lysine loading can worsen a blocked breakdown pathway.

Condition: machinery_impairment · Gcdh knockout combined with high dietary lysine

Normal role: GCDH supports glutaryl-CoA conversion toward crotonyl-CoA.

Recorded consequence: High lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury.

Scope: High-lysine dietary challenge of Gcdh-knockout mice

An accumulated intermediate can react with a ketone body.

Condition: machinery_impairment · P6C accumulation in ALDH7A1 deficiency

Normal role: ALDH7A1 clearance limits accumulation of the P6C/AASA precursor pool.

Recorded consequence: P6C and acetoacetate form 2-OPP in chemical incubations including plasma.

Scope: Chemical incubations in aqueous solutions and human biological matrices

AASA measurement can reveal disturbed lysine breakdown.

Condition: biomarker_context · Clinical evaluation of pyridoxine-dependent epilepsy

Normal role: ALDH7A1 participates in normal AASA disposal; measurement is distinct from enzyme function.

Recorded consequence: Elevated AASA was observed in an 18-patient PDE cohort with ALDH7A1 investigation, including during pyridoxine treatment.

Scope: Human clinical cohort; plasma and urine assays

PLOD2 impairment changes collagen processing

Condition: machinery_impairment · Pathogenic PLOD2 variants.

Normal role: PLOD2 modifies collagen telopeptide lysines.

Recorded consequence: Abnormal cross-link pattern.

Scope: Bone collagen from a patient with compound-heterozygous PLOD2 variants.

LOX variants impair enzyme function

Condition: machinery_impairment · Ser280Arg or Ser348Arg substitution in expressed LOX.

Normal role: LOX helps initiate matrix cross-linking.

Recorded consequence: Reduced assay activity.

Scope: Human-family genetic study with expressed mutant-enzyme assays.

Lysine-limited protein utilization

Condition: nutrient_deficiency · Experimentally low lysine intake

Normal role: Adequate essential amino-acid availability supports protein utilization.

Recorded consequence: Greater indicator oxidation at limiting intake.

Scope: Controlled adult male feeding conditions.

Predominantly wheat-based dietary insufficiency

Condition: nutrient_deficiency · Low lysine density in a wheat-dominant diet

Normal role: Adequate lysine supports utilization of dietary protein.

Recorded consequence: Fortification group showed greater child growth.

Scope: Peshawar families in a three-month trial.

Probable lysine inadequacy and anxiety

Condition: nutrient_deficiency · Households selected for low dietary lysine density

Normal role: Nutritional adequacy may affect stress responses.

Recorded consequence: Male trait-anxiety scores improved.

Scope: Wheat-reliant Syrian communities.

Dietary lysine inadequacy and stress reactivity

Condition: nutrient_deficiency · Likely lysine-poor staple diet

Normal role: Adequate nutrition can support normal stress regulation.

Recorded consequence: Female venipuncture-associated cortisol response decreased.

Scope: Field measurements during blood collection.

Cell-culture lysine withdrawal suppresses mTORC1

Condition: nutrient_deficiency · Lysine removed from culture medium

Normal role: Available lysine permits full mTORC1 response to growth factors.

Recorded consequence: mTORC1 activity falls; repletion restores it.

Scope: NSCLC cell culture.

Acute lysine starvation and cell proliferation

Condition: nutrient_deficiency · Lysine removed from culture medium

Normal role: Lysine supplies protein synthesis needed for cell growth.

Recorded consequence: Translation inhibition accompanies stalled proliferation.

Scope: Two human epithelial cell-line models.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Consequences of AASS loss depend on the affected domainThe observations differ in experimental model, pathway segment or perturbation. They qualify an overgeneralized mechanism, rather than establishing that both experiments measured the same system.Read the recorded disagreement
Dietary fortification and a later community trial differ on anxietyBaseline diet, estimated inadequacy, initial anxiety, delivery, and setting differed. These are inconsistent effectiveness findings across contexts; differences are possible explanations, not demonstrated resolutions.Read the recorded disagreement
Lysine supplementation has inconsistent HSV trial resultsThese are inconsistent clinical findings, not logically contradictory molecular results. Regimen, duration, population, design, and endpoints differ. They cannot establish a dose threshold or explain the discrepancy.Read the recorded disagreement
Lysine-related interventions do not uniformly lower stress-hormone responsesThe trials differ in sex, diet, stressor, baseline anxiety, and arginine cointervention. Increased and decreased evoked hormones are not directly contradictory observations; neither supports a universal cortisol-lowering claim.Read the recorded disagreement
Precursor production versus completion of carnitine synthesisThe observations differ in experimental model, pathway segment or perturbation. They qualify an overgeneralized mechanism, rather than establishing that both experiments measured the same system.Read the recorded disagreement
Reduced lysine availability did not predict the measured muscle responseThese are distinct endpoints in the same experiment, not contradictory results. A nutrient-availability surrogate should not be converted into a demonstrated muscle outcome.Read the recorded disagreement
Relative cerebral saccharopine and pipecolate pathway importanceThe observations differ in experimental model, pathway segment or perturbation. They qualify an overgeneralized mechanism, rather than establishing that both experiments measured the same system.Read the recorded disagreement
Urinary calcium changes differ across intervention contextsAn acute calcium load with lysine differs from several days of lysine-plus-arginine on a low-protein diet. Urinary calcium alone does not settle net calcium balance or bone health.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Fortification studies primarily test improvement of likely limiting dietary lysine. Their results do not establish pharmacologic benefits of extra lysine in people whose total diet is already adequate.The research draft recorded this under 'Scope of nutritional inadequacy' with no reason given.
Food-derived lysine varies with total protein, protein source, energy, processing, and other amino acids. A mixed-diet association cannot identify an isolated lysine effect; availability and concentration are separate properties.The research draft recorded this under 'Diet and protein confounding' with no reason given.
The selected human trials do not directly demonstrate arginine competition, viral polymerase inhibition, or elimination of latent infection. Inconsistent trials do not justify a supplementation recommendation.The research draft recorded this under 'HSV mechanism and treatment' with no reason given.
These short experiments do not establish fracture reduction, durable bone-density improvement, or an overall long-term calcium-balance benefit. The 2014 calcium-absorption result is nonsignificant, despite some secondary summaries describing it as positive.The research draft recorded this under 'Calcium outcomes' with no reason given.
The renal case is hypothesis-generating. The selected primary studies cannot define a generally safe upper dose, long-term safety in all populations, or an adverse-event incidence. No dosage recommendation is offered.The research draft recorded this under 'Safety' with no reason given.
Do not alias a lysine residue in a histone, a methylated or acetylated lysine residue, a modifying enzyme, and free L-lysine. No direct histone-modification mechanism was established by the human supplementation papers selected here.The research draft recorded this under 'Histone lysine versus free lysine' with no reason given.
Protein glycation lowering lysine bioavailability is distinct from free lysine preventing tissue glycation. The cited feeding experiment supports the former only.The research draft recorded this under 'Anti-glycation claim' with no reason given.
Do not transfer antimicrobial or biomaterial properties of epsilon-poly-L-lysine or poly-D-lysine to monomeric nutritional L-lysine. No polymer claim is included without separately sourced evidence.The research draft recorded this under 'Polylysine and chemical forms' with no reason given.
GCN2/AMPK involvement in the selected NSCLC experiment does not identify a dedicated direct lysine-binding mTORC1 sensor or demonstrate a universal response in all tissues.The research draft recorded this under 'Direct lysine sensing' with no reason given.
No DOI was visible in the verified PubMed record for Civitelli 1992; null is retained instead of inventing one. Trial evidence is summarized as paraphrase, not verbatim publisher quotation.The research draft recorded this under 'Bibliographic limit' with no reason given.
What fraction of in-vivo adult human brain lysine oxidation uses each route?Human culture tracer evidence supports saccharopine but cannot alone establish all adult human brain fluxes.
Which enzyme supplies the initial alpha-deamination/transamination flux from L-lysine into P2C in each human tissue?The cited CRYM experiments characterize P2C reduction, not a complete experimentally identified human upstream enzyme chain.
How much carnitine biosynthetic flux is carried by SHMT1 versus SHMT2 in living humans?The 2024 biochemical activities establish catalytic capability; relative tissue flux is not directly quantified.
Does 2-OPP directly cause seizures or ongoing neurotoxicity in humans with ALDH7A1 deficiency?High external-dose zebrafish hyperactivity and patient accumulation do not establish the human causal contribution.
Whether additional oral lysine changes collagen cross-linking in lysine-replete humans is not established by these enzyme studies.Biochemical necessity and genetic impairment are not supplementation trials.
The catalog includes selected lysine post-translational modifications, not every lysine residue or every modifying enzyme in the human proteome.Residue-level coverage is explicitly incomplete; do not infer exhaustive mapping.
No human oral-lysine-to-histone-methylation causal chain is established in this extraction.Protein-bound lysine modification and free lysine availability are separate variables.
The effect of lysine supplementation on human microbiome cadaverine production and clinical outcomes is unresolved here.The included bacterial studies establish molecular reactions, not patient effects.
Lysine glycation, lysine-derived cross-links in elastin, SUMOylation and additional lysine acylations need separate residue- and tissue-specific curation.These broad areas were not exhaustively extracted; no universal causal arrows are invented.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

L-Lysine

The mechanisms

Human CAT1 transports L-lysine across the plasma membrane.

SLC7A9 associated with SLC3A1 mediates sodium-independent lysine exchange at the apical epithelial membrane.

SLC7A7-SLC3A2 exchanges intracellular cationic amino acids including lysine for extracellular neutral amino acids with sodium.

Reconstituted human SLC25A29 transports lysine by uniport and exchange, supporting lysine entry into the mitochondrial matrix.

KARS1 activates lysine with ATP, forming enzyme-bound lysyl-adenylate and releasing pyrophosphate.

After pyrophosphate release, KARS1 transfers activated lysine to the tRNA-Lys 3-prime end, forming lysyl-tRNA and AMP.

The AASS reductase domain condenses lysine with 2-oxoglutarate using NADPH to form saccharopine.

The AASS dehydrogenase domain oxidatively cleaves saccharopine, producing alpha-aminoadipate semialdehyde and glutamate with NAD+ reduction.

Alpha-aminoadipate semialdehyde interconverts with its cyclic Schiff base P6C.

ALDH7A1 oxidizes alpha-aminoadipate semialdehyde to alpha-aminoadipate using NAD+.

PLP-dependent AADAT transfers the amino group from aminoadipate to 2-oxoglutarate, generating 2-oxoadipate and glutamate.

DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation.

FAD-containing human GCDH dehydrogenates glutaryl-CoA through glutaconyl-CoA and decarboxylates it to crotonyl-CoA.

Human peroxisomal PIPOX oxidizes L-pipecolate to P6C.

Proteolysis releases free trimethyllysine from trimethyllysine-containing protein, providing a precursor for carnitine biosynthesis.

Human TMLHE hydroxylates free trimethyllysine to (2S,3S)-hydroxytrimethyllysine, coupled to 2-oxoglutarate oxidation.

Purified human SHMT1 cleaves hydroxytrimethyllysine into trimethylaminobutyraldehyde and glycine.

Purified human SHMT2 also cleaves hydroxytrimethyllysine, with lower measured catalytic efficiency than SHMT1.

Human ALDH9A1 oxidizes trimethylaminobutyraldehyde to gamma-butyrobetaine using NAD+.

BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron.

Pathogenic SLC7A7 variants impair epithelial dibasic-amino-acid transport in lysinuric protein intolerance.

Selective AASS saccharopine-dehydrogenase impairment while reductase activity persists causes saccharopine accumulation.

Excess saccharopine disrupts mitochondrial morphology and function in AASS-domain mutant models.

ALDH7A1 deficiency reduces aldehyde clearance, increasing AASA and its equilibrium partner P6C.

Accumulated P6C reacts with PLP through Knoevenagel condensation, reducing cofactor availability.

DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal.

High lysine intake in Gcdh-null mice increases glutarate accumulation and produces age-dependent brain injury.

P6C and acetoacetate form 2-OPP in chemical incubations including plasma.

Exposure to 10 mM 2-OPP increased zebrafish larval hyperactivity.

Elevated AASA was observed in an 18-patient PDE cohort with ALDH7A1 investigation, including during pyridoxine treatment.

CRYM ketimine reductase reduces P2C to L-pipecolate using reduced nicotinamide cofactors.

At the cytosolic 80S ribosome, the alpha-amino group of A-site lysyl-tRNA accepts the P-site nascent peptide, incorporating lysine into a peptide bond; the extended chain remains attached to the incoming tRNA.

Short-chain enoyl-CoA hydratase ECHS1 hydrates trans-crotonyl-CoA to (S)-3-hydroxybutyryl-CoA.

The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH.

Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules.

PLOD1 hydroxylates selected collagen-bound lysine residues to hydroxylysine.

PLOD2/LH2 hydroxylates collagen telopeptide lysines, influencing the subsequent cross-link pathway.

FKBP65 supports LH2/PLOD2 dimer formation in the tested collagen-producing cell systems.

PLOD3 hydroxylates peptidyl lysine using Fe(II), 2-oxoglutarate and oxygen.

Ascorbate supports sustained lysyl-hydroxylase activity; the enzyme can initially turn over without ascorbate.

COLGALT1 transfers galactose from UDP-galactose to collagen hydroxylysine.

Mn2+ supports COLGALT1 galactosyltransferase activity; Mg2+ gave lower activity in the reported assay.

PLOD3 transfers glucose from UDP-glucose onto galactosyl-hydroxylysine in collagen.

Lysyl oxidase converts suitable peptidyl lysines to allysine, producing ammonia and hydrogen peroxide.

Lysyl-oxidase activity can convert collagen hydroxylysine side chains to hydroxyallysine.

A protein-derived lysine-tyrosylquinone cofactor was identified in bovine aortic lysyl oxidase.

Dietary copper availability altered tendon lysyl-oxidase activation in the chick experiments.

Pathogenic PLOD2 variants were associated with telopeptide underhydroxylation and abnormal bone collagen cross-links.

Expressed LOX Ser280Arg and Ser348Arg variants had lower catalytic activity than wild-type LOX.

EP300 transfers an acetyl group from acetyl-CoA to a protein lysine side chain.

Human SIRT1 removes acetylation from histone H4 Lys16 in an NAD+-dependent reaction.

SETD7 transfers a methyl group from SAM to histone H3 Lys4 in peptide assays.

KDM1A/LSD1 oxidatively removes a methyl group from H3K4me2 through a flavin-dependent reaction.

KDM4A/JMJD2A can convert H3K9me3 to H3K9me2 using Fe(II), oxygen and 2-oxoglutarate.

DHPS transfers spermidine-derived aminobutyl onto eIF5A Lys50 to form deoxyhypusine.

DOHH hydroxylates deoxyhypusine-eIF5A to hypusine-eIF5A using its oxygen-activating diiron center.

Ubiquitin Gly76 can form an isopeptide bond to Lys48 of an adjacent ubiquitin in a chain.

The 26S proteasome degrades suitable Lys48-polyubiquitinated substrates; chain trimming permits continued substrate loading.

E. coli CadA converts lysine to cadaverine and CO2 while consuming a proton during acid stress.

E. coli CadB couples lysine uptake to cadaverine export in the Cad acid-response system.

In seven men receiving graded lysine intakes, indicator phenylalanine oxidation fell until a breakpoint and then remained approximately constant.

The tested whole-wheat bread supplied lysine with an estimated 90% metabolic availability, while low lysine concentration still limited its protein quality.

In the Pakistani wheat-fortification trial, children receiving lysine-fortified flour gained more height and weight than controls over three months.

The 1987 trial reported fewer recurrent HSV episodes with lysine than placebo among completers receiving 1 g three times daily for six months.

The 1980 crossover trial found no overall reduction in herpes-labialis recurrence or healing time with 1 g daily lysine, despite more recurrence-free participants.

Syrian wheat fortification reduced trait-anxiety scores in men, with benefit concentrated in those with high baseline anxiety; women showed no trait-anxiety effect.

In the Syrian trial, lysine fortification reduced the cortisol response associated with blood drawing in females, without the same effect in males.

The Ghana trial found no significant lysine-placebo difference in trait-anxiety change or skin-conductance stress responses.

In the Ghana trial, lysine supplementation was associated with fewer child diarrheal episodes and illness days than placebo.

One week of combined lysine and arginine reduced trait and stress-induced state anxiety in a randomized trial of 108 healthy Japanese adults.

In 29 high-trait-anxiety participants, lysine plus arginine increased stress-evoked ACTH, cortisol, adrenaline, and noradrenaline responses without changing heart-rate or blood-pressure responses.

In a short-term study of osteoporotic patients, lysine supplementation increased measured calcium absorption, whereas the valine and tryptophan comparators did not.

In healthy women, adding 400 mg lysine to a calcium load blunted the subsequent rise in urinary calcium; this pattern was not reported for the osteoporotic group.

Adding lysine plus arginine to a low-protein diet produced only a nonsignificant calcium-absorption trend: 25.2% versus 22.3% with control, P=0.094.

In the same crossover study, lysine plus arginine significantly increased urinary calcium compared with the low-protein control diet.

A single case report associated oral lysine ingestion with Fanconi syndrome, severe tubulointerstitial nephritis, and subsequent chronic renal failure.

After resistance exercise, 20 g highly glycated milk protein yielded lower six-hour plasma lysine availability than less glycated protein in young men; both protein arms also received 2 g free leucine.

Six-hour postexercise muscle protein synthesis showed no significant difference among high-glycation milk protein plus 2 g free leucine, low-glycation milk protein plus 2 g free leucine, and noncaloric placebo groups (P=0.939).