Nutrient chapter

L-Tyrosine

L-Tyrosine. Species, exposure and limitations are retained in each linked claim.

76 recorded mechanisms · 13 availability situations · 12 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.

Stable-isotope studies in 12 healthy adults demonstrated renal phenylalanine-to-tyrosine conversion and net renal tyrosine release.
Human phenylalanine hydroxylase / PAH → Human renal phenylalanine-to-tyrosine conversion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Arterial/renal-vein tracer sampling; comparison with a separate 12-person splanchnic study.
limitations
The organ flux measurement is direct; the assignment to PAH is the established reaction, not selective PAH perturbation in this study.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The kidney contributes to precursor production as well as filtration.
primary_references
The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10655515/ · DOI 10.1073/pnas.97.3.1242
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 20–26
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Arterial/renal-vein tracer sampling; comparison with a separate 12-person splanchnic study. · source_derived_draft · unverified_draft
## l-tyrosine-renal-production The kidney contributes to precursor production as well as filtration. Stable-isotope studies in 12 healthy adults demonstrated renal phenylalanine-to-tyrosine conversion and net renal tyrosine release. Model: Arterial/renal-vein tracer sampling; comparison with a separate 12-person splanchnic study. Limitations: The organ flux measurement is direct; the assignment to PAH is the established reaction, not selective PAH perturbation in this study. Evidence access: Primary abstract The kidney is an important site for in vivo phenylalanine-to-tyrosine conversion in adult humans: A metabolic role of the kidney. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10655515/ · DOI 10.1073/pnas.97.3.1242
Complete structured claim and evidence
Recombinant human TH1 bound natural BH4 with negative cooperativity; Ser40 phosphorylation increased apparent BH4 affinity.
Tetrahydrobiopterin / BH4 → Human tyrosine hydroxylase source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation.
limitations
These kinetic values are not blood targets or instructions to supplement BH4.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The cofactor response changes with enzyme regulation.
primary_references
Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10411647/ · DOI 10.1046/j.1432-1327.1999.00445.x
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 28–34
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation. · source_derived_draft · unverified_draft
## l-tyrosine-th-cofactor-regulation The cofactor response changes with enzyme regulation. Recombinant human TH1 bound natural BH4 with negative cooperativity; Ser40 phosphorylation increased apparent BH4 affinity. Model: Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation. Limitations: These kinetic values are not blood targets or instructions to supplement BH4. Evidence access: Primary abstract Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10411647/ · DOI 10.1046/j.1432-1327.1999.00445.x
Complete structured claim and evidence
Reconstituted human TH1 contained high-spin Fe(II); dehydration changed iron coordination and rehydration reversed the spectroscopic change.
Iron → Human tyrosine hydroxylase source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy.
limitations
A hydration-dependent structural change is not evidence that ordinary dehydration causes dopamine deficiency.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Iron participates in the enzyme itself, and its local environment matters.
primary_references
Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10499095/ · DOI 10.1007/s007750050308
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 36–42
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy. · source_derived_draft · unverified_draft
## l-tyrosine-th-iron Iron participates in the enzyme itself, and its local environment matters. Reconstituted human TH1 contained high-spin Fe(II); dehydration changed iron coordination and rehydration reversed the spectroscopic change. Model: Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy. Limitations: A hydration-dependent structural change is not evidence that ordinary dehydration causes dopamine deficiency. Evidence access: Primary abstract Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10499095/ · DOI 10.1007/s007750050308
Complete structured claim and evidence
Human PNMT transfers a methyl group from SAM to norepinephrine during epinephrine synthesis.
Human phenylethanolamine N-methyltransferase / PNMT → Epinephrine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human enzyme transition-state and inhibitor kinetics; structural analysis.
limitations
Shared SAM use does not prove that tyrosine supplementation drains folate, B12 or methionine.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A downstream branch uses a methyl donor from methionine metabolism.
primary_references
Transition-State Analogues of Phenylethanolamine N-Methyltransferase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32702980/ · DOI 10.1021/jacs.0c05446
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 44–50
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme transition-state and inhibitor kinetics; structural analysis. · source_derived_draft · unverified_draft
## l-tyrosine-pnmt-methyl A downstream branch uses a methyl donor from methionine metabolism. Human PNMT transfers a methyl group from SAM to norepinephrine during epinephrine synthesis. Model: Human enzyme transition-state and inhibitor kinetics; structural analysis. Limitations: Shared SAM use does not prove that tyrosine supplementation drains folate, B12 or methionine. Evidence access: Primary abstract Transition-State Analogues of Phenylethanolamine N-Methyltransferase. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32702980/ · DOI 10.1021/jacs.0c05446
Complete structured claim and evidence
Pathogenic CYB561 variants in four patients accompanied very low norepinephrine and epinephrine despite normal plasma DBH activity; impaired intravesicular ascorbate support was the proposed functional block.
Human cytochrome b561 / CYB561 → Human CYB561-dependent vesicular catecholamine synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Two human families; genetic analysis with supporting Cyb561 knockout mouse results.
limitations
The human defect and mouse corroboration are distinct evidence; ordinary dietary vitamin C deficiency was not the intervention.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A normal blood enzyme test can miss a cofactor problem inside a vesicle.
primary_references
Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 52–58
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Two human families; genetic analysis with supporting Cyb561 knockout mouse results. · source_derived_draft · unverified_draft
## l-tyrosine-cyb-vesicle A normal blood enzyme test can miss a cofactor problem inside a vesicle. Pathogenic CYB561 variants in four patients accompanied very low norepinephrine and epinephrine despite normal plasma DBH activity; impaired intravesicular ascorbate support was the proposed functional block. Model: Two human families; genetic analysis with supporting Cyb561 knockout mouse results. Limitations: The human defect and mouse corroboration are distinct evidence; ordinary dietary vitamin C deficiency was not the intervention. Evidence access: Primary abstract Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949
Complete structured claim and evidence
The CYB561-deficient patients responded favorably to L-dihydroxyphenylserine, a precursor that can be converted directly to norepinephrine.
L-Dihydroxyphenylserine / droxidopa → Human CYB561-dependent vesicular catecholamine synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Reported treatment responses in a small genetic case series.
limitations
This is a specific drug bypass, not evidence that tyrosine or ascorbate supplements correct the defect.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A downstream precursor can bypass a particular broken step.
primary_references
Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 60–66
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Reported treatment responses in a small genetic case series. · source_derived_draft · unverified_draft
## l-tyrosine-cyb-bypass A downstream precursor can bypass a particular broken step. The CYB561-deficient patients responded favorably to L-dihydroxyphenylserine, a precursor that can be converted directly to norepinephrine. Model: Reported treatment responses in a small genetic case series. Limitations: This is a specific drug bypass, not evidence that tyrosine or ascorbate supplements correct the defect. Evidence access: Primary abstract Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29343526/ · DOI 10.1161/CIRCRESAHA.117.311949
Complete structured claim and evidence
Human YARS1 ligates tyrosine to its cognate tRNA; the study separately examined the extracellular functions of this protein.
Human cytosolic tyrosyl-tRNA synthetase / YARS1 → Human cytosolic Tyr-tRNA Tyr source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; reaction description and experimental methods
experimental_model
Primary-paper description of YARS1 chemistry and human cellular/protein experiments.
limitations
The translation role is biochemical background in this paper; the main experiments concern extracellular signaling.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Tyrosine must be loaded onto tRNA to enter a growing protein.
primary_references
Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 68–74
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary-paper description of YARS1 chemistry and human cellular/protein experiments. · source_derived_draft · unverified_draft
## l-tyrosine-yars1-charging Tyrosine must be loaded onto tRNA to enter a growing protein. Human YARS1 ligates tyrosine to its cognate tRNA; the study separately examined the extracellular functions of this protein. Model: Primary-paper description of YARS1 chemistry and human cellular/protein experiments. Limitations: The translation role is biochemical background in this paper; the main experiments concern extracellular signaling. Evidence access: Primary full text; reaction description and experimental methods Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
Complete structured claim and evidence
Recombinant human YARS2 supported tyrosyl-tRNA aminoacylation; the F52L variant retained activity with abnormal kinetics.
Human mitochondrial tyrosyl-tRNA synthetase / YARS2 → Human mitochondrial Tyr-tRNA Tyr source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Wild-type and F52L human enzyme aminoacylation assays.
limitations
Retained activity does not mean normal function; this does not establish a tyrosine-rescue dose.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Mitochondria use a separate tyrosine-loading enzyme.
primary_references
Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20598274/ · DOI 10.1016/j.ajhg.2010.06.001
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 76–82
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Wild-type and F52L human enzyme aminoacylation assays. · source_derived_draft · unverified_draft
## l-tyrosine-yars2-charging Mitochondria use a separate tyrosine-loading enzyme. Recombinant human YARS2 supported tyrosyl-tRNA aminoacylation; the F52L variant retained activity with abnormal kinetics. Model: Wild-type and F52L human enzyme aminoacylation assays. Limitations: Retained activity does not mean normal function; this does not establish a tyrosine-rescue dose. Evidence access: Primary abstract Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20598274/ · DOI 10.1016/j.ajhg.2010.06.001
Complete structured claim and evidence
YARS2 F52L patient-derived myotubes had reduced synthesis of respiratory-chain subunits, with respiratory complex I, III and IV dysfunction in affected tissue.
Human mitochondrial tyrosyl-tRNA synthetase / YARS2 → Human YARS2-dependent mitochondrial translation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human MLASA families; skeletal muscle, fibroblasts and derived myotubes.
limitations
Fibroblasts were relatively spared, so the defect cannot be assigned one universal cellular severity.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A processing defect can cause an energy problem despite an available amino acid.
primary_references
Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20598274/ · DOI 10.1016/j.ajhg.2010.06.001
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 84–90
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MLASA families; skeletal muscle, fibroblasts and derived myotubes. · source_derived_draft · unverified_draft
## l-tyrosine-yars2-defect A processing defect can cause an energy problem despite an available amino acid. YARS2 F52L patient-derived myotubes had reduced synthesis of respiratory-chain subunits, with respiratory complex I, III and IV dysfunction in affected tissue. Model: Human MLASA families; skeletal muscle, fibroblasts and derived myotubes. Limitations: Fibroblasts were relatively spared, so the defect cannot be assigned one universal cellular severity. Evidence access: Primary abstract Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20598274/ · DOI 10.1016/j.ajhg.2010.06.001
Complete structured claim and evidence
The human YARS1 N-terminal fragment exhibited IL-8-like activity dependent on its differentiated ELR motif.
Human YARS1 N-terminal cytokine fragment → Human leukocyte chemotaxis induced by YARS1 fragments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human recombinant fragments and motif comparison with lower-eukaryote TyrRS.
limitations
This fragment is not free tyrosine, and its activity is not a supplement effect.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Cutting a protein can expose a signaling function.
primary_references
Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10438485/ · DOI 10.1074/jbc.274.33.23155
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 92–98
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant fragments and motif comparison with lower-eukaryote TyrRS. · source_derived_draft · unverified_draft
## l-tyrosine-yars-fragment Cutting a protein can expose a signaling function. The human YARS1 N-terminal fragment exhibited IL-8-like activity dependent on its differentiated ELR motif. Model: Human recombinant fragments and motif comparison with lower-eukaryote TyrRS. Limitations: This fragment is not free tyrosine, and its activity is not a supplement effect. Evidence access: Primary abstract Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10438485/ · DOI 10.1074/jbc.274.33.23155
Complete structured claim and evidence
A heptapeptide from the human YARS1 C-domain induced chemotaxis of mononuclear phagocytes and polymorphonuclear leukocytes.
Human YARS1 C-terminal EMAPII-like fragment → Human leukocyte chemotaxis induced by YARS1 fragments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
C-domain peptide assays and sequence-specific controls.
limitations
Other proteins with similar motifs were inactive in these assays; sequence similarity alone is insufficient.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A different part of the same protein has another signaling activity.
primary_references
Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10438485/ · DOI 10.1074/jbc.274.33.23155
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 100–106
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · C-domain peptide assays and sequence-specific controls. · source_derived_draft · unverified_draft
## l-tyrosine-yars-c-domain A different part of the same protein has another signaling activity. A heptapeptide from the human YARS1 C-domain induced chemotaxis of mononuclear phagocytes and polymorphonuclear leukocytes. Model: C-domain peptide assays and sequence-specific controls. Limitations: Other proteins with similar motifs were inactive in these assays; sequence similarity alone is insufficient. Evidence access: Primary abstract Highly differentiated motifs responsible for two cytokine activities of a split human tRNA synthetase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10438485/ · DOI 10.1074/jbc.274.33.23155
Complete structured claim and evidence
Extracellular YARS1 activated TLR2 signaling and inflammatory mediator release in human monocyte/macrophage preparations.
Human cytosolic tyrosyl-tRNA synthetase / YARS1 → Human Toll-like receptor 2 / TLR2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text and abstract
experimental_model
THP1 and peripheral-blood-derived macrophages; purified protein exposure.
limitations
This differs from intracellular charging and from assays of individual fragments.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A protein used for translation also signals outside cells.
primary_references
Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 108–114
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · THP1 and peripheral-blood-derived macrophages; purified protein exposure. · source_derived_draft · unverified_draft
## l-tyrosine-yrs-tlr2 A protein used for translation also signals outside cells. Extracellular YARS1 activated TLR2 signaling and inflammatory mediator release in human monocyte/macrophage preparations. Model: THP1 and peripheral-blood-derived macrophages; purified protein exposure. Limitations: This differs from intracellular charging and from assays of individual fragments. Evidence access: Primary full text and abstract Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
Complete structured claim and evidence
MMP cleavage of YARS1 increased TLR2 signaling, TNF secretion and chemotaxis relative to unprocessed YARS1.
Human matrix metalloproteinase 8 / MMP8 → Human YARS1 proteolysis-dependent inflammatory signaling source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text and abstract
experimental_model
Protein cleavage and macrophage assays; MMP7 and MMP8 among tested enzymes.
limitations
A proposed feed-forward inflammatory loop still requires in vivo testing.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Protease activity changes the strength of an extracellular signal.
primary_references
Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 116–122
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Protein cleavage and macrophage assays; MMP7 and MMP8 among tested enzymes. · source_derived_draft · unverified_draft
## l-tyrosine-yrs-proteolysis Protease activity changes the strength of an extracellular signal. MMP cleavage of YARS1 increased TLR2 signaling, TNF secretion and chemotaxis relative to unprocessed YARS1. Model: Protein cleavage and macrophage assays; MMP7 and MMP8 among tested enzymes. Limitations: A proposed feed-forward inflammatory loop still requires in vivo testing. Evidence access: Primary full text and abstract Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
Complete structured claim and evidence
At 0.5 millimolar in the substrate preincubation assay, tyrosine inhibited MMP8 cleavage of YARS1 but did not inhibit MMP7 cleavage.
L-Tyrosine → Human MMP8 cleavage of YARS1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; substrate/product cleavage methods and results
experimental_model
30-minute substrate preincubation at 22 degrees C; subsequent recombinant-enzyme cleavage assay.
limitations
This is not demonstrated inhibition of MMP8 generally or a clinical anti-inflammatory effect.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The amino acid can alter how one protease handles its loading enzyme.
primary_references
Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 124–130
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 30-minute substrate preincubation at 22 degrees C; subsequent recombinant-enzyme cleavage assay. · source_derived_draft · unverified_draft
## l-tyrosine-tyrosine-cleavage The amino acid can alter how one protease handles its loading enzyme. At 0.5 millimolar in the substrate preincubation assay, tyrosine inhibited MMP8 cleavage of YARS1 but did not inhibit MMP7 cleavage. Model: 30-minute substrate preincubation at 22 degrees C; subsequent recombinant-enzyme cleavage assay. Limitations: This is not demonstrated inhibition of MMP8 generally or a clinical anti-inflammatory effect. Evidence access: Primary full text; substrate/product cleavage methods and results Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31771979/ · DOI 10.1074/jbc.RA119.010486
Complete structured claim and evidence
Human thyroglobulin cryo-EM and site-directed mutagenesis identified tyrosine donor-acceptor pairs supporting hormone formation in vitro.
Human thyroglobulin → Human thyroglobulin hormonogenic tyrosine pairs source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human TG expressed in HEK293T cells; cryo-EM and in vitro hormone assays.
limitations
This does not mean free tyrosine is directly iodinated into circulating thyroid hormone.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The thyroid uses selected tyrosines already built into a protein.
primary_references
The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 132–138
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TG expressed in HEK293T cells; cryo-EM and in vitro hormone assays. · source_derived_draft · unverified_draft
## l-tyrosine-tg-iodinated-pairs The thyroid uses selected tyrosines already built into a protein. Human thyroglobulin cryo-EM and site-directed mutagenesis identified tyrosine donor-acceptor pairs supporting hormone formation in vitro. Model: Human TG expressed in HEK293T cells; cryo-EM and in vitro hormone assays. Limitations: This does not mean free tyrosine is directly iodinated into circulating thyroid hormone. Evidence access: Primary abstract The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4
Complete structured claim and evidence
Mutational and engineered-scaffold experiments implicated tyrosine proximity, flexibility and solvent exposure in hormone formation.
Human thyroglobulin hormonogenic tyrosine pairs → Human thyroglobulin tyrosine proximity, flexibility and solvent exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human TG and engineered bacterial maltose-binding-protein hormone-production assays.
limitations
The engineered bacterial scaffold is an in vitro demonstration, not a physiological human alternative.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Having the building blocks is not enough; their arrangement matters.
primary_references
The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 140–146
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TG and engineered bacterial maltose-binding-protein hormone-production assays. · source_derived_draft · unverified_draft
## l-tyrosine-tg-geometry Having the building blocks is not enough; their arrangement matters. Mutational and engineered-scaffold experiments implicated tyrosine proximity, flexibility and solvent exposure in hormone formation. Model: Human TG and engineered bacterial maltose-binding-protein hormone-production assays. Limitations: The engineered bacterial scaffold is an in vitro demonstration, not a physiological human alternative. Evidence access: Primary abstract The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4
Complete structured claim and evidence
Purified recombinant human tyrosinase showed monophenolase activity with L-tyrosine, the initial hydroxylation step toward pigment.
Human tyrosinase / TYR → L-3,4-Dihydroxyphenylalanine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; Results and catalytic assays
experimental_model
Human intramelanosomal domain expressed in insect cells; activity assays.
limitations
Same metabolite identity as L-DOPA in catecholamine synthesis, but different enzyme and compartment.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A different enzyme uses the same amino acid for pigment chemistry.
primary_references
Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 148–154
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human intramelanosomal domain expressed in insect cells; activity assays. · source_derived_draft · unverified_draft
## l-tyrosine-tyr-dopa A different enzyme uses the same amino acid for pigment chemistry. Purified recombinant human tyrosinase showed monophenolase activity with L-tyrosine, the initial hydroxylation step toward pigment. Model: Human intramelanosomal domain expressed in insect cells; activity assays. Limitations: Same metabolite identity as L-DOPA in catecholamine synthesis, but different enzyme and compartment. Evidence access: Primary full text; Results and catalytic assays Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494
Complete structured claim and evidence
Recombinant human tyrosinase also showed diphenol oxidase activity with L-DOPA, supporting the next oxidation toward dopaquinone.
Human tyrosinase / TYR → Dopaquinone source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; Results and catalytic assays
experimental_model
Purified human enzyme; L-DOPA colorimetric assays.
limitations
A colorimetric enzyme rate does not establish whole-body melanin output.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The pigment route includes a separate oxidation step.
primary_references
Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 156–162
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme; L-DOPA colorimetric assays. · source_derived_draft · unverified_draft
## l-tyrosine-tyr-quinone The pigment route includes a separate oxidation step. Recombinant human tyrosinase also showed diphenol oxidase activity with L-DOPA, supporting the next oxidation toward dopaquinone. Model: Purified human enzyme; L-DOPA colorimetric assays. Limitations: A colorimetric enzyme rate does not establish whole-body melanin output. Evidence access: Primary full text; Results and catalytic assays Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494
Complete structured claim and evidence
Human TYR R422Q and R422W variants had lower activity and temperature sensitivity compared with wild type.
Human tyrosinase / TYR → Human TYR R422Q/R422W pigment-enzyme activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Purified human intramelanosomal domains expressed in insect cells.
limitations
These variants retain activity; they should not be conflated with all albinism variants.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Reduced pigment synthesis can reflect enzyme structure rather than low tyrosine.
primary_references
Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 164–170
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human intramelanosomal domains expressed in insect cells. · source_derived_draft · unverified_draft
## l-tyrosine-tyr-variants Reduced pigment synthesis can reflect enzyme structure rather than low tyrosine. Human TYR R422Q and R422W variants had lower activity and temperature sensitivity compared with wild type. Model: Purified human intramelanosomal domains expressed in insect cells. Limitations: These variants retain activity; they should not be conflated with all albinism variants. Evidence access: Primary abstract Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24392141/ · DOI 10.1371/journal.pone.0084494
Complete structured claim and evidence
Lysosomes isolated from human HEK293T cells with MFSD12 accumulated more labeled cysteine than lysosomes from MFSD12-knockout cells.
Human MFSD12 cysteine transport component → Human lysosomal cysteine import source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; Fig. 4 and transport methods
experimental_model
Human HEK293T isolated lysosomes; radiolabeled cysteine transport.
limitations
This is lysosomal import; the separate pigment-cell findings connect the same protein to melanosomes. Purified-protein sufficiency was not established.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Pigment-related machinery also handles another amino acid in non-pigmented cells.
primary_references
MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 172–178
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T isolated lysosomes; radiolabeled cysteine transport. · source_derived_draft · unverified_draft
## l-tyrosine-mfsd12-cysteine Pigment-related machinery also handles another amino acid in non-pigmented cells. Lysosomes isolated from human HEK293T cells with MFSD12 accumulated more labeled cysteine than lysosomes from MFSD12-knockout cells. Model: Human HEK293T isolated lysosomes; radiolabeled cysteine transport. Limitations: This is lysosomal import; the separate pigment-cell findings connect the same protein to melanosomes. Purified-protein sufficiency was not established. Evidence access: Primary full text; Fig. 4 and transport methods MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
Complete structured claim and evidence
MFSD12 loss in human SKMEL30 cells reduced melanosomal cystine and cellular cysteinyldopas.
Human MFSD12 cysteine transport component → Cysteinyldopa isomers, pheomelanin precursors source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text; Fig. 2d–f
experimental_model
Human SKMEL30 loss-of-function; analogous mouse experiments were separately reported.
limitations
Lysosomal storage and melanosomal pigment endpoints differ.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A missing transporter can redirect pigment chemistry even when precursors exist elsewhere.
primary_references
MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 180–186
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SKMEL30 loss-of-function; analogous mouse experiments were separately reported. · source_derived_draft · unverified_draft
## l-tyrosine-mfsd12-loss A missing transporter can redirect pigment chemistry even when precursors exist elsewhere. MFSD12 loss in human SKMEL30 cells reduced melanosomal cystine and cellular cysteinyldopas. Model: Human SKMEL30 loss-of-function; analogous mouse experiments were separately reported. Limitations: Lysosomal storage and melanosomal pigment endpoints differ. Evidence access: Primary full text; Fig. 2d–f MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
Complete structured claim and evidence
Human HEK293T lysosomes with and without MFSD12 accumulated labeled tyrosine similarly despite the cysteine transport deficit.
Human MFSD12 cysteine transport component → Human isolated-lysosome tyrosine uptake source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; Fig. 4d
experimental_model
Matched lysosome preparations; 500 nM radiolabeled tyrosine uptake.
limitations
This control does not identify the tyrosine transporter.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Sharing an organelle does not mean sharing its transport route.
primary_references
MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 188–194
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Matched lysosome preparations; 500 nM radiolabeled tyrosine uptake. · source_derived_draft · unverified_draft
## l-tyrosine-mfsd12-tyrosine-control Sharing an organelle does not mean sharing its transport route. Human HEK293T lysosomes with and without MFSD12 accumulated labeled tyrosine similarly despite the cysteine transport deficit. Model: Matched lysosome preparations; 500 nM radiolabeled tyrosine uptake. Limitations: This control does not identify the tyrosine transporter. Evidence access: Primary full text; Fig. 4d MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
Complete structured claim and evidence
Tyr knockout in mouse B16F10 cells increased melanosomal tyrosine about twofold without changing whole-cell tyrosine, while pigment intermediates were lost.
Mouse tyrosinase Tyr → Mouse melanosomal tyrosine concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text; Fig. 1d–e
experimental_model
Mouse B16F10 knockout; MelanoIP metabolomics.
limitations
Whole-cell and organelle concentrations are different measurements; this is not dietary deficiency.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A local buildup can accompany loss of the product it normally supplies.
primary_references
MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 196–202
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse B16F10 knockout; MelanoIP metabolomics. · source_derived_draft · unverified_draft
## l-tyrosine-mouse-tyr-compartment A local buildup can accompany loss of the product it normally supplies. Tyr knockout in mouse B16F10 cells increased melanosomal tyrosine about twofold without changing whole-cell tyrosine, while pigment intermediates were lost. Model: Mouse B16F10 knockout; MelanoIP metabolomics. Limitations: Whole-cell and organelle concentrations are different measurements; this is not dietary deficiency. Evidence access: Primary full text; Fig. 1d–e MFSD12 mediates the import of cysteine into melanosomes and lysosomes. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33208952/ · DOI 10.1038/s41586-020-2937-x
Complete structured claim and evidence
Recombinant human TAT catalyzed reversible tyrosine transamination, with the highest activity for the tyrosine/2-oxoglutarate substrate pair.
Human tyrosine aminotransferase / TAT → 4-Hydroxyphenylpyruvate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified full-length and truncated human enzyme expressed in E. coli.
limitations
A reversible enzyme assay is not a measurement of net in vivo flux.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Tyrosine breakdown begins by moving its amino group.
primary_references
The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 204–210
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified full-length and truncated human enzyme expressed in E. coli. · source_derived_draft · unverified_draft
## l-tyrosine-tat-carbon Tyrosine breakdown begins by moving its amino group. Recombinant human TAT catalyzed reversible tyrosine transamination, with the highest activity for the tyrosine/2-oxoglutarate substrate pair. Model: Purified full-length and truncated human enzyme expressed in E. coli. Limitations: A reversible enzyme assay is not a measurement of net in vivo flux. Evidence access: Primary abstract The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x
Complete structured claim and evidence
Human TAT is PLP dependent, with spectroscopic analysis of its cofactor-linked aldimine.
PLP → Human tyrosine aminotransferase / TAT source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human enzyme spectroscopy and kinetics.
limitations
Enzyme dependence does not establish dietary B6 limitation or that adding B6 treats TAT genetic deficiency.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The active B6 form participates in tyrosine breakdown.
primary_references
The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 212–218
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme spectroscopy and kinetics. · source_derived_draft · unverified_draft
## l-tyrosine-tat-b6 The active B6 form participates in tyrosine breakdown. Human TAT is PLP dependent, with spectroscopic analysis of its cofactor-linked aldimine. Model: Recombinant human enzyme spectroscopy and kinetics. Limitations: Enzyme dependence does not establish dietary B6 limitation or that adding B6 treats TAT genetic deficiency. Evidence access: Primary abstract The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x
Complete structured claim and evidence
Human TAT catalytic efficiency for tyrosine was about four orders of magnitude greater than for phenylalanine.
Human tyrosine aminotransferase / TAT → L-Phenylalanine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified human enzyme substrate comparison.
limitations
This finding does not support TAT as an effective substitute for deficient PAH.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Closely related amino acids are not interchangeable substrates.
primary_references
The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 220–226
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme substrate comparison. · source_derived_draft · unverified_draft
## l-tyrosine-tat-discrimination Closely related amino acids are not interchangeable substrates. Human TAT catalytic efficiency for tyrosine was about four orders of magnitude greater than for phenylalanine. Model: Purified human enzyme substrate comparison. Limitations: This finding does not support TAT as an effective substitute for deficient PAH. Evidence access: Primary abstract The narrow substrate specificity of human tyrosine aminotransferase--the enzyme deficient in tyrosinemia type II. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16640556/ · DOI 10.1111/j.1742-4658.2006.05202.x
Complete structured claim and evidence
Human HPD converts 4-hydroxyphenylpyruvate to homogentisate; substrate-binding-site mutations altered catalytic efficiency.
Human 4-hydroxyphenylpyruvate dioxygenase / HPD → Homogentisate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human enzyme mutagenesis, binding assays and structural simulation.
limitations
HPD must not be merged with HPDL, which has a different product.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The carbon skeleton passes through a separate oxygen-dependent enzyme.
primary_references
Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34047349/ · DOI 10.1042/BCJ20210005
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 228–234
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme mutagenesis, binding assays and structural simulation. · source_derived_draft · unverified_draft
## l-tyrosine-hpd-hga The carbon skeleton passes through a separate oxygen-dependent enzyme. Human HPD converts 4-hydroxyphenylpyruvate to homogentisate; substrate-binding-site mutations altered catalytic efficiency. Model: Human enzyme mutagenesis, binding assays and structural simulation. Limitations: HPD must not be merged with HPDL, which has a different product. Evidence access: Primary abstract Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34047349/ · DOI 10.1042/BCJ20210005
Complete structured claim and evidence
Human HGD catalyzes aromatic-ring cleavage during phenylalanine/tyrosine degradation; its structure contains a coordinated active-site iron ion.
Human homogentisate 1,2-dioxygenase / HGD → Homogentisate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human apo and iron-bound HGD crystallography.
limitations
The study is structural/enzymatic evidence, not a trial of iron supplementation.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Iron-dependent chemistry opens the aromatic ring for further breakdown.
primary_references
Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 236–242
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human apo and iron-bound HGD crystallography. · source_derived_draft · unverified_draft
## l-tyrosine-hgd-ring Iron-dependent chemistry opens the aromatic ring for further breakdown. Human HGD catalyzes aromatic-ring cleavage during phenylalanine/tyrosine degradation; its structure contains a coordinated active-site iron ion. Model: Human apo and iron-bound HGD crystallography. Limitations: The study is structural/enzymatic evidence, not a trial of iron supplementation. Evidence access: Primary abstract Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756
Complete structured claim and evidence
Alkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure.
Human homogentisate 1,2-dioxygenase / HGD → Human HGD-dependent homogentisate catabolism source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mapping disease-associated variants onto a human hexameric structure.
limitations
Structural mapping is not a functional assay for every variant or a universal severity predictor.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
How enzyme subunits fit together can affect metabolic disposal.
primary_references
Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 244–250
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mapping disease-associated variants onto a human hexameric structure. · source_derived_draft · unverified_draft
## l-tyrosine-hgd-variants How enzyme subunits fit together can affect metabolic disposal. Alkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure. Model: Mapping disease-associated variants onto a human hexameric structure. Limitations: Structural mapping is not a functional assay for every variant or a universal severity predictor. Evidence access: Primary abstract Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756
Complete structured claim and evidence
Human GSTZ1/MAAI catalyzes glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate.
Human maleylacetoacetate isomerase / GSTZ1 → Fumarylacetoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human MAAI crystal structure with glutathione and a substrate-mimicking sulfate ion.
limitations
Glutathione dependence does not imply stoichiometric depletion by ordinary tyrosine intake.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Glutathione has a catalytic role in nutrient breakdown as well as antioxidant roles.
primary_references
Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11327815/ · DOI 10.1021/bi002249z
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 252–258
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MAAI crystal structure with glutathione and a substrate-mimicking sulfate ion. · source_derived_draft · unverified_draft
## l-tyrosine-gst-isomerase Glutathione has a catalytic role in nutrient breakdown as well as antioxidant roles. Human GSTZ1/MAAI catalyzes glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate. Model: Human MAAI crystal structure with glutathione and a substrate-mimicking sulfate ion. Limitations: Glutathione dependence does not imply stoichiometric depletion by ordinary tyrosine intake. Evidence access: Primary abstract Crystal structure of maleylacetoacetate isomerase/glutathione transferase zeta reveals the molecular basis for its remarkable catalytic promiscuity. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11327815/ · DOI 10.1021/bi002249z
Complete structured claim and evidence
Mouse FAH structural and biochemical studies support cleavage of fumarylacetoacetate into fumarate and acetoacetate.
Mouse fumarylacetoacetate hydrolase / Fah → Fumarylacetoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse enzyme structure and physiological-product complexes.
limitations
The product-bound structure is mouse evidence; the separate human FAH gene/disease record is retained.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The pathway connects the amino-acid carbon skeleton to central metabolism.
primary_references
Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 260–266
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse enzyme structure and physiological-product complexes. · source_derived_draft · unverified_draft
## l-tyrosine-fah-products The pathway connects the amino-acid carbon skeleton to central metabolism. Mouse FAH structural and biochemical studies support cleavage of fumarylacetoacetate into fumarate and acetoacetate. Model: Mouse enzyme structure and physiological-product complexes. Limitations: The product-bound structure is mouse evidence; the separate human FAH gene/disease record is retained. Evidence access: Primary abstract Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1
Complete structured claim and evidence
The mouse FAH product complex places acetoacetate at a coordinated calcium ion near a Glu-His catalytic dyad.
Calcium ion → Mouse fumarylacetoacetate hydrolase / Fah source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse FAH X-ray structure; catalytic roles proposed from structure and mutagenesis.
limitations
This is not evidence that calcium supplementation restores FAH disease.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A metal participates in the terminal cleavage chemistry.
primary_references
Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 268–274
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse FAH X-ray structure; catalytic roles proposed from structure and mutagenesis. · source_derived_draft · unverified_draft
## l-tyrosine-fah-calcium A metal participates in the terminal cleavage chemistry. The mouse FAH product complex places acetoacetate at a coordinated calcium ion near a Glu-His catalytic dyad. Model: Mouse FAH X-ray structure; catalytic roles proposed from structure and mutagenesis. Limitations: This is not evidence that calcium supplementation restores FAH disease. Evidence access: Primary abstract Crystal structure and mechanism of a carbon-carbon bond hydrolase. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10508789/ · DOI 10.1016/s0969-2126(99)80170-1
Complete structured claim and evidence
In 13 unrelated hereditary-tyrosinemia-I families, FAH nonsense variants reduced transcript abundance and splice-site variants altered exon inclusion.
Human fumarylacetoacetate hydrolase / FAH → Human FAH transcript abundance and splicing source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human family genotyping and RNA analysis.
limitations
No strict genotype-severity relationship was established in this series.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The disease can arise before a functional enzyme is made.
primary_references
Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8557261/ · DOI 10.1007/BF00218833
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 276–282
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human family genotyping and RNA analysis. · source_derived_draft · unverified_draft
## l-tyrosine-fah-genetic The disease can arise before a functional enzyme is made. In 13 unrelated hereditary-tyrosinemia-I families, FAH nonsense variants reduced transcript abundance and splice-site variants altered exon inclusion. Model: Human family genotyping and RNA analysis. Limitations: No strict genotype-severity relationship was established in this series. Evidence access: Primary abstract Hereditary tyrosinemia type 1: novel missense, nonsense and splice consensus mutations in the human fumarylacetoacetate hydrolase gene; variability of the genotype-phenotype relationship. · 1996 · https://pubmed.ncbi.nlm.nih.gov/8557261/ · DOI 10.1007/BF00218833
Complete structured claim and evidence
Succinylacetone competitively inhibited purified human erythrocyte ALAD; the study reported submicromolar inhibition constants across human and animal preparations.
Succinylacetone → Human delta-aminolevulinate dehydratase / ALAD source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients.
limitations
The metabolite is associated with FAH deficiency, not demonstrated as a consequence of ordinary tyrosine supplements.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A blocked tyrosine pathway can interfere with heme production.
primary_references
Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 284–290
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients. · source_derived_draft · unverified_draft
## l-tyrosine-sa-alad A blocked tyrosine pathway can interfere with heme production. Succinylacetone competitively inhibited purified human erythrocyte ALAD; the study reported submicromolar inhibition constants across human and animal preparations. Model: Purified human erythrocyte enzyme plus mouse/bovine preparations; four affected patients. Limitations: The metabolite is associated with FAH deficiency, not demonstrated as a consequence of ordinary tyrosine supplements. Evidence access: Primary abstract Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809
Complete structured claim and evidence
Adding succinylacetone to avian hepatocytes reduced cellular heme and cytochrome P450 content.
Succinylacetone → Avian cultured-hepatocyte heme content source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cultured avian hepatocytes with direct metabolite exposure.
limitations
The cellular effect is avian; the human ALAD inhibition is recorded separately.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
One pathway blockage can reduce machinery used by other pathways.
primary_references
Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 292–298
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured avian hepatocytes with direct metabolite exposure. · source_derived_draft · unverified_draft
## l-tyrosine-sa-heme One pathway blockage can reduce machinery used by other pathways. Adding succinylacetone to avian hepatocytes reduced cellular heme and cytochrome P450 content. Model: Cultured avian hepatocytes with direct metabolite exposure. Limitations: The cellular effect is avian; the human ALAD inhibition is recorded separately. Evidence access: Primary abstract Hereditary tyrosinemia and the heme biosynthetic pathway. Profound inhibition of delta-aminolevulinic acid dehydratase activity by succinylacetone. · 1983 · https://pubmed.ncbi.nlm.nih.gov/6826727/ · DOI 10.1172/jci110809
Complete structured claim and evidence
Five days of 1 g/day chloral hydrate produced detectable dichloroacetate and urinary maleylacetone in healthy volunteers, consistent with inhibition of GSTZ1/MAAI-dependent tyrosine catabolism.
Chloral hydrate → Human maleylacetoacetate isomerase / GSTZ1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays.
limitations
Environmental-dose plasma DCA was undetectable; direct tissue-enzyme inhibition was inferred from metabolism, not biopsied. No low-dose equivalence is assumed.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A drug metabolite can interfere with an amino-acid disposal enzyme.
primary_references
Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25283137/ · DOI 10.1515/dmdi-2014-0015
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 300–306
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays. · source_derived_draft · unverified_draft
## l-tyrosine-chloral-gstz A drug metabolite can interfere with an amino-acid disposal enzyme. Five days of 1 g/day chloral hydrate produced detectable dichloroacetate and urinary maleylacetone in healthy volunteers, consistent with inhibition of GSTZ1/MAAI-dependent tyrosine catabolism. Model: Eight adults studied at clinical or environmental exposure levels; stable-isotope and metabolite assays. Limitations: Environmental-dose plasma DCA was undetectable; direct tissue-enzyme inhibition was inferred from metabolism, not biopsied. No low-dose equivalence is assumed. Evidence access: Primary abstract Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25283137/ · DOI 10.1515/dmdi-2014-0015
Complete structured claim and evidence
During nitisinone treatment in SONIA 2, urinary derivatives upstream of homogentisate increased and tracked treatment-associated hypertyrosinemia.
Nitisinone → Human alkaptonuria alternative urinary tyrosine metabolites source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
AKU trial samples at baseline, 24 and 48 months; 47 treated serum and 53 treated urine sample series, with untreated comparisons.
limitations
Metabolite associations do not identify every conjugating enzyme or prove the proposed clearance benefit. This exposure is pharmacological.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Blocking one step changes the distribution of metabolites across other routes.
primary_references
Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36295829/ · DOI 10.3390/metabo12100927
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 308–314
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · AKU trial samples at baseline, 24 and 48 months; 47 treated serum and 53 treated urine sample series, with untreated comparisons. · source_derived_draft · unverified_draft
## l-tyrosine-nitisinone-network Blocking one step changes the distribution of metabolites across other routes. During nitisinone treatment in SONIA 2, urinary derivatives upstream of homogentisate increased and tracked treatment-associated hypertyrosinemia. Model: AKU trial samples at baseline, 24 and 48 months; 47 treated serum and 53 treated urine sample series, with untreated comparisons. Limitations: Metabolite associations do not identify every conjugating enzyme or prove the proposed clearance benefit. This exposure is pharmacological. Evidence access: Primary abstract Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36295829/ · DOI 10.3390/metabo12100927
Complete structured claim and evidence
Recombinant chicken TTL incorporated radiolabeled tyrosine into mammalian brain alpha-tubulin in ATP/Mg-containing assays.
Chicken tubulin tyrosine ligase / Ttl → Bovine/porcine brain alpha-tubulin terminal tyrosine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; Methods and structure
experimental_model
Chicken enzyme with bovine/porcine tubulin; 400 micromolar ATP, 2.4 millimolar MgCl2 and 5 micromolar labeled tyrosine in activity assays.
limitations
Mixed-species reconstitution is not a human supplementation experiment. This is retyrosination, not tyrosine phosphorylation.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Tyrosine can be attached to an existing protein after translation.
primary_references
Structural basis of tubulin tyrosination by tubulin tyrosine ligase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23358242/ · DOI 10.1083/jcb.201211017
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 316–322
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chicken enzyme with bovine/porcine tubulin; 400 micromolar ATP, 2.4 millimolar MgCl2 and 5 micromolar labeled tyrosine in activity assays. · source_derived_draft · unverified_draft
## l-tyrosine-tubulin-retyrosination Tyrosine can be attached to an existing protein after translation. Recombinant chicken TTL incorporated radiolabeled tyrosine into mammalian brain alpha-tubulin in ATP/Mg-containing assays. Model: Chicken enzyme with bovine/porcine tubulin; 400 micromolar ATP, 2.4 millimolar MgCl2 and 5 micromolar labeled tyrosine in activity assays. Limitations: Mixed-species reconstitution is not a human supplementation experiment. This is retyrosination, not tyrosine phosphorylation. Evidence access: Primary full text; Methods and structure Structural basis of tubulin tyrosination by tubulin tyrosine ligase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23358242/ · DOI 10.1083/jcb.201211017
Complete structured claim and evidence
TTL recognized the curved tubulin dimer and its alpha-tubulin tail, discriminating between tubulin subunits and modification states.
Chicken tubulin tyrosine ligase / Ttl → Curved mammalian alpha/beta-tubulin dimer source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; Results
experimental_model
Chicken TTL structural reconstitution; tubulin-binding and activity comparisons.
limitations
Tubulin modification state controls access; the finding does not show dietary tyrosine is rate limiting.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The enzyme needs the correct protein shape and tail, not just free amino acid.
primary_references
Structural basis of tubulin tyrosination by tubulin tyrosine ligase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23358242/ · DOI 10.1083/jcb.201211017
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 324–330
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Chicken TTL structural reconstitution; tubulin-binding and activity comparisons. · source_derived_draft · unverified_draft
## l-tyrosine-tubulin-recognition The enzyme needs the correct protein shape and tail, not just free amino acid. TTL recognized the curved tubulin dimer and its alpha-tubulin tail, discriminating between tubulin subunits and modification states. Model: Chicken TTL structural reconstitution; tubulin-binding and activity comparisons. Limitations: Tubulin modification state controls access; the finding does not show dietary tyrosine is rate limiting. Evidence access: Primary full text; Results Structural basis of tubulin tyrosination by tubulin tyrosine ligase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23358242/ · DOI 10.1083/jcb.201211017
Complete structured claim and evidence
Gut bacterial tyrosine decarboxylase accepts tyrosine and also decarboxylates levodopa.
Enterococcus faecalis tyrosine decarboxylase → Tyramine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Gut bacterial enzyme/substrate characterization.
limitations
This is bacterial metabolism, distinct from human DDC. Tyramine exposure from food is not equivalent to free tyrosine intake.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Microbes can divert the amino acid into a bioactive amine.
primary_references
Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30659181/ · DOI 10.1038/s41467-019-08294-y
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 332–338
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Gut bacterial enzyme/substrate characterization. · source_derived_draft · unverified_draft
## l-tyrosine-bacterial-tyramine Microbes can divert the amino acid into a bioactive amine. Gut bacterial tyrosine decarboxylase accepts tyrosine and also decarboxylates levodopa. Model: Gut bacterial enzyme/substrate characterization. Limitations: This is bacterial metabolism, distinct from human DDC. Tyramine exposure from food is not equivalent to free tyrosine intake. Evidence access: Primary abstract Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30659181/ · DOI 10.1038/s41467-019-08294-y
Complete structured claim and evidence
Bacterial tyrosine decarboxylases converted levodopa to dopamine despite competing tyrosine or human decarboxylase inhibitors.
Enterococcus faecalis tyrosine decarboxylase → L-3,4-Dihydroxyphenylalanine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Bacterial enzyme experiments, human PD associations and proximal-intestinal rat studies.
limitations
Patient abundance associations and rat plasma effects are not proof that changing dietary tyrosine improves levodopa response.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Blocking the human enzyme may leave a microbial route active.
primary_references
Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30659181/ · DOI 10.1038/s41467-019-08294-y
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 340–346
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bacterial enzyme experiments, human PD associations and proximal-intestinal rat studies. · source_derived_draft · unverified_draft
## l-tyrosine-bacterial-drug Blocking the human enzyme may leave a microbial route active. Bacterial tyrosine decarboxylases converted levodopa to dopamine despite competing tyrosine or human decarboxylase inhibitors. Model: Bacterial enzyme experiments, human PD associations and proximal-intestinal rat studies. Limitations: Patient abundance associations and rat plasma effects are not proof that changing dietary tyrosine improves levodopa response. Evidence access: Primary abstract Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson's disease. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30659181/ · DOI 10.1038/s41467-019-08294-y
Complete structured claim and evidence
C. difficile fermented tyrosine to p-cresol; a p-cresol-deficient mutant had altered competitive fitness in co-culture and a mouse relapse model.
Clostridioides difficile tyrosine fermentation → Para-cresol / p-cresol source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
C. difficile parent/mutant strains, bacterial co-cultures and mouse infection model.
limitations
This does not quantify effects of a tyrosine supplement on human infection.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The same precursor can feed a microbial competition mechanism.
primary_references
Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30208103/ · DOI 10.1371/journal.ppat.1007191
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 348–354
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · C. difficile parent/mutant strains, bacterial co-cultures and mouse infection model. · source_derived_draft · unverified_draft
## l-tyrosine-microbial-cresol The same precursor can feed a microbial competition mechanism. C. difficile fermented tyrosine to p-cresol; a p-cresol-deficient mutant had altered competitive fitness in co-culture and a mouse relapse model. Model: C. difficile parent/mutant strains, bacterial co-cultures and mouse infection model. Limitations: This does not quantify effects of a tyrosine supplement on human infection. Evidence access: Primary abstract Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30208103/ · DOI 10.1371/journal.ppat.1007191
Complete structured claim and evidence
Exogenous p-cresol impaired susceptible Gram-negative bacterial membrane integrity; Gram-positive organisms were generally more tolerant.
Para-cresol / p-cresol → Gram-negative bacterial membrane integrity under p-cresol exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Defined bacterial exposure and membrane-integrity assays.
limitations
Susceptibility varies among organisms; no human systemic toxicity threshold is inferred.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A microbial breakdown product affects other community members.
primary_references
Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30208103/ · DOI 10.1371/journal.ppat.1007191
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 356–362
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Defined bacterial exposure and membrane-integrity assays. · source_derived_draft · unverified_draft
## l-tyrosine-cresol-membranes A microbial breakdown product affects other community members. Exogenous p-cresol impaired susceptible Gram-negative bacterial membrane integrity; Gram-positive organisms were generally more tolerant. Model: Defined bacterial exposure and membrane-integrity assays. Limitations: Susceptibility varies among organisms; no human systemic toxicity threshold is inferred. Evidence access: Primary abstract Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30208103/ · DOI 10.1371/journal.ppat.1007191
Complete structured claim and evidence
Loss of two C. difficile ABC-transporter genes was associated with lower tyrosine/phenylalanine uptake and p-cresol production, without a measurable growth or enterotoxin effect.
Clostridioides difficile aromatic amino-acid ABC transport system → Clostridioides difficile tyrosine fermentation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Genomic and phenotypic strain comparisons; convergent loss and laboratory emergence.
limitations
Association is retained as such; this is not direct human host transporter evidence.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Microbial access to a nutrient can change its products without stopping growth.
primary_references
Convergent Loss of ABC Transporter Genes From Clostridioides difficile Genomes Is Associated With Impaired Tyrosine Uptake and p-Cresol Production. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29867812/ · DOI 10.3389/fmicb.2018.00901
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 364–370
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Genomic and phenotypic strain comparisons; convergent loss and laboratory emergence. · source_derived_draft · unverified_draft
## l-tyrosine-bacterial-import Microbial access to a nutrient can change its products without stopping growth. Loss of two C. difficile ABC-transporter genes was associated with lower tyrosine/phenylalanine uptake and p-cresol production, without a measurable growth or enterotoxin effect. Model: Genomic and phenotypic strain comparisons; convergent loss and laboratory emergence. Limitations: Association is retained as such; this is not direct human host transporter evidence. Evidence access: Primary abstract Convergent Loss of ABC Transporter Genes From Clostridioides difficile Genomes Is Associated With Impaired Tyrosine Uptake and p-Cresol Production. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29867812/ · DOI 10.3389/fmicb.2018.00901
Complete structured claim and evidence
Higher predose urinary p-cresol sulfate was associated with a lower postdose acetaminophen sulfate-to-glucuronide ratio.
p-Cresol sulfate → Human urinary acetaminophen sulfate-to-glucuronide ratio source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human predose/postdose urine NMR after a standard acetaminophen dose.
limitations
The authors proposed competition for O-sulfonation; the association does not prove tyrosine intake depletes sulfate or increases drug toxicity.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Microbial metabolism can correlate with how a drug is processed.
primary_references
Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19667173/ · DOI 10.1073/pnas.0904489106
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 372–378
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human predose/postdose urine NMR after a standard acetaminophen dose. · source_derived_draft · unverified_draft
## l-tyrosine-cresol-drug-sulfation Microbial metabolism can correlate with how a drug is processed. Higher predose urinary p-cresol sulfate was associated with a lower postdose acetaminophen sulfate-to-glucuronide ratio. Model: Human predose/postdose urine NMR after a standard acetaminophen dose. Limitations: The authors proposed competition for O-sulfonation; the association does not prove tyrosine intake depletes sulfate or increases drug toxicity. Evidence access: Primary abstract Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19667173/ · DOI 10.1073/pnas.0904489106
Complete structured claim and evidence
A phenylalanine/tyrosine-free amino-acid injection mixture reduced tyrosine in rat prefrontal cortex and nucleus accumbens.
L-Tyrosine → Rat prefrontal/nucleus-accumbens tyrosine after combined precursor depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Rat amino-acid injection versus control mixture or saline; tissue HPLC.
limitations
Combined depletion is not isolated dietary tyrosine deficiency. Correction record: The 2018 correction (PMID 30094500) reports an error in norepinephrine standard concentrations used for HPLC calibration. The correction abstract was inspected, but full notice content was unavailable; its complete quantitative scope remains unverified. This collection uses the tyrosine depletion and dopamine-transient findings and does not reuse the original norepinephrine concentration result. https://pubmed.ncbi.nlm.nih.gov/30094500/
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Experimental precursor depletion can reduce local availability.
primary_references
Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26944052/ · DOI 10.1007/s00213-016-4259-0
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 380–386
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat amino-acid injection versus control mixture or saline; tissue HPLC. · source_derived_draft · unverified_draft
## l-tyrosine-rat-depletion Experimental precursor depletion can reduce local availability. A phenylalanine/tyrosine-free amino-acid injection mixture reduced tyrosine in rat prefrontal cortex and nucleus accumbens. Model: Rat amino-acid injection versus control mixture or saline; tissue HPLC. Limitations: Combined depletion is not isolated dietary tyrosine deficiency. Correction record: The 2018 correction (PMID 30094500) reports an error in norepinephrine standard concentrations used for HPLC calibration. The correction abstract was inspected, but full notice content was unavailable; its complete quantitative scope remains unverified. This collection uses the tyrosine depletion and dopamine-transient findings and does not reuse the original norepinephrine concentration result. https://pubmed.ncbi.nlm.nih.gov/30094500/ Evidence access: Primary abstract Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26944052/ · DOI 10.1007/s00213-016-4259-0
Complete structured claim and evidence
Combined phenylalanine/tyrosine depletion decreased dopamine-transient frequency without decreasing transient amplitude in freely moving rats.
L-Tyrosine → Rat nucleus-accumbens dopamine transient frequency source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Fast-scan cyclic voltammetry in a separate rat group from the tissue-content experiment.
limitations
The release endpoint is not a direct human measurement; the corrected norepinephrine endpoint is excluded. Correction record: The 2018 correction (PMID 30094500) reports an error in norepinephrine standard concentrations used for HPLC calibration. The correction abstract was inspected, but full notice content was unavailable; its complete quantitative scope remains unverified. This collection uses the tyrosine depletion and dopamine-transient findings and does not reuse the original norepinephrine concentration result. https://pubmed.ncbi.nlm.nih.gov/30094500/
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
Less precursor can change release dynamics without simply emptying all dopamine stores.
primary_references
Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26944052/ · DOI 10.1007/s00213-016-4259-0
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 388–394
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fast-scan cyclic voltammetry in a separate rat group from the tissue-content experiment. · source_derived_draft · unverified_draft
## l-tyrosine-rat-dopamine-transients Less precursor can change release dynamics without simply emptying all dopamine stores. Combined phenylalanine/tyrosine depletion decreased dopamine-transient frequency without decreasing transient amplitude in freely moving rats. Model: Fast-scan cyclic voltammetry in a separate rat group from the tissue-content experiment. Limitations: The release endpoint is not a direct human measurement; the corrected norepinephrine endpoint is excluded. Correction record: The 2018 correction (PMID 30094500) reports an error in norepinephrine standard concentrations used for HPLC calibration. The correction abstract was inspected, but full notice content was unavailable; its complete quantitative scope remains unverified. This collection uses the tyrosine depletion and dopamine-transient findings and does not reuse the original norepinephrine concentration result. https://pubmed.ncbi.nlm.nih.gov/30094500/ Evidence access: Primary abstract Acute phenylalanine/tyrosine depletion of phasic dopamine in the rat brain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26944052/ · DOI 10.1007/s00213-016-4259-0
Complete structured claim and evidence
In 19 volunteers, tyrosine-containing food bars improved selected working-memory measures during repeated cold-water immersion relative to cold/placebo.
L-Tyrosine → Human working memory during experimental cold-water exposure source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Double-blind within-subject design; two 150 mg/kg doses, total 300 mg/kg; two 90-minute approximately 10-degree-C immersions.
limitations
This was a high experimental dose, not routine dietary exposure; dopamine mediation was not directly measured.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
A benefit was observed under a specific severe stressor.
primary_references
Tyrosine supplementation mitigates working memory decrements during cold exposure. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17585971/ · DOI 10.1016/j.physbeh.2007.05.003
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 396–402
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Double-blind within-subject design; two 150 mg/kg doses, total 300 mg/kg; two 90-minute approximately 10-degree-C immersions. · source_derived_draft · unverified_draft
## l-tyrosine-cold-performance A benefit was observed under a specific severe stressor. In 19 volunteers, tyrosine-containing food bars improved selected working-memory measures during repeated cold-water immersion relative to cold/placebo. Model: Double-blind within-subject design; two 150 mg/kg doses, total 300 mg/kg; two 90-minute approximately 10-degree-C immersions. Limitations: This was a high experimental dose, not routine dietary exposure; dopamine mediation was not directly measured. Evidence access: Primary abstract Tyrosine supplementation mitigates working memory decrements during cold exposure. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17585971/ · DOI 10.1016/j.physbeh.2007.05.003
Complete structured claim and evidence
In 17 older adults, 100, 150 and 200 mg/kg oral tyrosine produced dose-dependent plasma increases, larger than young-adult responses at the shared dose.
L-Tyrosine → Older-adult plasma tyrosine after acute dosing source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Double-blind randomized crossover; 17 younger adults as a 150 mg/kg comparison group.
limitations
Plasma concentration is not a measurement of synaptic dopamine or a universal intracellular threshold.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The same dose does not produce the same exposure at every age.
primary_references
Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29168741/ · DOI 10.3390/nu9121279
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 404–410
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Double-blind randomized crossover; 17 younger adults as a 150 mg/kg comparison group. · source_derived_draft · unverified_draft
## l-tyrosine-older-plasma The same dose does not produce the same exposure at every age. In 17 older adults, 100, 150 and 200 mg/kg oral tyrosine produced dose-dependent plasma increases, larger than young-adult responses at the shared dose. Model: Double-blind randomized crossover; 17 younger adults as a 150 mg/kg comparison group. Limitations: Plasma concentration is not a measurement of synaptic dopamine or a universal intracellular threshold. Evidence access: Primary abstract Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29168741/ · DOI 10.3390/nu9121279
Complete structured claim and evidence
Load-dependent working-memory performance declined at higher tyrosine doses, particularly in older adults with larger plasma responses.
L-Tyrosine → Older-adult load-dependent working memory after tyrosine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same acute 17-person dose-ranging crossover, with N-back testing at 90 minutes.
limitations
Small experimental study; it does not establish a general toxicity threshold or contradict a different cold-stress task.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
More precursor was not better in this experiment.
primary_references
Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29168741/ · DOI 10.3390/nu9121279
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 412–418
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same acute 17-person dose-ranging crossover, with N-back testing at 90 minutes. · source_derived_draft · unverified_draft
## l-tyrosine-older-performance More precursor was not better in this experiment. Load-dependent working-memory performance declined at higher tyrosine doses, particularly in older adults with larger plasma responses. Model: Same acute 17-person dose-ranging crossover, with N-back testing at 90 minutes. Limitations: Small experimental study; it does not establish a general toxicity threshold or contradict a different cold-stress task. Evidence access: Primary abstract Dose-Dependent Effects of Oral Tyrosine Administration on Plasma Tyrosine Levels and Cognition in Aging. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29168741/ · DOI 10.3390/nu9121279
Complete structured claim and evidence
In a randomized double-blind trial of 70 healthy volunteers, 2 g tyrosine worsened cognitive flexibility under the high-load condition.
L-Tyrosine → Human cognitive flexibility after high cognitive load source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Tyrosine versus cellulose, high/low cognitive load and Wisconsin Card Sorting Test.
limitations
Physiological stress markers were not measured; catecholamine mediation remained unmeasured.
nutrient_topic
L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
plain_language
The effect depends on the task and the kind of stress.
primary_references
Tyrosine negatively affects flexible-like behaviour under cognitively demanding conditions. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31521870/ · DOI 10.1016/j.jad.2019.09.031
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 420–426
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Tyrosine versus cellulose, high/low cognitive load and Wisconsin Card Sorting Test. · source_derived_draft · unverified_draft
## l-tyrosine-cognitive-load The effect depends on the task and the kind of stress. In a randomized double-blind trial of 70 healthy volunteers, 2 g tyrosine worsened cognitive flexibility under the high-load condition. Model: Tyrosine versus cellulose, high/low cognitive load and Wisconsin Card Sorting Test. Limitations: Physiological stress markers were not measured; catecholamine mediation remained unmeasured. Evidence access: Primary abstract Tyrosine negatively affects flexible-like behaviour under cognitively demanding conditions. · 2020 · https://pubmed.ncbi.nlm.nih.gov/31521870/ · DOI 10.1016/j.jad.2019.09.031
Complete structured claim and evidence
An infant treated for tyrosinemia type I developed growth failure, anorexia, lethargy and hypotonia with low phenylalanine and tyrosine during restriction; adding both amino acids reversed these manifestations without reversing cirrhosis.
L-Phenylalanine → Infant illness during combined phenylalanine and tyrosine restriction source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Single historical infant case with combined phenylalanine/tyrosine restriction and repletion.
limitations
Cannot attribute every manifestation to isolated phenylalanine deficiency or generalize a dose threshold.
nutrient_topic
L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
plain_language
Over-restricting these building blocks can create a new shortage problem.
primary_references
Phenylalanine-tyrosine deficiency syndrome as a complication of the management of hereditary tyrosinemia. · 1977 · https://pubmed.ncbi.nlm.nih.gov/835507/ · DOI 10.1093/ajcn/30.2.209
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 254–260
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Single historical infant case with combined phenylalanine/tyrosine restriction and repletion. · source_derived_draft · unverified_draft
## l-phenylalanine-combined-shortage Over-restricting these building blocks can create a new shortage problem. An infant treated for tyrosinemia type I developed growth failure, anorexia, lethargy and hypotonia with low phenylalanine and tyrosine during restriction; adding both amino acids reversed these manifestations without reversing cirrhosis. Model: Single historical infant case with combined phenylalanine/tyrosine restriction and repletion. Limitations: Cannot attribute every manifestation to isolated phenylalanine deficiency or generalize a dose threshold. Evidence access: Primary abstract Phenylalanine-tyrosine deficiency syndrome as a complication of the management of hereditary tyrosinemia. · 1977 · https://pubmed.ncbi.nlm.nih.gov/835507/ · DOI 10.1093/ajcn/30.2.209
Complete structured claim and evidence
PAH catalyzes phenylalanine hydroxylation to tyrosine using BH4, molecular oxygen and non-heme ferrous iron.
Human phenylalanine hydroxylase / PAH → L-Tyrosine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text; reaction background distinguished from new structural experiments
experimental_model
Human PAH structural study; established reaction described in the full-text introduction.
limitations
This record describes the established reaction, not a new dietary intervention or a human iron-deficiency threshold.
nutrient_topic
L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
plain_language
Making tyrosine requires a working enzyme and its chemical helpers.
primary_references
Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748
L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 14–20
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PAH structural study; established reaction described in the full-text introduction. · source_derived_draft · unverified_draft
## l-phenylalanine-pah-conversion Making tyrosine requires a working enzyme and its chemical helpers. PAH catalyzes phenylalanine hydroxylation to tyrosine using BH4, molecular oxygen and non-heme ferrous iron. Model: Human PAH structural study; established reaction described in the full-text introduction. Limitations: This record describes the established reaction, not a new dietary intervention or a human iron-deficiency threshold. Evidence access: Primary full text; reaction background distinguished from new structural experiments Structural basis for ligand-dependent dimerization of phenylalanine hydroxylase regulatory domain. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27049649/ · DOI 10.1038/srep23748
Complete structured claim and evidence
Human tyrosine hydroxylase catalyzes BH4-dependent tyrosine hydroxylation to L-DOPA, a downstream step in dopamine biosynthesis.
Human tyrosine hydroxylase → L-3,4-Dihydroxyphenylalanine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human TH variant study; established enzyme reaction described in the abstract.
limitations
This is a downstream connection, not evidence that oral phenylalanine predictably raises brain dopamine.
nutrient_topic
L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
plain_language
Producing tyrosine is only the first part of the route toward dopamine.
primary_references
Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38084654/ · DOI 10.1002/jimd.12690
L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 118–124
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TH variant study; established enzyme reaction described in the abstract. · source_derived_draft · unverified_draft
## l-phenylalanine-tyrosine-next-step Producing tyrosine is only the first part of the route toward dopamine. Human tyrosine hydroxylase catalyzes BH4-dependent tyrosine hydroxylation to L-DOPA, a downstream step in dopamine biosynthesis. Model: Human TH variant study; established enzyme reaction described in the abstract. Limitations: This is a downstream connection, not evidence that oral phenylalanine predictably raises brain dopamine. Evidence access: Primary abstract Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38084654/ · DOI 10.1002/jimd.12690
Complete structured claim and evidence
Human LAT1 coexpressed with human SLC3A2/4F2hc in Xenopus oocytes transported large neutral amino acids; extracellular substrates exchanged intracellular leucine and glutamine.
Human L-type amino acid transporter 1 / LAT1 / SLC7A5 → Human LAT1 neutral amino acid exchange source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human transporter proteins in frog oocytes; human T24-cell disulfide-linked complex also detected.
limitations
This is an exchange assay, not a direct human brain-uptake trial.
nutrient_topic
Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
plain_language
Transport depends on a partner protein and amino acids on both sides of the membrane.
primary_references
Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11557028/ · DOI 10.1016/s0005-2736(01)00384-4
Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 42–48
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human transporter proteins in frog oocytes; human T24-cell disulfide-linked complex also detected. · source_derived_draft · unverified_draft
## tryptophan-lat1-partner Transport depends on a partner protein and amino acids on both sides of the membrane. Human LAT1 coexpressed with human SLC3A2/4F2hc in Xenopus oocytes transported large neutral amino acids; extracellular substrates exchanged intracellular leucine and glutamine. Model: Human transporter proteins in frog oocytes; human T24-cell disulfide-linked complex also detected. Limitations: This is an exchange assay, not a direct human brain-uptake trial. Evidence access: Primary abstract Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11557028/ · DOI 10.1016/s0005-2736(01)00384-4
Complete structured claim and evidence
Human TAT1 expressed in Xenopus oocytes transported tryptophan, tyrosine, phenylalanine and L-DOPA independently of sodium.
Human TAT1 / SLC16A10 → L-Tryptophan source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human cloned transporter; expression strongest in kidney and intestine.
limitations
The paper proposes disease relevance; it does not establish TAT1 defects as the cause of blue diaper syndrome.
nutrient_topic
Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
plain_language
Tryptophan also has an aromatic-amino-acid transport route.
primary_references
The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11827462/ · DOI 10.1006/geno.2001.6678
transport_effect
raises An oocyte transport measurement, which reports the cell interior rising. TAT1's role at the basolateral membrane is efflux, which this record does not measure.
transport_pool
the expressing cell An oocyte transport measurement, which reports the cell interior rising. TAT1's role at the basolateral membrane is efflux, which this record does not measure.
Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 50–56
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human cloned transporter; expression strongest in kidney and intestine. · source_derived_draft · unverified_draft
## tryptophan-tat1-transport Tryptophan also has an aromatic-amino-acid transport route. Human TAT1 expressed in Xenopus oocytes transported tryptophan, tyrosine, phenylalanine and L-DOPA independently of sodium. Model: Human cloned transporter; expression strongest in kidney and intestine. Limitations: The paper proposes disease relevance; it does not establish TAT1 defects as the cause of blue diaper syndrome. Evidence access: Primary abstract The human T-type amino acid transporter-1: characterization, gene organization, and chromosomal location. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11827462/ · DOI 10.1006/geno.2001.6678
Complete structured claim and evidence
Reconstituted human LAT1 supported histidine antiport, including exchange with internal cysteine, tyrosine or glutamine; external histidine affinity exceeded internal affinity.
Human L-type amino acid transporter 1 / LAT1 / SLC7A5 → L-Histidine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human SiHa extracts and purified recombinant human LAT1 in proteoliposomes.
limitations
In-vitro exchange does not establish whole-body competition or supplement ratios.
nutrient_topic
L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Histidine
plain_language
The transporter exchanges substrates, so both sides of the membrane matter.
primary_references
LAT1 is the transport competent unit of the LAT1/CD98 heterodimeric amino acid transporter. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26256001/ · DOI 10.1016/j.biocel.2015.08.004
transport_effect
depends Recorded as antiport, including exchange with internal cysteine, tyrosine or glutamine.
transport_pool
the cytosol across the plasma membrane Recorded as antiport, including exchange with internal cysteine, tyrosine or glutamine.
L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 58–64
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SiHa extracts and purified recombinant human LAT1 in proteoliposomes. · source_derived_draft · unverified_draft
## histidine-lat1-exchange The transporter exchanges substrates, so both sides of the membrane matter. Reconstituted human LAT1 supported histidine antiport, including exchange with internal cysteine, tyrosine or glutamine; external histidine affinity exceeded internal affinity. Model: Human SiHa extracts and purified recombinant human LAT1 in proteoliposomes. Limitations: In-vitro exchange does not establish whole-body competition or supplement ratios. Evidence access: Primary abstract LAT1 is the transport competent unit of the LAT1/CD98 heterodimeric amino acid transporter. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26256001/ · DOI 10.1016/j.biocel.2015.08.004
Complete structured claim and evidence
In ten PKU patients, 300 mg/kg/day tyrosine transiently raised calculated brain tyrosine influx from 27% to 90% of normal, but it remained below 70% for half the sampled period.
L-Tyrosine → Calculated tyrosine brain influx in PKU source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Forty-eight-hour human study with tyrosine on day two and calculated transport estimates.
limitations
Brain influx was modeled, not directly measured; high phenylalanine and other competing amino acids remain part of the model.
nutrient_topic
L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
plain_language
A blood rise after supplementation need not provide steady predicted brain delivery.
primary_references
Tyrosine supplementation in phenylketonuria: diurnal blood tyrosine levels and presumptive brain influx of tyrosine and other large neutral amino acids. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11562623/ · DOI 10.1067/mpd.2001.117576
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 198–204
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Forty-eight-hour human study with tyrosine on day two and calculated transport estimates. · source_derived_draft · unverified_draft
## l-phenylalanine-tyrosine-brain-estimate A blood rise after supplementation need not provide steady predicted brain delivery. In ten PKU patients, 300 mg/kg/day tyrosine transiently raised calculated brain tyrosine influx from 27% to 90% of normal, but it remained below 70% for half the sampled period. Model: Forty-eight-hour human study with tyrosine on day two and calculated transport estimates. Limitations: Brain influx was modeled, not directly measured; high phenylalanine and other competing amino acids remain part of the model. Evidence access: Primary abstract Tyrosine supplementation in phenylketonuria: diurnal blood tyrosine levels and presumptive brain influx of tyrosine and other large neutral amino acids. · 2001 · https://pubmed.ncbi.nlm.nih.gov/11562623/ · DOI 10.1067/mpd.2001.117576
Complete structured claim and evidence
DNAJC12 interacted with aromatic amino-acid hydroxylases, including PAH, tyrosine hydroxylase and tryptophan hydroxylases.
Human chaperone DNAJC12 → Human phenylalanine hydroxylase / PAH source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human DNAJC12 deficiency study with functional interaction experiments.
limitations
Interaction does not imply identical effects in all tissues or rescue by extra substrate.
nutrient_topic
L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
plain_language
A shared chaperone supports several amino-acid processing enzymes.
primary_references
Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28132689/ · DOI 10.1016/j.ajhg.2017.01.002
L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 102–108
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human DNAJC12 deficiency study with functional interaction experiments. · source_derived_draft · unverified_draft
## l-phenylalanine-dnaj-chaperone A shared chaperone supports several amino-acid processing enzymes. DNAJC12 interacted with aromatic amino-acid hydroxylases, including PAH, tyrosine hydroxylase and tryptophan hydroxylases. Model: Human DNAJC12 deficiency study with functional interaction experiments. Limitations: Interaction does not imply identical effects in all tissues or rescue by extra substrate. Evidence access: Primary abstract Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28132689/ · DOI 10.1016/j.ajhg.2017.01.002
Complete structured claim and evidence
Expressed human DDC decarboxylated L-DOPA; added PLP enhanced the measured activity.
Human aromatic L-amino acid decarboxylase / DDC → Dopamine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human DDC expressed in monkey COS cells; enzyme assays
exposure
PLP addition to transfected COS-cell enzyme incubations.
limitations
An expression-system response is not proof that supplements increase brain monoamines.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Human DDC expressed in monkey COS cells
plain_language
B6 cofactor supports this monoamine-producing step.
primary_references
[sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
tissue_or_cell_type
COS-cell expression system
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 999–1009
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DDC expressed in monkey COS cells; enzyme assays · source_derived_draft · unverified_draft
### b6-neuro-ddc-dopamine Expressed human DDC decarboxylated L-DOPA; added PLP enhanced the measured activity. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6 cofactor supports this monoamine-producing step. organism: Human DDC expressed in monkey COS cells tissue_or_cell_type: COS-cell expression system experimental_model: Human DDC expressed in monkey COS cells; enzyme assays limitations: An expression-system response is not proof that supplements increase brain monoamines. exposure: PLP addition to transfected COS-cell enzyme incubations. [sumi-1990-ddc] Characterization of recombinant human aromatic L-amino acid decarboxylase expressed in COS cells (1990). https://doi.org/10.1111/j.1471-4159.1990.tb04601.x DOI: 10.1111/j.1471-4159.1990.tb04601.x
Complete structured claim and evidence
Human apoDDC has exposed active sites; PLP-titrated structures and kinetics support a cofactor-linked conformational transition.
PLP → Human aromatic L-amino acid decarboxylase / DDC source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human DDC crystallography and kinetics
exposure
Apoenzyme crystallization and varied crystal PLP concentrations.
limitations
The closed comparison included pig holoenzyme; proposed degradation consequences were not directly established.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Cofactor binding changes the enzyme structure.
primary_references
[giardina-2011-ddc] Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3251144/ DOI: 10.1073/pnas.1111456108
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1023–1033
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human DDC crystallography and kinetics · source_derived_draft · unverified_draft
### b6-neuro-ddc-plp-conformation Human apoDDC has exposed active sites; PLP-titrated structures and kinetics support a cofactor-linked conformational transition. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor binding changes the enzyme structure. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human DDC crystallography and kinetics limitations: The closed comparison included pig holoenzyme; proposed degradation consequences were not directly established. exposure: Apoenzyme crystallization and varied crystal PLP concentrations. [giardina-2011-ddc] Open conformation of human DOPA decarboxylase reveals the mechanism of PLP addition to Group II decarboxylases (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3251144/ DOI: 10.1073/pnas.1111456108
Complete structured claim and evidence
Human DBH is the copper-enzyme step converting dopamine to norepinephrine; the study resolved its catalytic-core architecture.
Human dopamine beta-hydroxylase / DBH → Norepinephrine source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Human DBH X-ray crystallography
exposure
Crystal structure at 2.9 angstrom resolution
limitations
Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human protein
plain_language
Copper is part of the enzyme that converts one neurotransmitter into another.
primary_references
[copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980
tissue_or_cell_type
Purified dimeric enzyme
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1079–1090
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human DBH X-ray crystallography · source_derived_draft · unverified_draft
### copper-dbh-neurotransmitter-step Human DBH is the copper-enzyme step converting dopamine to norepinephrine; the study resolved its catalytic-core architecture. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper is part of the enzyme that converts one neurotransmitter into another. organism: Human protein tissue_or_cell_type: Purified dimeric enzyme experimental_model: Human DBH X-ray crystallography limitations: Open and closed conformations were observed; the proposed catalytic alternation and fully occupied binuclear states require further evidence. Do not equate a structural model with proof of psychiatric effects from copper intake. exposure: Crystal structure at 2.9 angstrom resolution evidence_span: {"source_cache": "artifacts/copper-research/27152332.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09", "start_char": 0, "end_char": 1325, "text_sha256": "984a9036d5157e29cdef55d42201887d3ff43cf533185148ba4e3f5c143ced09"} [copper-p27152332] The crystal structure of human dopamine β-hydroxylase at 2.9 Å resolution. (2016). https://pubmed.ncbi.nlm.nih.gov/27152332/ DOI: 10.1126/sciadv.1500980
Complete structured claim and evidence
Tyrosinase copper loading was transient and inefficient in the Golgi; ATP7A supplied copper for reloading in melanosomes.
Mouse copper-transporting ATPase Atp7a → Copper loading of mouse tyrosinase source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"}
experimental_model
Mouse melanocyte localization and tyrosinase metallation experiments
exposure
ATP7A/BLOC-1-dependent localization
limitations
Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse
plain_language
The pigment enzyme needs copper at its final workplace, not just earlier during production.
primary_references
[copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163
tissue_or_cell_type
Golgi and melanosomes
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 988–999
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse melanocyte localization and tyrosinase metallation experiments · source_derived_draft · unverified_draft
### copper-atp7a-tyr-reloading Tyrosinase copper loading was transient and inefficient in the Golgi; ATP7A supplied copper for reloading in melanosomes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pigment enzyme needs copper at its final workplace, not just earlier during production. organism: Mouse tissue_or_cell_type: Golgi and melanosomes experimental_model: Mouse melanocyte localization and tyrosinase metallation experiments limitations: Cell-type-specific routing; not proof that every pigmentation change is dietary copper deficiency. exposure: ATP7A/BLOC-1-dependent localization evidence_span: {"source_cache": "artifacts/copper-research/18650808.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72", "start_char": 0, "end_char": 1518, "text_sha256": "939893c830f7922818ec3d5a9fa90d7c1779493cd8ad7a39df801d72eb255a72"} [copper-p18650808] Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. (2008). https://pubmed.ncbi.nlm.nih.gov/18650808/ DOI: 10.1038/nature07163
Complete structured claim and evidence
Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex.
Human IYD lacking N-terminal membrane anchor → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine.
limitations
Cofactor structure; no riboflavin restriction or supplementation study.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 702–714
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-fmn-binding Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: IYD uses the vitamin-B2-derived cofactor FMN to handle iodotyrosine. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: Cofactor structure; no riboflavin restriction or supplementation study. exposure: Human soluble IYD crystallized alone or with 3-iodo-L-tyrosine. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 14596, "end_char": 15366, "text_sha256": "5f3959109e358adaddae3ea78c716d16316c28f6fb4153ad5696bae7b1ed733e", "text_characters": 770, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays.
Human IYD lacking N-terminal membrane anchor → Iodide ion source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 11103, "end_char": 12723, "text_sha256": "726c34262182d49a45a4741a29a49ef70bf6d529c79d75cfbb0e9ea59ffd256b", "text_characters": 1620, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration
exposure
0–70 micromolar [125I]DIT; sodium dithionite supplies reducing equivalents.
limitations
Anchor-deleted enzyme and artificial reductant; does not identify the physiological electron donor.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens recombinant protein
plain_language
IYD recovers iodine from leftover iodinated tyrosine.
primary_references
[iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
tissue_or_cell_type
Purified soluble IYD
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 688–700
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration · source_derived_draft · unverified_draft
### iodine-syn-iyd-dit-salvage Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: IYD recovers iodine from leftover iodinated tyrosine. organism: Homo sapiens recombinant protein tissue_or_cell_type: Purified soluble IYD experimental_model: Recombinant human IYD lacking residues 1–31; crystallography, radiotracer kinetics and redox titration limitations: Anchor-deleted enzyme and artificial reductant; does not identify the physiological electron donor. exposure: 0–70 micromolar [125I]DIT; sodium dithionite supplies reducing equivalents. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/25395621.txt", "start_char": 11103, "end_char": 12723, "text_sha256": "726c34262182d49a45a4741a29a49ef70bf6d529c79d75cfbb0e9ea59ffd256b", "text_characters": 1620, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2015] A switch between one- and two-electron chemistry of the human flavoprotein iodotyrosine deiodinase is controlled by substrate. (2015). https://pubmed.ncbi.nlm.nih.gov/25395621/ DOI: 10.1074/jbc.m114.605964
Complete structured claim and evidence
The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro.
Human IYD patient variant proteins studied in 2008 → Iodotyrosine deiodination source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
Four selected patients from three unrelated families plus in-vitro mutant enzyme assays
exposure
Two missense variants and one three-base-pair deletion; no nutrient-restriction experiment.
limitations
Abstract does not provide exact variant residues or assay dose.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens proteins
plain_language
Genetic defects can disable iodine recycling.
primary_references
[iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
tissue_or_cell_type
In-vitro enzyme assays
trigger_kind
machinery_impairment Imported condition classification; unverified.
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 744–756
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four selected patients from three unrelated families plus in-vitro mutant enzyme assays · source_derived_draft · unverified_draft
### iodine-syn-iyd-mutant-activity The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Genetic defects can disable iodine recycling. organism: Homo sapiens proteins tissue_or_cell_type: In-vitro enzyme assays experimental_model: Four selected patients from three unrelated families plus in-vitro mutant enzyme assays limitations: Abstract does not provide exact variant residues or assay dose. exposure: Two missense variants and one three-base-pair deletion; no nutrient-restriction experiment. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/18434651.json", "json_field": "abstractText", "text_sha256": "f257956854445e268691cd3df1388ca16cea3f41320a48753df200a381c56431", "text_characters": 914, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-iyd2008] Mutations in the iodotyrosine deiodinase gene and hypothyroidism. (2008). https://pubmed.ncbi.nlm.nih.gov/18434651/ DOI: 10.1056/nejmoa0706819
Complete structured claim and evidence
HPDL produced 4-hydroxymandelate in human cells.
Human hydroxyphenylpyruvate dioxygenase-like protein / HPDL → 4-Hydroxymandelate / 4-HMA source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/34471290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956", "start_char": 0, "end_char": 1028, "text_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956"}
experimental_model
Oxygen-isotope metabolomics and enzyme perturbation
exposure
18O2 labeling and HPDL activity
limitations
Cellular pathway; no evidence that additional tyrosine treats every CoQ deficiency.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Human cell lines
plain_language
A separate enzyme helps make the head of the CoQ molecule.
primary_references
[coq10-p34471290] The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. (2021). https://pubmed.ncbi.nlm.nih.gov/34471290/ DOI: 10.1038/s41586-021-03865-w
tissue_or_cell_type
Tyrosine-derived CoQ head-group precursor
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 164–175
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oxygen-isotope metabolomics and enzyme perturbation · source_derived_draft · unverified_draft
### coq10-hpdl-hma HPDL produced 4-hydroxymandelate in human cells. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate enzyme helps make the head of the CoQ molecule. organism: Human cell lines tissue_or_cell_type: Tyrosine-derived CoQ head-group precursor experimental_model: Oxygen-isotope metabolomics and enzyme perturbation limitations: Cellular pathway; no evidence that additional tyrosine treats every CoQ deficiency. exposure: 18O2 labeling and HPDL activity evidence_span: {"source_cache": "artifacts/coq10-research/34471290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956", "start_char": 0, "end_char": 1028, "text_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956"} [coq10-p34471290] The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. (2021). https://pubmed.ncbi.nlm.nih.gov/34471290/ DOI: 10.1038/s41586-021-03865-w
Complete structured claim and evidence
Isotope tracing identified 4-hydroxymandelate as a CoQ10 head-group biosynthetic intermediate.
4-Hydroxymandelate / 4-HMA → Coenzyme Q aromatic head-group biosynthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/coq10-research/34471290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956", "start_char": 0, "end_char": 1028, "text_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956"}
experimental_model
Oxygen-isotope metabolomics and enzyme perturbation
exposure
18O2 labeling and HPDL activity
limitations
Cellular pathway; no evidence that additional tyrosine treats every CoQ deficiency.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Human cell lines
plain_language
The head group has its own supply route, separate from the lipid tail.
primary_references
[coq10-p34471290] The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. (2021). https://pubmed.ncbi.nlm.nih.gov/34471290/ DOI: 10.1038/s41586-021-03865-w
tissue_or_cell_type
Tyrosine-derived CoQ head-group precursor
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 177–188
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oxygen-isotope metabolomics and enzyme perturbation · source_derived_draft · unverified_draft
### coq10-hma-headgroup Isotope tracing identified 4-hydroxymandelate as a CoQ10 head-group biosynthetic intermediate. Condition category: normal nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The head group has its own supply route, separate from the lipid tail. organism: Human cell lines tissue_or_cell_type: Tyrosine-derived CoQ head-group precursor experimental_model: Oxygen-isotope metabolomics and enzyme perturbation limitations: Cellular pathway; no evidence that additional tyrosine treats every CoQ deficiency. exposure: 18O2 labeling and HPDL activity evidence_span: {"source_cache": "artifacts/coq10-research/34471290.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956", "start_char": 0, "end_char": 1028, "text_sha256": "a3cbcc69203ace49d0451e55c2d4040109e16facb575f4d66a0396d375ba8956"} [coq10-p34471290] The polar oxy-metabolome reveals the 4-hydroxymandelate CoQ10 synthesis pathway. (2021). https://pubmed.ncbi.nlm.nih.gov/34471290/ DOI: 10.1038/s41586-021-03865-w
Complete structured claim and evidence
A homozygous COQ2 variant caused severe impairment of CoQ10 synthesis in patient fibroblasts.
Human 4-hydroxybenzoate polyprenyltransferase / COQ2 → Coenzyme Q biosynthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coq10-research/16400613.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bd16a213ac563cf32b275cdee32ba3082e6c296cf9129e0930e2f96f0d2dc72a", "start_char": 0, "end_char": 1000, "text_sha256": "bd16a213ac563cf32b275cdee32ba3082e6c296cf9129e0930e2f96f0d2dc72a"}
experimental_model
Family sequencing and fibroblast tracer assays
exposure
Homozygous COQ2 missense variant
limitations
Rare primary deficiency; sequence numbering follows the original publication.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Human siblings
plain_language
Having the building blocks does not help if the enzyme that joins them is defective.
primary_references
[coq10-p16400613] A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/16400613/ DOI: 10.1086/500092
tissue_or_cell_type
CoQ synthesis
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 229–240
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Family sequencing and fibroblast tracer assays · source_derived_draft · unverified_draft
### coq10-coq2-loss A homozygous COQ2 variant caused severe impairment of CoQ10 synthesis in patient fibroblasts. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having the building blocks does not help if the enzyme that joins them is defective. organism: Human siblings tissue_or_cell_type: CoQ synthesis experimental_model: Family sequencing and fibroblast tracer assays limitations: Rare primary deficiency; sequence numbering follows the original publication. exposure: Homozygous COQ2 missense variant evidence_span: {"source_cache": "artifacts/coq10-research/16400613.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bd16a213ac563cf32b275cdee32ba3082e6c296cf9129e0930e2f96f0d2dc72a", "start_char": 0, "end_char": 1000, "text_sha256": "bd16a213ac563cf32b275cdee32ba3082e6c296cf9129e0930e2f96f0d2dc72a"} [coq10-p16400613] A mutation in para-hydroxybenzoate-polyprenyl transferase (COQ2) causes primary coenzyme Q10 deficiency. (2006). https://pubmed.ncbi.nlm.nih.gov/16400613/ DOI: 10.1086/500092
Complete structured claim and evidence
Resveratrol occupied the tyrosine active site in human TyrRS co-crystals and inhibited amino-acid activation with reported Ki 22 micromolar.
Resveratrol → Human cytosolic tyrosyl-tRNA synthetase / YARS1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified human enzyme and structure.
limitations
The bound ligand adopts a cis conformation; the authors propose conformational accommodation from predominantly trans solution. This is not proof of physiological bulk photoisomerization.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
A protein that normally charges tyrosine tRNA also senses this compound.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 286–292
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human enzyme and structure. · source_derived_draft · unverified_draft
## resveratrol-tyrrs-binding A protein that normally charges tyrosine tRNA also senses this compound. Resveratrol occupied the tyrosine active site in human TyrRS co-crystals and inhibited amino-acid activation with reported Ki 22 micromolar. Model: Purified human enzyme and structure. Limitations: The bound ligand adopts a cis conformation; the authors propose conformational accommodation from predominantly trans solution. This is not proof of physiological bulk photoisomerization. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
In the resveratrol study, human TyrRS stimulated NAD-dependent PARP1 auto-poly-ADP-ribosylation in biochemical experiments.
Human cytosolic tyrosyl-tRNA synthetase / YARS1 → Human PARP1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified-protein interaction/activation assays.
limitations
Greater PARylation need not imply greater net NAD stores.
nutrient_topic
Resveratrol collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Resveratrol
plain_language
This signaling step consumes a niacin-derived cofactor.
primary_references
A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 302–308
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-protein interaction/activation assays. · source_derived_draft · unverified_draft
## resveratrol-tyrrs-parp This signaling step consumes a niacin-derived cofactor. In the resveratrol study, human TyrRS stimulated NAD-dependent PARP1 auto-poly-ADP-ribosylation in biochemical experiments. Model: Purified-protein interaction/activation assays. Limitations: Greater PARylation need not imply greater net NAD stores. Evidence access: Primary full text A human tRNA synthetase is a potent PARP1-activating effector target for resveratrol. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25533949/ · DOI 10.1038/nature14028
Complete structured claim and evidence
The human COMT structure 3BWM includes bound magnesium alongside SAM and the catechol analog.
Human catechol O-methyltransferase / COMT → Mg2+ source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/chlorogenic_acid-research/3BWM.cif", "source_url": "https://files.rcsb.org/download/3BWM.cif", "locator": "Primary deposited structure 3BWM chemical-component loop; zero-based end-exclusive Unicode offsets", "file_sha256": "debe2736e6c5affecce595281fac469cd424ab6e91a5d908ec89d9460f60e4f6", "start_char": 11428, "end_char": 13476, "text_sha256": "98319e36f43f3fe147a2b9a2444809c31b0e14ae68e789fe3c1a8303fd8da8bc"}
experimental_model
Human soluble COMT crystallography and deposited structure 3BWM
exposure
SAM and 3,5-dinitrocatechol-bound crystals; deposited Mg ion
limitations
Structural cofactor connection, not a CGA-magnesium supplementation trial. Human and rat COMT specificity differs; deposition includes an inhibitor analog rather than CGA.
nutrient_topic
Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. · Chlorogenic acid / 5-O-caffeoylquinic acid
organism
Homo sapiens
plain_language
Magnesium is part of the measured enzyme complex; this does not prove that CGA depletes magnesium.
primary_references
[chlorogenic_acid-p18486144] Crystal structures of human 108V and 108M catechol O-methyltransferase. (2008). https://pubmed.ncbi.nlm.nih.gov/18486144/ DOI: 10.1016/j.jmb.2008.04.040
tissue_or_cell_type
Purified soluble COMT
Chlorogenic acid: metabolism, signaling and nutrient connections (2026-09-17) · lines 854–865
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human soluble COMT crystallography and deposited structure 3BWM · source_derived_draft · unverified_draft
### chlorogenic_acid-human-comt-mg The human COMT structure 3BWM includes bound magnesium alongside SAM and the catechol analog. Condition category: normal nutrient_topic: Chlorogenic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium is part of the measured enzyme complex; this does not prove that CGA depletes magnesium. organism: Homo sapiens tissue_or_cell_type: Purified soluble COMT experimental_model: Human soluble COMT crystallography and deposited structure 3BWM limitations: Structural cofactor connection, not a CGA-magnesium supplementation trial. Human and rat COMT specificity differs; deposition includes an inhibitor analog rather than CGA. exposure: SAM and 3,5-dinitrocatechol-bound crystals; deposited Mg ion evidence_span: {"source_cache": "artifacts/chlorogenic_acid-research/3BWM.cif", "source_url": "https://files.rcsb.org/download/3BWM.cif", "locator": "Primary deposited structure 3BWM chemical-component loop; zero-based end-exclusive Unicode offsets", "file_sha256": "debe2736e6c5affecce595281fac469cd424ab6e91a5d908ec89d9460f60e4f6", "start_char": 11428, "end_char": 13476, "text_sha256": "98319e36f43f3fe147a2b9a2444809c31b0e14ae68e789fe3c1a8303fd8da8bc"} [chlorogenic_acid-p18486144] Crystal structures of human 108V and 108M catechol O-methyltransferase. (2008). https://pubmed.ncbi.nlm.nih.gov/18486144/ DOI: 10.1016/j.jmb.2008.04.040
Complete structured claim and evidence
In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%.
Succinylacetone → Human thyroid peroxidase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_span
{"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}
experimental_model
CHO cells expressing human TPO; additional primary thyroid cultures
exposure
Succinylacetone; concentration not stated in abstract.
limitations
Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold.
nutrient_topic
Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
organism
Homo sapiens protein; Cricetulus griseus host cells
plain_language
Blocking heme production kept much of TPO from reaching the surface.
primary_references
[iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533
tissue_or_cell_type
CHO endoplasmic reticulum and cell surface
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 576–588
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CHO cells expressing human TPO; additional primary thyroid cultures · source_derived_draft · unverified_draft
### iodine-syn-heme-trafficking In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking heme production kept much of TPO from reaching the surface. organism: Homo sapiens protein; Cricetulus griseus host cells tissue_or_cell_type: CHO endoplasmic reticulum and cell surface experimental_model: CHO cells expressing human TPO; additional primary thyroid cultures limitations: Pharmacological heme synthesis perturbation; not evidence of a dietary iron threshold. exposure: Succinylacetone; concentration not stated in abstract. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/10187846.json", "json_field": "abstractText", "text_sha256": "97f8a86c7effd5754e2b61c65d769de9e86678a7398c5eb20a0e88ac49a8fdbb", "text_characters": 1855, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo1999] Role of heme in intracellular trafficking of thyroperoxidase and involvement of H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent heme binding. (1999). https://pubmed.ncbi.nlm.nih.gov/10187846/ DOI: 10.1074/jbc.274.15.10533
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
Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites.
Human diamine oxidase / AOC1 / DAO → Protein-derived topaquinone / TPQ cofactor source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/19764817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6", "start_char": 0, "end_char": 1343, "text_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6"}
experimental_model
Crystallography of recombinant human diamine oxidase and inhibitor complexes
exposure
Native structure and inhibitor binding
limitations
Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human AOC1 expressed in insect cells
plain_language
Histamine-processing machinery includes both a metal and a protein-derived cofactor.
primary_references
[copper-p19764817] Structure and inhibition of human diamine oxidase. (2009). https://pubmed.ncbi.nlm.nih.gov/19764817/ DOI: 10.1021/bi9014192
tissue_or_cell_type
Purified protein
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1014–1025
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography of recombinant human diamine oxidase and inhibitor complexes · source_derived_draft · unverified_draft
### copper-aoc1-copper-tpq Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Histamine-processing machinery includes both a metal and a protein-derived cofactor. organism: Human AOC1 expressed in insect cells tissue_or_cell_type: Purified protein experimental_model: Crystallography of recombinant human diamine oxidase and inhibitor complexes limitations: Copper/TPQ dependence is molecular evidence, not a trial of copper for histamine intolerance; DAO activity can have multiple determinants. exposure: Native structure and inhibitor binding evidence_span: {"source_cache": "artifacts/copper-research/19764817.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6", "start_char": 0, "end_char": 1343, "text_sha256": "9a01d0dba5caec8a33a77fdbe7190d7a05bdd6e691a570a890eb6b19d4c692b6"} [copper-p19764817] Structure and inhibition of human diamine oxidase. (2009). https://pubmed.ncbi.nlm.nih.gov/19764817/ DOI: 10.1021/bi9014192
Complete structured claim and evidence
Human RRM2 radical-center tyrosine mutations abolished the detectable stable radical and ribonucleotide-reductase activity in the tested assays.
Human ribonucleotide reductase small subunit RRM2 → Deoxyribonucleotide synthesis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"}
experimental_model
Mutagenesis, EPR and catalytic assays
exposure
Conserved tyrosine mutations around the diiron center
limitations
Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human RRM2 and RRM2B proteins
plain_language
DNA building-block synthesis needs a functioning iron/radical enzyme system.
primary_references
[iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273
tissue_or_cell_type
Ribonucleotide reductase small subunits
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1174–1185
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutagenesis, EPR and catalytic assays · source_derived_draft · unverified_draft
### iron-rrm2-iron-radical Human RRM2 radical-center tyrosine mutations abolished the detectable stable radical and ribonucleotide-reductase activity in the tested assays. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: DNA building-block synthesis needs a functioning iron/radical enzyme system. organism: Human RRM2 and RRM2B proteins tissue_or_cell_type: Ribonucleotide reductase small subunits experimental_model: Mutagenesis, EPR and catalytic assays limitations: Purified enzyme mechanisms; no recommendation to increase dietary iron for DNA synthesis. exposure: Conserved tyrosine mutations around the diiron center evidence_span: {"source_cache": "artifacts/iron-research/16373698.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc", "start_char": 0, "end_char": 1165, "text_sha256": "0d3e9b3d6c8961f94af38195eab5b0b3180c321da1c7ca75ae956036a60b16cc"} [iron-p16373698] A dityrosyl-diiron radical cofactor center is essential for human ribonucleotide reductases. (2005). https://pubmed.ncbi.nlm.nih.gov/16373698/ DOI: 10.1158/1535-7163.mct-05-0273
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.

Low combined precursor supply changes dopamine release dynamics

Condition: nutrient_deficiency · Injected amino-acid mixture omitting both precursors.

Normal role: Phenylalanine and tyrosine supply catecholamine precursors.

Recorded consequence: Lower regional tyrosine and fewer dopamine transients.

Scope: Rat brain experimental depletion.

Present tyrosine still needs a functioning mitochondrial loading enzyme

Condition: machinery_impairment · Pathogenic YARS2 F52L.

Normal role: YARS2 charges mitochondrial tRNA.

Recorded consequence: Reduced mitochondrial translation and respiratory function.

Scope: Human MLASA tissues and cells.

Vesicular cofactor handling can block catecholamine synthesis

Condition: machinery_impairment · Pathogenic CYB561 variants.

Normal role: CYB561 supports ascorbate-dependent secretory-vesicle chemistry.

Recorded consequence: Low norepinephrine/epinephrine despite normal plasma DBH activity; reported downstream drug bypass.

Scope: Human families with mouse corroboration.

A pigment enzyme defect is not a precursor shortage

Condition: machinery_impairment · R422Q or R422W variants.

Normal role: TYR catalyzes early pigment chemistry.

Recorded consequence: Reduced, temperature-dependent enzyme activity.

Scope: Purified human enzyme.

A local precursor surplus can coexist with failed pigment synthesis

Condition: machinery_impairment · Tyr knockout.

Normal role: Mouse Tyr consumes melanosomal tyrosine.

Recorded consequence: Local tyrosine accumulated while pigment intermediates disappeared.

Scope: Mouse B16F10 organelle profiling.

Cysteine delivery can limit a tyrosine-derived pigment branch

Condition: machinery_impairment · MFSD12 loss.

Normal role: MFSD12 supports organelle cysteine import.

Recorded consequence: Reduced cystine and cysteinyldopa formation.

Scope: Cell and organelle experiments.

Homogentisate disposal depends on enzyme assembly

Condition: machinery_impairment · Alkaptonuria-associated variants.

Normal role: HGD opens the aromatic ring.

Recorded consequence: Potential disruption at subunit interfaces.

Scope: Human structural disease-variant mapping.

A terminal pathway defect can affect heme metabolism

Condition: machinery_impairment · FAH defects and experimental succinylacetone exposure.

Normal role: FAH supports terminal tyrosine catabolism.

Recorded consequence: Human ALAD inhibition and lower heme in avian hepatocytes.

Scope: Human genetics, human enzyme assays and separately labelled avian cells.

Drug exposure can impair shared breakdown machinery

Condition: machinery_impairment · Repeated clinical chloral-hydrate exposure.

Normal role: GSTZ1 supports tyrosine catabolism and DCA handling.

Recorded consequence: Urinary maleylacetone increased.

Scope: Eight healthy adult volunteers.

Microbial transport affects downstream metabolite production

Condition: machinery_impairment · Loss of two ABC-transporter genes.

Normal role: Bacterial transport supplies aromatic amino acids for fermentation.

Recorded consequence: Lower precursor uptake and p-cresol production.

Scope: C. difficile strain comparisons.

High tyrosine during enzyme inhibition has a distinct metabolic context

Condition: biomarker_context · Nitisinone treatment in alkaptonuria.

Normal role: Catabolism and conjugation determine metabolite clearance.

Recorded consequence: Altered upstream urinary metabolites track hypertyrosinemia.

Scope: Human trial metabolomics.

Blood exposure differs with age and dose

Condition: biomarker_context · Acute 100–200 mg/kg experimental oral doses.

Normal role: Transport and clearance shape circulating levels.

Recorded consequence: Dose-dependent plasma increases in older adults.

Scope: Human dose-ranging study.

A microbial co-metabolite tracks drug-conjugation patterns

Condition: biomarker_context · High predose urinary p-cresol sulfate.

Normal role: Host conjugation processes microbial products and drugs.

Recorded consequence: Lower acetaminophen sulfate-to-glucuronide ratio.

Scope: Human urine metabolomics.

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.

Chlorogenic acid: metabolism, signaling and nutrient connections (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
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (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
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (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
Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (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
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (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
L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
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
L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (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.

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.

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-Tyrosine

The mechanisms

Stable-isotope studies in 12 healthy adults demonstrated renal phenylalanine-to-tyrosine conversion and net renal tyrosine release.

Recombinant human TH1 bound natural BH4 with negative cooperativity; Ser40 phosphorylation increased apparent BH4 affinity.

Reconstituted human TH1 contained high-spin Fe(II); dehydration changed iron coordination and rehydration reversed the spectroscopic change.

Human PNMT transfers a methyl group from SAM to norepinephrine during epinephrine synthesis.

Pathogenic CYB561 variants in four patients accompanied very low norepinephrine and epinephrine despite normal plasma DBH activity; impaired intravesicular ascorbate support was the proposed functional block.

The CYB561-deficient patients responded favorably to L-dihydroxyphenylserine, a precursor that can be converted directly to norepinephrine.

Human YARS1 ligates tyrosine to its cognate tRNA; the study separately examined the extracellular functions of this protein.

Recombinant human YARS2 supported tyrosyl-tRNA aminoacylation; the F52L variant retained activity with abnormal kinetics.

YARS2 F52L patient-derived myotubes had reduced synthesis of respiratory-chain subunits, with respiratory complex I, III and IV dysfunction in affected tissue.

The human YARS1 N-terminal fragment exhibited IL-8-like activity dependent on its differentiated ELR motif.

A heptapeptide from the human YARS1 C-domain induced chemotaxis of mononuclear phagocytes and polymorphonuclear leukocytes.

Extracellular YARS1 activated TLR2 signaling and inflammatory mediator release in human monocyte/macrophage preparations.

MMP cleavage of YARS1 increased TLR2 signaling, TNF secretion and chemotaxis relative to unprocessed YARS1.

At 0.5 millimolar in the substrate preincubation assay, tyrosine inhibited MMP8 cleavage of YARS1 but did not inhibit MMP7 cleavage.

Human thyroglobulin cryo-EM and site-directed mutagenesis identified tyrosine donor-acceptor pairs supporting hormone formation in vitro.

Mutational and engineered-scaffold experiments implicated tyrosine proximity, flexibility and solvent exposure in hormone formation.

Purified recombinant human tyrosinase showed monophenolase activity with L-tyrosine, the initial hydroxylation step toward pigment.

Recombinant human tyrosinase also showed diphenol oxidase activity with L-DOPA, supporting the next oxidation toward dopaquinone.

Human TYR R422Q and R422W variants had lower activity and temperature sensitivity compared with wild type.

Lysosomes isolated from human HEK293T cells with MFSD12 accumulated more labeled cysteine than lysosomes from MFSD12-knockout cells.

MFSD12 loss in human SKMEL30 cells reduced melanosomal cystine and cellular cysteinyldopas.

Human HEK293T lysosomes with and without MFSD12 accumulated labeled tyrosine similarly despite the cysteine transport deficit.

Tyr knockout in mouse B16F10 cells increased melanosomal tyrosine about twofold without changing whole-cell tyrosine, while pigment intermediates were lost.

Recombinant human TAT catalyzed reversible tyrosine transamination, with the highest activity for the tyrosine/2-oxoglutarate substrate pair.

Human TAT is PLP dependent, with spectroscopic analysis of its cofactor-linked aldimine.

Human TAT catalytic efficiency for tyrosine was about four orders of magnitude greater than for phenylalanine.

Human HPD converts 4-hydroxyphenylpyruvate to homogentisate; substrate-binding-site mutations altered catalytic efficiency.

Human HGD catalyzes aromatic-ring cleavage during phenylalanine/tyrosine degradation; its structure contains a coordinated active-site iron ion.

Alkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure.

Human GSTZ1/MAAI catalyzes glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate.

Mouse FAH structural and biochemical studies support cleavage of fumarylacetoacetate into fumarate and acetoacetate.

The mouse FAH product complex places acetoacetate at a coordinated calcium ion near a Glu-His catalytic dyad.

In 13 unrelated hereditary-tyrosinemia-I families, FAH nonsense variants reduced transcript abundance and splice-site variants altered exon inclusion.

Succinylacetone competitively inhibited purified human erythrocyte ALAD; the study reported submicromolar inhibition constants across human and animal preparations.

Adding succinylacetone to avian hepatocytes reduced cellular heme and cytochrome P450 content.

Five days of 1 g/day chloral hydrate produced detectable dichloroacetate and urinary maleylacetone in healthy volunteers, consistent with inhibition of GSTZ1/MAAI-dependent tyrosine catabolism.

During nitisinone treatment in SONIA 2, urinary derivatives upstream of homogentisate increased and tracked treatment-associated hypertyrosinemia.

Recombinant chicken TTL incorporated radiolabeled tyrosine into mammalian brain alpha-tubulin in ATP/Mg-containing assays.

TTL recognized the curved tubulin dimer and its alpha-tubulin tail, discriminating between tubulin subunits and modification states.

Gut bacterial tyrosine decarboxylase accepts tyrosine and also decarboxylates levodopa.

Bacterial tyrosine decarboxylases converted levodopa to dopamine despite competing tyrosine or human decarboxylase inhibitors.

C. difficile fermented tyrosine to p-cresol; a p-cresol-deficient mutant had altered competitive fitness in co-culture and a mouse relapse model.

Exogenous p-cresol impaired susceptible Gram-negative bacterial membrane integrity; Gram-positive organisms were generally more tolerant.

Loss of two C. difficile ABC-transporter genes was associated with lower tyrosine/phenylalanine uptake and p-cresol production, without a measurable growth or enterotoxin effect.

Higher predose urinary p-cresol sulfate was associated with a lower postdose acetaminophen sulfate-to-glucuronide ratio.

A phenylalanine/tyrosine-free amino-acid injection mixture reduced tyrosine in rat prefrontal cortex and nucleus accumbens.

Combined phenylalanine/tyrosine depletion decreased dopamine-transient frequency without decreasing transient amplitude in freely moving rats.

In 19 volunteers, tyrosine-containing food bars improved selected working-memory measures during repeated cold-water immersion relative to cold/placebo.

In 17 older adults, 100, 150 and 200 mg/kg oral tyrosine produced dose-dependent plasma increases, larger than young-adult responses at the shared dose.

Load-dependent working-memory performance declined at higher tyrosine doses, particularly in older adults with larger plasma responses.

In a randomized double-blind trial of 70 healthy volunteers, 2 g tyrosine worsened cognitive flexibility under the high-load condition.

An infant treated for tyrosinemia type I developed growth failure, anorexia, lethargy and hypotonia with low phenylalanine and tyrosine during restriction; adding both amino acids reversed these manifestations without reversing cirrhosis.

PAH catalyzes phenylalanine hydroxylation to tyrosine using BH4, molecular oxygen and non-heme ferrous iron.

Human tyrosine hydroxylase catalyzes BH4-dependent tyrosine hydroxylation to L-DOPA, a downstream step in dopamine biosynthesis.

Human LAT1 coexpressed with human SLC3A2/4F2hc in Xenopus oocytes transported large neutral amino acids; extracellular substrates exchanged intracellular leucine and glutamine.

Human TAT1 expressed in Xenopus oocytes transported tryptophan, tyrosine, phenylalanine and L-DOPA independently of sodium.

Reconstituted human LAT1 supported histidine antiport, including exchange with internal cysteine, tyrosine or glutamine; external histidine affinity exceeded internal affinity.

In ten PKU patients, 300 mg/kg/day tyrosine transiently raised calculated brain tyrosine influx from 27% to 90% of normal, but it remained below 70% for half the sampled period.

DNAJC12 interacted with aromatic amino-acid hydroxylases, including PAH, tyrosine hydroxylase and tryptophan hydroxylases.

Expressed human DDC decarboxylated L-DOPA; added PLP enhanced the measured activity.

Human apoDDC has exposed active sites; PLP-titrated structures and kinetics support a cofactor-linked conformational transition.

Human DBH is the copper-enzyme step converting dopamine to norepinephrine; the study resolved its catalytic-core architecture.

Tyrosinase copper loading was transient and inefficient in the Golgi; ATP7A supplied copper for reloading in melanosomes.

Human IYD crystal structures show one bound FMN per polypeptide, with iodotyrosine contacting its isoalloxazine ring in the substrate complex.

Purified soluble human IYD released radiolabeled iodide from diiodotyrosine during reductive enzyme assays.

The IYD variants identified in four affected patients showed markedly reduced iodotyrosine-deiodinase activity in vitro.

HPDL produced 4-hydroxymandelate in human cells.

Isotope tracing identified 4-hydroxymandelate as a CoQ10 head-group biosynthetic intermediate.

A homozygous COQ2 variant caused severe impairment of CoQ10 synthesis in patient fibroblasts.

Resveratrol occupied the tyrosine active site in human TyrRS co-crystals and inhibited amino-acid activation with reported Ki 22 micromolar.

In the resveratrol study, human TyrRS stimulated NAD-dependent PARP1 auto-poly-ADP-ribosylation in biochemical experiments.

The human COMT structure 3BWM includes bound magnesium alongside SAM and the catechol analog.

In CHO cells expressing human TPO, inhibition of heme biosynthesis by succinylacetone decreased surface TPO expression by approximately 80%.

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

Human AOC1 has one copper ion and a tyrosine-derived topaquinone in each of its two active sites.

Human RRM2 radical-center tyrosine mutations abolished the detectable stable radical and ribonucleotide-reductase activity in the tested assays.

Availability and dependencies

The sources