L-Tyrosine

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

evidence_access

Primary abstract

experimental_model

Human tracer feeding study with phenylalanine intakes 7.2–40 mg/kg/day and excess tyrosine.

limitations

This conditional estimate is not a universal intake target or evidence that tyrosine replaces phenylalanine in proteins.

nutrient_topic

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

plain_language

Supplying tyrosine changes how much phenylalanine must be reserved for making it.

primary_references

The Phenylalanine Requirement of Elderly Men and Women Measured by Direct 13C Carbon Oxidation Method Is Similar to That of Young Adults. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31271193/ · DOI 10.1093/jn/nxz137

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 262–268

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human tracer feeding study with phenylalanine intakes 7.2–40 mg/kg/day and excess tyrosine. · source_derived_draft · unverified_draft

## l-phenylalanine-tyrosine-sparing Supplying tyrosine changes how much phenylalanine must be reserved for making it. With excess tyrosine supplied, indicator-amino-acid oxidation in twelve older adults across 66 studies estimated mean phenylalanine requirement at 9.03 mg/kg/day and its upper 95% confidence limit at 15.9 mg/kg/day. Model: Human tracer feeding study with phenylalanine intakes 7.2–40 mg/kg/day and excess tyrosine. Limitations: This conditional estimate is not a universal intake target or evidence that tyrosine replaces phenylalanine in proteins. Evidence access: Primary abstract The Phenylalanine Requirement of Elderly Men and Women Measured by Direct 13C Carbon Oxidation Method Is Similar to That of Young Adults. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31271193/ · DOI 10.1093/jn/nxz137

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

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

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

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

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

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

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

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

evidence_span

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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

dose

Seven days of simple, enteric-coated or placebo preparation

duration

7 days

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Nineteen overweight or obese men in a randomized three-way crossover trial

limitations

This is a mixture and formulation result, not an isolated-capsaicin estimate; the simple-versus-enteric comparison was P=0.09.

nutrient_topic

Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin

organism

Nineteen overweight or obese men in a randomized three-way crossover trial

plain_language

A non-enteric capsaicin/green-tea/caffeine/tyrosine/calcium mixture increased 24-hour energy expenditure by 160 kJ/day versus placebo; the enteric version did not.

primary_references

Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15870822/ DOI: 10.1038/sj.ejcn.1602121

route

Oral multi-ingredient supplement

tissue

Respiration-chamber energy expenditure

Capsaicin: mechanism of action and interactions (2026-09-20) · lines 132–141

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Nineteen overweight or obese men in a randomized three-way crossover trial · source_derived_draft · unverified_draft

## capsaicin-multi-ingredient-energy A non-enteric capsaicin/green-tea/caffeine/tyrosine/calcium mixture increased 24-hour energy expenditure by 160 kJ/day versus placebo; the enteric version did not. Model/species: Nineteen overweight or obese men in a randomized three-way crossover trial Tissue/system: Respiration-chamber energy expenditure Exposure: Seven days of simple, enteric-coated or placebo preparation Route: Oral multi-ingredient supplement Duration: 7 days Limits: This is a mixture and formulation result, not an isolated-capsaicin estimate; the simple-versus-enteric comparison was P=0.09. Primary reference: Bioactive food stimulants of sympathetic activity: effect on 24-h energy expenditure and fat oxidation. (2005). https://pubmed.ncbi.nlm.nih.gov/15870822/ DOI: 10.1038/sj.ejcn.1602121 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

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

evidence_access

Primary abstract

experimental_model

In-vitro human cytosolic and mitochondrial synthetase assays.

limitations

Assay mischarging does not establish clinical proteotoxicity from a usual phenylalanine intake.

nutrient_topic

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

plain_language

Similar-looking molecules can challenge protein-building accuracy.

primary_references

Bacterial and eukaryotic phenylalanyl-tRNA synthetases catalyze misaminoacylation of tRNA(Phe) with 3,4-dihydroxy-L-phenylalanine. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22035791/ · DOI 10.1016/j.chembiol.2011.08.008

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 134–140

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In-vitro human cytosolic and mitochondrial synthetase assays. · source_derived_draft · unverified_draft

## l-phenylalanine-charging-fidelity Similar-looking molecules can challenge protein-building accuracy. Human cytosolic and mitochondrial phenylalanyl-tRNA synthetases could mischarge L-DOPA in biochemical assays; cytosolic editing hydrolyzed L-DOPA- and tyrosine-mischarged tRNA, whereas the mitochondrial system discriminated less effectively. Model: In-vitro human cytosolic and mitochondrial synthetase assays. Limitations: Assay mischarging does not establish clinical proteotoxicity from a usual phenylalanine intake. Evidence access: Primary abstract Bacterial and eukaryotic phenylalanyl-tRNA synthetases catalyze misaminoacylation of tRNA(Phe) with 3,4-dihydroxy-L-phenylalanine. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22035791/ · DOI 10.1016/j.chembiol.2011.08.008

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

evidence_access

Primary abstract

experimental_model

Four two-week crossover phases involving LNAA/placebo with or without medical product.

limitations

Small, short study; not a replacement recommendation for established PKU management.

nutrient_topic

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

plain_language

A mixture can change outcomes, but the existing diet affects its added value.

primary_references

The effects of large neutral amino acid supplements in PKU: an MRS and neuropsychological study. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17368065/ · DOI 10.1016/j.ymgme.2007.02.002

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 206–212

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four two-week crossover phases involving LNAA/placebo with or without medical product. · source_derived_draft · unverified_draft

## l-phenylalanine-lnaa-clinical-boundary A mixture can change outcomes, but the existing diet affects its added value. In a 16-person PKU crossover study, LNAA supplementation produced limited executive-function benefits and lowered plasma phenylalanine mainly when participants were not taking their usual medical product. Model: Four two-week crossover phases involving LNAA/placebo with or without medical product. Limitations: Small, short study; not a replacement recommendation for established PKU management. Evidence access: Primary abstract The effects of large neutral amino acid supplements in PKU: an MRS and neuropsychological study. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17368065/ · DOI 10.1016/j.ymgme.2007.02.002

evidence_access

Primary full text

experimental_model

Three three-week crossover periods; serum/urine melatonin, urinary dopamine and plasma amino-acid ratios.

limitations

Urinary dopamine and melatonin are surrogate readouts, not a direct demonstration of restored brain neurotransmitter concentrations.

nutrient_topic

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

plain_language

A downstream marker can improve even when phenylalanine concentration stays similar.

primary_references

Large neutral amino acid supplementation increases melatonin synthesis in phenylketonuria: a new biomarker. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23164313/ · DOI 10.1016/j.jpeds.2012.10.015

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 214–220

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Three three-week crossover periods; serum/urine melatonin, urinary dopamine and plasma amino-acid ratios. · source_derived_draft · unverified_draft

## l-phenylalanine-lnaa-monoamine-markers A downstream marker can improve even when phenylalanine concentration stays similar. In ten adults with PKU, LNAA supplementation increased melatonin measures and urinary dopamine while phenylalanine itself did not significantly change. Model: Three three-week crossover periods; serum/urine melatonin, urinary dopamine and plasma amino-acid ratios. Limitations: Urinary dopamine and melatonin are surrogate readouts, not a direct demonstration of restored brain neurotransmitter concentrations. Evidence access: Primary full text Large neutral amino acid supplementation increases melatonin synthesis in phenylketonuria: a new biomarker. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23164313/ · DOI 10.1016/j.jpeds.2012.10.015

evidence_access

Primary abstract

experimental_model

Human indicator amino-acid oxidation/balance feeding study without dietary tyrosine.

limitations

Population and protocol differ from the older-adult excess-tyrosine study; different estimates are not treated as a scientific contradiction.

nutrient_topic

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

plain_language

When tyrosine is absent, phenylalanine must cover an additional metabolic demand.

primary_references

The daily phenylalanine requirement of healthy Indian adults. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16762944/ · DOI 10.1093/ajcn/83.6.1331

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 270–276

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human indicator amino-acid oxidation/balance feeding study without dietary tyrosine. · source_derived_draft · unverified_draft

## l-phenylalanine-no-tyrosine-requirement When tyrosine is absent, phenylalanine must cover an additional metabolic demand. A tracer study in healthy Indian adults consuming no tyrosine estimated mean phenylalanine requirement at about 38 mg/kg/day. Model: Human indicator amino-acid oxidation/balance feeding study without dietary tyrosine. Limitations: Population and protocol differ from the older-adult excess-tyrosine study; different estimates are not treated as a scientific contradiction. Evidence access: Primary abstract The daily phenylalanine requirement of healthy Indian adults. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16762944/ · DOI 10.1093/ajcn/83.6.1331

evidence_access

Primary abstract

experimental_model

Enzyme mechanism described in the primary PRISM clinical report.

limitations

Lowering phenylalanine through this bypass does not restore the PAH-to-tyrosine reaction.

nutrient_topic

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

plain_language

A drug can remove the accumulating substrate through a different chemical route.

primary_references

Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM). · 2018 · https://pubmed.ncbi.nlm.nih.gov/29653686/ · DOI 10.1016/j.ymgme.2018.03.006

L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 238–244

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Enzyme mechanism described in the primary PRISM clinical report. · source_derived_draft · unverified_draft

## l-phenylalanine-pal-bypass A drug can remove the accumulating substrate through a different chemical route. Pegvaliase supplies a PEGylated microbial phenylalanine ammonia lyase pathway that converts phenylalanine to trans-cinnamate and ammonia rather than tyrosine. Model: Enzyme mechanism described in the primary PRISM clinical report. Limitations: Lowering phenylalanine through this bypass does not restore the PAH-to-tyrosine reaction. Evidence access: Primary abstract Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM). · 2018 · https://pubmed.ncbi.nlm.nih.gov/29653686/ · DOI 10.1016/j.ymgme.2018.03.006

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

evidence_access

Primary abstract

experimental_model

Overnight-fasted rats receiving defined meals with different amino-acid mixtures.

limitations

Not a validated universal human threshold or proof that protein-rich meals worsen mood.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

A higher blood level need not mean more tryptophan reaches the brain.

primary_references

Acute reduction of brain serotonin and 5-HIAA following food consumption: correlation with the ratio of serum tryptophan to the sum of competing amino acids. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1080186/ · DOI 10.1007/BF01256759

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 58–64

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Overnight-fasted rats receiving defined meals with different amino-acid mixtures. · source_derived_draft · unverified_draft

## tryptophan-brain-competition A higher blood level need not mean more tryptophan reaches the brain. In rat meal experiments, brain tryptophan and 5-hydroxyindoles tracked the serum tryptophan-to-competing-neutral-amino-acid ratio better than serum tryptophan alone. Model: Overnight-fasted rats receiving defined meals with different amino-acid mixtures. Limitations: Not a validated universal human threshold or proof that protein-rich meals worsen mood. Evidence access: Primary abstract Acute reduction of brain serotonin and 5-HIAA following food consumption: correlation with the ratio of serum tryptophan to the sum of competing amino acids. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1080186/ · DOI 10.1007/BF01256759

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text, Figures 1–3

experimental_model

C. sporogenes ClosTron mutant and LC–MS/MS.

limitations

The mutation affects phenylalanine and tyrosine products as well; effects cannot all be assigned to indolepropionate.

nutrient_topic

Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan

plain_language

A missing microbial enzyme stopped production despite available tryptophan.

primary_references

A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29168502/ · DOI 10.1038/nature24661

trigger_kind

machinery_impairment Imported condition classification; unverified.

Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 490–496

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · C. sporogenes ClosTron mutant and LC–MS/MS. · source_derived_draft · unverified_draft

## tryptophan-fldc-loss A missing microbial enzyme stopped production despite available tryptophan. Disrupting fldC in C. sporogenes abolished indolepropionate accumulation in culture and altered aromatic-amino-acid metabolism. Model: C. sporogenes ClosTron mutant and LC–MS/MS. Limitations: The mutation affects phenylalanine and tyrosine products as well; effects cannot all be assigned to indolepropionate. Evidence access: Primary full text, Figures 1–3 A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29168502/ · DOI 10.1038/nature24661

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

evidence_span

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experimental_model

Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom

exposure

Bound 7,8-dihydrobiopterin and iron

limitations

Structural chemistry of the rate-limiting step. It is a rat enzyme structure with a cofactor analogue, not a measurement of iron status in an animal.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Rat enzyme

plain_language

The first and slowest step of making noradrenaline needs an iron atom and a molecule of oxygen.

primary_references

[cold-p9753429] Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. (1998). https://pubmed.ncbi.nlm.nih.gov/9753429/ DOI: 10.1021/bi981462g

tissue_or_cell_type

Purified catalytic and tetramerization domains

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 533–544

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom · source_derived_draft · unverified_draft

### cold-th-iron-oxygen-pterin Tyrosine hydroxylase is a non-heme iron enzyme that uses molecular oxygen to hydroxylate tyrosine to L-DOPA and tetrahydrobiopterin to 4a-hydroxybiopterin in the rate-limiting step of the catecholamine biosynthetic pathway. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The first and slowest step of making noradrenaline needs an iron atom and a molecule of oxygen. organism: Rat enzyme tissue_or_cell_type: Purified catalytic and tetramerization domains experimental_model: Crystal structure of rat tyrosine hydroxylase with a cofactor analogue and iron at 2.3 angstrom limitations: Structural chemistry of the rate-limiting step. It is a rat enzyme structure with a cofactor analogue, not a measurement of iron status in an animal. exposure: Bound 7,8-dihydrobiopterin and iron evidence_span: {"source_cache": "artifacts/cold-research/9753429.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9", "start_char": 0, "end_char": 1695, "text_sha256": "3c76ec6d5dadb463c0a044175d5a78fbd02df4da7c339029c8c232e8878175b9"} [cold-p9753429] Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site. (1998). https://pubmed.ncbi.nlm.nih.gov/9753429/ DOI: 10.1021/bi981462g

availability_state

biomarker_context Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Same ten-person 3 g comparison.

limitations

The ratio is not a measured change in brain serotonin or dopamine.

nutrient_topic

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

plain_language

Transport competition depends partly on the mixture reaching blood.

primary_references

Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

trigger_kind

biomarker_context Imported condition classification; unverified.

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 90–96

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same ten-person 3 g comparison. · source_derived_draft · unverified_draft

## aspartame-formulation-ratio Transport competition depends partly on the mixture reaching blood. Solution versus capsules produced a higher plasma phenylalanine-to-other-LNAA ratio, 0.36 versus 0.23. Model: Same ten-person 3 g comparison. Limitations: The ratio is not a measured change in brain serotonin or dopamine. Evidence access: Primary abstract Plasma amino acid concentrations in normal adults administered aspartame in capsules or solution: lack of bioequivalence. · 1987 · https://pubmed.ncbi.nlm.nih.gov/3574137/ · DOI 10.1016/0026-0495(87)90052-7

evidence_access

Primary full text and author-list correction

experimental_model

Same human crossover.

limitations

Not comparable to isolated cells or susceptible-mouse feeding by dose or endpoint. Correction record: Publisher correction concerns author order, affiliations and citation; no experimental-result correction is stated. Correction PMID 25951455 inspected in full text. https://doi.org/10.1371/journal.pone.0126039

nutrient_topic

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

plain_language

Receptor activity did not translate into a distinct measured response in this meal.

primary_references

Aspartame sensitivity? A double blind randomised crossover study. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25786106/ · DOI 10.1371/journal.pone.0116212

Aspartame: digestion, taste, metabolite dependencies and experimental signaling (2026-09-20) · lines 330–336

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same human crossover. · source_derived_draft · unverified_draft

## aspartame-snackbar-hormones Receptor activity did not translate into a distinct measured response in this meal. GLP-1, GIP, tyrosine and phenylalanine responses were similar with aspartame and control snack bars. Model: Same human crossover. Limitations: Not comparable to isolated cells or susceptible-mouse feeding by dose or endpoint. Correction record: Publisher correction concerns author order, affiliations and citation; no experimental-result correction is stated. Correction PMID 25951455 inspected in full text. https://doi.org/10.1371/journal.pone.0126039 Evidence access: Primary full text and author-list correction Aspartame sensitivity? A double blind randomised crossover study. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25786106/ · DOI 10.1371/journal.pone.0116212