Component

Human tyrosine hydroxylase

Human catecholamine-biosynthetic enzyme measured in SH-SY5Y cells; distinct from DBH.

10 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

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

    Human tyrosine hydroxylase → L-3,4-Dihydroxyphenylalanine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human TH variant study; established enzyme reaction described in the abstract.
    limitations
    This is a downstream connection, not evidence that oral phenylalanine predictably raises brain dopamine.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    Producing tyrosine is only the first part of the route toward dopamine.
    primary_references
    Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38084654/ · DOI 10.1002/jimd.12690

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 118–124

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TH variant study; established enzyme reaction described in the abstract. · source_derived_draft · unverified_draft

    ## l-phenylalanine-tyrosine-next-step Producing tyrosine is only the first part of the route toward dopamine. Human tyrosine hydroxylase catalyzes BH4-dependent tyrosine hydroxylation to L-DOPA, a downstream step in dopamine biosynthesis. Model: Human TH variant study; established enzyme reaction described in the abstract. Limitations: This is a downstream connection, not evidence that oral phenylalanine predictably raises brain dopamine. Evidence access: Primary abstract Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38084654/ · DOI 10.1002/jimd.12690
    Complete structured claim and evidence

What acts on it

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

    Tetrahydrobiopterin / BH4 → Human tyrosine hydroxylase source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation.
    limitations
    These kinetic values are not blood targets or instructions to supplement BH4.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    The cofactor response changes with enzyme regulation.
    primary_references
    Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10411647/ · DOI 10.1046/j.1432-1327.1999.00445.x

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 28–34

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation. · source_derived_draft · unverified_draft

    ## l-tyrosine-th-cofactor-regulation The cofactor response changes with enzyme regulation. Recombinant human TH1 bound natural BH4 with negative cooperativity; Ser40 phosphorylation increased apparent BH4 affinity. Model: Human TH1 kinetics and surface plasmon resonance; PKA phosphorylation. Limitations: These kinetic values are not blood targets or instructions to supplement BH4. Evidence access: Primary abstract Tyrosine hydroxylase binds tetrahydrobiopterin cofactor with negative cooperativity, as shown by kinetic analyses and surface plasmon resonance detection. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10411647/ · DOI 10.1046/j.1432-1327.1999.00445.x
    Complete structured claim and evidence

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

    Iron → Human tyrosine hydroxylase source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy.
    limitations
    A hydration-dependent structural change is not evidence that ordinary dehydration causes dopamine deficiency.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    Iron participates in the enzyme itself, and its local environment matters.
    primary_references
    Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10499095/ · DOI 10.1007/s007750050308

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 36–42

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy. · source_derived_draft · unverified_draft

    ## l-tyrosine-th-iron Iron participates in the enzyme itself, and its local environment matters. Reconstituted human TH1 contained high-spin Fe(II); dehydration changed iron coordination and rehydration reversed the spectroscopic change. Model: Purified full-length and truncated human TH1; Mossbauer and X-ray absorption spectroscopy. Limitations: A hydration-dependent structural change is not evidence that ordinary dehydration causes dopamine deficiency. Evidence access: Primary abstract Iron coordination geometry in full-length, truncated, and dehydrated forms of human tyrosine hydroxylase studied by Mössbauer and X-ray absorption spectroscopy. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10499095/ · DOI 10.1007/s007750050308
    Complete structured claim and evidence

  3. 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.

    Iron → Human tyrosine hydroxylase source_derived_draftungraded
    Experimental context and source evidence
    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"}
    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
    Complete structured claim and evidence

  4. The pterin binds in the active-site cleft forming an aromatic stacking interaction with Phe300, which is itself hydroxylated in the meta position by an autocatalytic process and anchored by a hydrogen bond to the carbonyl of Gln310; the iron sits 5.6 angstrom from the pterin 4a carbon, and molecular oxygen could bind in a bridging position between the pterin and the iron before substrate hydroxylation.

    Tetrahydrobiopterin / BH4 → Human tyrosine hydroxylase source_derived_draftungraded
    Experimental context and source evidence
    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"}
    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 oxygen molecule slots into the gap between the cofactor and the iron.
    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 546–557

    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-pterin-geometry The pterin binds in the active-site cleft forming an aromatic stacking interaction with Phe300, which is itself hydroxylated in the meta position by an autocatalytic process and anchored by a hydrogen bond to the carbonyl of Gln310; the iron sits 5.6 angstrom from the pterin 4a carbon, and molecular oxygen could bind in a bridging position between the pterin and the iron before substrate hydroxylation. 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 oxygen molecule slots into the gap between the cofactor and the iron. 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
    Complete structured claim and evidence

  5. In pooled SH-SY5Y immunoblots after 24 hours, TH protein rose to a maximum around 170% of control; statistical significance in Results/Fig.4 was reached at 1000 micromolar loading ascorbate (approximately 1.6–2.5 mM intracellular).

    L-Ascorbate → Human tyrosine hydroxylase source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing.
    experimental_model
    Human SH-SY5Y neuroblastoma cultures
    exposure
    24-hour cell culture; 1000 micromolar medium loading reaches significance in pooled Fig.4B; intracellular approximately 1.6–2.5 mM.
    limitations
    Results/Fig.4 exposure is retained because Discussion describes significant effects at lower loading concentrations. No universal neuronal vitamin C threshold established.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Homo sapiens
    plain_language
    At the tested higher exposure, vitamin C increased the amount of an enzyme upstream of dopamine synthesis.
    primary_references
    [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054
    tissue_or_cell_type
    Neuronal tumor cell line

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 833–844

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SH-SY5Y neuroblastoma cultures · source_derived_draft · unverified_draft

    ### vc-enzyme-neuronal-th-protein In pooled SH-SY5Y immunoblots after 24 hours, TH protein rose to a maximum around 170% of control; statistical significance in Results/Fig.4 was reached at 1000 micromolar loading ascorbate (approximately 1.6–2.5 mM intracellular). Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: At the tested higher exposure, vitamin C increased the amount of an enzyme upstream of dopamine synthesis. organism: Homo sapiens tissue_or_cell_type: Neuronal tumor cell line experimental_model: Human SH-SY5Y neuroblastoma cultures limitations: Results/Fig.4 exposure is retained because Discussion describes significant effects at lower loading concentrations. No universal neuronal vitamin C threshold established. cross_nutrient: Vitamin C chemistry in collagen, modified-lysine/carnitine metabolism or copper-dependent peptide/catecholamine processing. exposure: 24-hour cell culture; 1000 micromolar medium loading reaches significance in pooled Fig.4B; intracellular approximately 1.6–2.5 mM. [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054
    Complete structured claim and evidence

Where it participates (unsigned role)

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

    Human chaperone DNAJC12 → Human phenylalanine hydroxylase / PAH source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human DNAJC12 deficiency study with functional interaction experiments.
    limitations
    Interaction does not imply identical effects in all tissues or rescue by extra substrate.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    A shared chaperone supports several amino-acid processing enzymes.
    primary_references
    Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28132689/ · DOI 10.1016/j.ajhg.2017.01.002

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 102–108

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human DNAJC12 deficiency study with functional interaction experiments. · source_derived_draft · unverified_draft

    ## l-phenylalanine-dnaj-chaperone A shared chaperone supports several amino-acid processing enzymes. DNAJC12 interacted with aromatic amino-acid hydroxylases, including PAH, tyrosine hydroxylase and tryptophan hydroxylases. Model: Human DNAJC12 deficiency study with functional interaction experiments. Limitations: Interaction does not imply identical effects in all tissues or rescue by extra substrate. Evidence access: Primary abstract Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28132689/ · DOI 10.1016/j.ajhg.2017.01.002
    Complete structured claim and evidence

  2. Biallelic DNAJC12 variants in six patients from four families accompanied hyperphenylalaninemia and neurotransmitter abnormalities; functional studies found reduced PAH activity.

    Human chaperone DNAJC12 → Human phenylalanine hydroxylase / PAH source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human genetic case series and functional experiments.
    limitations
    Early combined BH4/neurotransmitter-precursor treatment was not a controlled test of phenylalanine supplementation.
    nutrient_topic
    L-Phenylalanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Phenylalanine
    plain_language
    Phenylalanine can accumulate because its supporting machinery is defective.
    primary_references
    Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28132689/ · DOI 10.1016/j.ajhg.2017.01.002
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Phenylalanine: transport, protein synthesis, cofactor recycling and cross-nutrient mechanisms (2026-09-19) · lines 110–116

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human genetic case series and functional experiments. · source_derived_draft · unverified_draft

    ## l-phenylalanine-dnaj-failure Phenylalanine can accumulate because its supporting machinery is defective. Biallelic DNAJC12 variants in six patients from four families accompanied hyperphenylalaninemia and neurotransmitter abnormalities; functional studies found reduced PAH activity. Model: Human genetic case series and functional experiments. Limitations: Early combined BH4/neurotransmitter-precursor treatment was not a controlled test of phenylalanine supplementation. Evidence access: Primary abstract Biallelic Mutations in DNAJC12 Cause Hyperphenylalaninemia, Dystonia, and Intellectual Disability. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28132689/ · DOI 10.1016/j.ajhg.2017.01.002
    Complete structured claim and evidence

  3. Ergothioneine limited ATP loss, protein carbonylation and tyrosine hydroxylase loss in the human 6-OHDA cell experiments.

    L-Ergothioneine → Human dopaminergic-cell ATP content source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human iPSC-derived neurons and neuroblastoma cells.
    limitations
    These correlated outcomes do not identify a single direct mitochondrial target.
    nutrient_topic
    Ergothioneine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Ergothioneine
    plain_language
    Protection involved energy and dopamine-related cell markers.
    primary_references
    Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693

    Ergothioneine: transport, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 392–398

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human iPSC-derived neurons and neuroblastoma cells. · source_derived_draft · unverified_draft

    ## ergothioneine-dopaminergic-atp Protection involved energy and dopamine-related cell markers. Ergothioneine limited ATP loss, protein carbonylation and tyrosine hydroxylase loss in the human 6-OHDA cell experiments. Model: Human iPSC-derived neurons and neuroblastoma cells. Limitations: These correlated outcomes do not identify a single direct mitochondrial target. Evidence access: Primary abstract Ergothioneine-Mediated Neuroprotection of Human iPSC-Derived Dopaminergic Neurons. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38929132/ · DOI 10.3390/antiox13060693
    Complete structured claim and evidence

  4. Sepiapterin increased norepinephrine content in SH-SY5Y cultures and 50 micromolar ascorbate increased the response further after 24 hours.

    Sepiapterin → Norepinephrine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Ascorbate interacts with the pterin cofactor pathway supporting amino-acid-derived catecholamine synthesis; sepiapterin is kept distinct from BH4.
    experimental_model
    Human SH-SY5Y neuroblastoma cultures
    exposure
    Sepiapterin dose series with or without 50 micromolar ascorbate, 24 hours; Fig.3C.
    limitations
    Fig.3C tests sepiapterin, not direct BH4 dosing; BH4 recycling by ascorbate is an interpretation rather than a measured reaction in this experiment.
    nutrient_topic
    Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
    organism
    Homo sapiens
    plain_language
    Supporting a second cofactor pathway enhanced the neuronal response to vitamin C.
    primary_references
    [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054
    tissue_or_cell_type
    Neuronal tumor cell line

    Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 846–857

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SH-SY5Y neuroblastoma cultures · source_derived_draft · unverified_draft

    ### vc-enzyme-sepiapterin-co-response Sepiapterin increased norepinephrine content in SH-SY5Y cultures and 50 micromolar ascorbate increased the response further after 24 hours. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supporting a second cofactor pathway enhanced the neuronal response to vitamin C. organism: Homo sapiens tissue_or_cell_type: Neuronal tumor cell line experimental_model: Human SH-SY5Y neuroblastoma cultures limitations: Fig.3C tests sepiapterin, not direct BH4 dosing; BH4 recycling by ascorbate is an interpretation rather than a measured reaction in this experiment. cross_nutrient: Ascorbate interacts with the pterin cofactor pathway supporting amino-acid-derived catecholamine synthesis; sepiapterin is kept distinct from BH4. exposure: Sepiapterin dose series with or without 50 micromolar ascorbate, 24 hours; Fig.3C. [may2012] Mechanisms of ascorbic acid stimulation of norepinephrine synthesis in neuronal cells. (2012). https://pubmed.ncbi.nlm.nih.gov/22925890/ DOI: 10.1016/j.bbrc.2012.08.054
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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