Component

Human tryptophan hydroxylase 1 / TPH1

Human tryptophan hydroxylase 1 / TPH1. Species, exposure and limitations are retained in each linked claim.

3 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. Purified human pineal TPH catalyzed tryptophan hydroxylation to 5-hydroxytryptophan.

    Human tryptophan hydroxylase 1 / TPH1 → 5-Hydroxy-L-tryptophan source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"}
    experimental_model
    Recombinant enzyme purification and catalysis
    exposure
    L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme
    limitations
    TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person.
    nutrient_topic
    Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
    organism
    Human pineal TPH1 expressed in E. coli
    plain_language
    The amino acid tryptophan must pass through an enzyme-controlled first step.
    primary_references
    [melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
    tissue_or_cell_type
    Tryptophan hydroxylation

    Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 136–147

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

    ### melatonin-tph1-hydroxylation Purified human pineal TPH catalyzed tryptophan hydroxylation to 5-hydroxytryptophan. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The amino acid tryptophan must pass through an enzyme-controlled first step. organism: Human pineal TPH1 expressed in E. coli tissue_or_cell_type: Tryptophan hydroxylation experimental_model: Recombinant enzyme purification and catalysis limitations: TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person. exposure: L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme evidence_span: {"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"} [melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
    Complete structured claim and evidence

  2. The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron.

    Human tryptophan hydroxylase 1 / TPH1 → Ferrous iron source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/melatonin-research/11747434.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06", "start_char": 0, "end_char": 2063, "text_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06"}
    experimental_model
    NMR substrate/cofactor geometry and enzyme modeling
    exposure
    L-tryptophan and bound BH2 cofactor analogue
    limitations
    BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured.
    nutrient_topic
    Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
    organism
    Recombinant human TPH1 catalytic domain
    plain_language
    The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin.
    primary_references
    [melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x
    tissue_or_cell_type
    Non-heme iron active site

    Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 162–173

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NMR substrate/cofactor geometry and enzyme modeling · source_derived_draft · unverified_draft

    ### melatonin-tph1-iron The human TPH catalytic domain positioned tryptophan and a pterin analogue near its catalytic non-heme iron. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The upstream hydroxylation machinery contains iron; giving more iron is not automatically a way to make more melatonin. organism: Recombinant human TPH1 catalytic domain tissue_or_cell_type: Non-heme iron active site experimental_model: NMR substrate/cofactor geometry and enzyme modeling limitations: BH2 was a structural analogue in this experiment, not a demonstration that BH2 replaces physiological BH4. No clinical iron-deficiency threshold measured. exposure: L-tryptophan and bound BH2 cofactor analogue evidence_span: {"source_cache": "artifacts/melatonin-research/11747434.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06", "start_char": 0, "end_char": 2063, "text_sha256": "c98a1e028f9c3d7f749d37794a8e976c8c808e0ca9c5f08c394d9d29ae639e06"} [melatonin-p11747434] Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity. (2001). https://pubmed.ncbi.nlm.nih.gov/11747434/ DOI: 10.1021/bi015722x
    Complete structured claim and evidence

What acts on it

  1. Human pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected.

    Tetrahydrobiopterin / BH4 → Human tryptophan hydroxylase 1 / TPH1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"}
    experimental_model
    Recombinant enzyme purification and catalysis
    exposure
    L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme
    limitations
    TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person.
    nutrient_topic
    Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin
    organism
    Human pineal TPH1 expressed in E. coli
    plain_language
    The pterin cofactor participates chemically; it is not interchangeable with folate.
    primary_references
    [melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
    tissue_or_cell_type
    Tryptophan hydroxylation

    Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 149–160

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

    ### melatonin-tph1-bh4 Human pineal TPH activity was measured with BH4, and a transient 4alpha-hydroxytetrahydrobiopterin intermediate was detected. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pterin cofactor participates chemically; it is not interchangeable with folate. organism: Human pineal TPH1 expressed in E. coli tissue_or_cell_type: Tryptophan hydroxylation experimental_model: Recombinant enzyme purification and catalysis limitations: TPH1 and neuronal TPH2 are distinct. A cofactor-dependent reaction does not prove supplemental cofactor increases melatonin in a replete person. exposure: L-tryptophan with tetrahydrobiopterin; purified tetrameric enzyme evidence_span: {"source_cache": "artifacts/melatonin-research/10525150.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f", "start_char": 0, "end_char": 1489, "text_sha256": "032acfb7b1818f5282f5457e093a7e371895bbdc95f058c8958766fc57f9118f"} [melatonin-p10525150] Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. (1999). https://pubmed.ncbi.nlm.nih.gov/10525150/ DOI: 10.1016/s0167-4838(99)00184-3
    Complete structured claim and evidence

In the sources

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

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards