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PW-045 Amino Acid & Nitrogen Metabolism Anabolic unreviewed

Serotonin & Melatonin Synthesis

L-Tryptophan Serotonin -> melatonin
Compartment
Cytosol
Main tissue
Enterochromaffin cells, CNS raphe nuclei, pineal
Rate-limiting
Tryptophan hydroxylase (TPH1/2)
Steps
3

Reaction steps

In source order, 3 total

showing 1–3
  1. 1

    L-Tryptophan + O2 + BH4 -> 5-hydroxytryptophan

    Tryptophan hydroxylase (TPH1/2) 1.14.16.4 ST-0346 Irreversible rate-limiting BH4 O2 Fe2+
    In Tryptophan O2 BH4
    Out 5-Hydroxytryptophan
    › Notes

    Rate-limiting step.

  2. 2

    5-Hydroxytryptophan -> serotonin (5-HT) + CO2

    Aromatic L-amino acid decarboxylase (DDC) 4.1.1.28 ST-0347 Irreversible/directional PLP (B6)
    In 5-Hydroxytryptophan
    Out Serotonin (5-HT) CO2
    › Notes

    Serotonin is degraded by MAO to 5-HIAA, the urinary marker of carcinoid syndrome.

  3. 3

    Serotonin + acetyl-CoA -> N-acetylserotonin; then + SAM -> melatonin

    Serotonin N-acetyltransferase (AANAT) + ASMT/HIOMT 2.3.1.87 / 2.1.1.4 ST-0348 Irreversible/directional Acetyl-CoA SAM
    In Serotonin Acetyl-CoA
    Out N-Acetylserotonin Then S-adenosylmethionine (SAM)
    › Notes

    Pineal, night-time. AANAT is the rate-controlling, light-suppressed step.

Showing all 3 steps.

Recent literature

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Europe PMC · fetched just now · sorted by publication date

  1. 1
    Hierarchical Disruption of the Tryptophan-Melatonin Axis Contributes to Glioma Progression Through AKT/ERK/STAT3 Signalling.

    Tan B, Yao S, He S, Chen T, Chen H, Yang W, Tang X, Xu T, Zhang J, Yin X, Chen Y, Song P. · 2026-06-01

    open access unreviewed
  2. 2
    Melatonin ameliorates autistic-like behaviors by restoring gut microbiota-derived tryptophan metabolites.

    Shen J, Gao J, Gao L, Yan D, Wang Y, Meng J, Li H, Chen D, Wu J. · 2026-03-05

    open access unreviewed
  3. 3
    Metformin and Sitagliptin Impact the Brain Kynurenine Pathway: Region-Specific Modulation of Neuroactive Metabolites in Non-Diabetic Male Rats.

    Bednarz K, Kloc R, Słowik T, Urbanska EM. · 2026-02-19

    open access unreviewed
  4. 4
    Physiological relevance of autocrine melatonin signaling in pineal and extrapineal sites: a systematic review.

    Ndinganire G, Ntamukunzi G, Alagbonsi AI. · 2026-01-19

    cited 2× open access unreviewed
  5. 5
    Targeting the microbiota-gut-brain axis in post-stroke insomnia: a phase-dependent therapeutic framework.

    Zhou Y, Huang Y, Bi X. · 2026-04-09

    open access unreviewed
  6. 6
    Eggs as a Nutrient-Rich Food with Potential Relevance to Sleep Metabolic Health, and Well-Being During the Menopausal Transition: A Narrative Review.

    Convit L, Nicola CM, Urwin CS, Roberts SSH, Tan SY, Hoffmann SM, Condo D, Daly RM, Hamilton DL, Snipe RMJ. · 2025-12-08

    open access unreviewed
  7. 7
    The human gut microbiota is associated with host lifestyle: a comprehensive narrative review.

    Zeng Q, Feng X, Hu Y, Su S. · 2025-06-23

    cited 6× open access unreviewed
  8. 8
    High-fat diet-negative impact on female fertility: from mechanisms to protective actions of antioxidant matrices.

    Di Berardino C, Barceviciute U, Camerano Spelta Rapini C, Peserico A, Capacchietti G, Bernabò N, Russo V, Gat… · 2024-06-10

    cited 8× open access unreviewed
  9. 9
    Mapping and Screening of Candidate Gene Regulating the Biomass Yield of Sorghum (<i>Sorghum bicolor</i> L.).

    Li M, Cai Q, Liang Y, Zhao Y, Hao Y, Qin Y, Qiao X, Han Y, Li H. · 2024-01-08

    open access unreviewed
  10. 10
    Food Intake and Sleep Disorders in Children and Adolescents with Obesity.

    Calcaterra V, Rossi V, Tagi VM, Baldassarre P, Grazi R, Taranto S, Zuccotti G. · 2023-11-09

    cited 28× open access unreviewed

External claims. These come from an index outside this database and are not checked against it. Treat them as leads.