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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 · from cache · sorted by publication date

  1. 1
    A Functional SNP in the Promoter Region of Ovine IDO2 Associated With Melatonin Levels via Affecting Transcription Activity by CLOCK.

    Jiang X, Chi S, Wang X, Chen M, Tie Z, Yang H, Wang C, Liu G. · 2026-08-01

    unreviewed
  2. 2
    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

    cited 1× open access unreviewed
  3. 3
    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
  4. 4
    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
  5. 5
    Physiological relevance of autocrine melatonin signaling in pineal and extrapineal sites: a systematic review.

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

    cited 8× open access unreviewed
  6. 6
    Seasonal metabolic oscillation: adiposity cycling as a candidate amplifier of mood seasonality in seasonal affective and bipolar disorders.

    Öztürk EÖ, Aydemir Ö. · 2026-08-03

    open access unreviewed
  7. 7
    Targeting the microbiota-gut-brain axis in post-stroke insomnia: a phase-dependent therapeutic framework.

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

    cited 1× open access unreviewed
  8. 8
    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
  9. 9
    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 21× open access unreviewed
  10. 10
    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 10× open access unreviewed

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