Serotonin & Melatonin Synthesis

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.