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Tryptophan - 5-HTP - Serotonin - N-acetylserotonin - Melatonin

Tryptophan, an essential amino acid obtained from the diet, undergoes a series of enzymatic reactions to form 5-HTP (5-hydroxytryptophan), serotonin (5-HT), N-acetylserotonin, and melatonin. Each step involves specific enzymes and cofactors crucial for the conversion process.

5-HTP: Tryptophan is initially converted to 5-HTP by the enzyme tryptophan hydroxylase (TPH) with the help of its cofactors, tetrahydrobiopterin (BH4), and iron. BH4 is synthesized using vitamin C (for recyling BH2) and folate, making these vitamins essential for the proper function of TPH. Iron is also a critical cofactor in this step.
5-HT (serotonin): Subsequently, 5-HTP is converted to serotonin (5-HT) by the enzyme 5-HTP decarboxylase. This enzyme requires vitamin B6 as a cofactor for its function. Serotonin functions by binding to specific receptors. Magnesium and zinc serve as cofactors for these serotonin receptors, modulating their activity.
N-Acetylserotonin: Serotonin is converted into N-acetylserotonin by the enzyme serotonin N-acetyltransferase (SNAT). This conversion involves magnesium as a cofactor and requires acetyl-CoA.
Melatonin: N-acetylserotonin is further converted into melatonin by the enzyme Hydroxyindole-O-Methyltransferase (HIOMT) which transfers a methyl group from S-adenosyl methionine to the 5-hydroxy group of N-acetylserotonin.
Some interesting hormonal dependencies:
Estradiol and Tryptophan Hydroxylase: 17β-estradiol (E2) increases the expression of the brain-specific, rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase-2.
Noradrenaline and Melatonin Production: Noradrenaline regulates the activation of aralkylamine N-acetyltransferase that converts 5-hydroxytryptamine (5-HT, serotonin) to N-acetylserotonin

concept

Acetyl-CoA

Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism.[2] Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for energy production.

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Added on Apr 7, 2022 by Barbara Van De Keer
Edited on Jul 1, 2022 by No update