MELATONIN synthesis pathway in the body

Pineal and retinal SEROTONIN (5-HT) synthesis is up-regulated at night controlled by ß-adrenergic signaling.   Sympathetic nerves from the superior cervical ganglion (SCG) innervate the pineal gland via NOREPINEPHRINE (NE)-stimulation of adenergic receptors (ARs). Increased SEROTONIN synthesis is due to increased protein expression of tryptophan hydroxylase (TPH), the rate-limiting enzyme of SEROTONIN synthesis.

Diurnal variation in MELATONIN synthesis is brought about by NOREPINEPHRINE (NE).   Secreted by the postganglionic sympathetic nerves (the superior cervical ganglion/SCG) that innervate the pineal gland. NE interacts with ß1-adrenoreceptors on the surface of the pinealocytes (pineal cells) to increase pineal cAMP, which in turn activate the N-acetyltransferase (NAT) required for MELATONIN synthesis in the biosynthesis pathway, converting tryptophan to MELATONIN.

** The body often uses Tryptophan to make vitamin B3, at a very high cost of 60mg L-Tryptophan to make just 1 mg B3.

SAMe (a methyl donor molecule made from the amino acid methionine and ATP) is essential for MELATONIN and SEROTONIN production

-   SAMe is the daytime equivalent of MELATONIN - and like MELATONIN, it is produced under control of the master biological clock;

-   Natural synthesis of MELATONIN (and SEROTONIN) depends on adequate SAMe synthesis during the day - SAMe donates a methyl group molecule (CH₃) to the enzyme HIOMT that converts the acetylated form of SEROTONIN (NAS) to MELATONIN;

-   Vitamins B6, B12 and folate (folic acid) are essential cofactors of SAMe production

-   At night MELATONIN ▲  ▲  ▲  / SAMe ▼  ▼  ▼  and in the day SAMe ▲  ▲  ▲  / MELATONIN▼  ▼  ▼  - SEROTONIN is also produced at night.

SAMe -And Other Methyl Donor Molecules