How is melatonin made?

Are you feeling sleep-deprived? Do you toss and turn all night, counting fluffy sheep without a woolly ending in sight? Well, worry not my friend because melatonin is here to help with our darling children – the Pineal Glands. You might wonder how this magical hormone that promotes sleep comes into being. This article will take you on a journey of discovery through your brain, discussing what happens between your neurons to create the little-known but vital molecule we all call melatonin.

The Production of Melatonin

Melatonin is produced in the pineal gland present in the center of our heads that carries out important functions such as regulating wake-sleep cycles and making dreamy-dreams come true. Here’s a brief overview of everything happening within this crucial pea-sized structure:

  1. Darkness: Once darkness descends upon us, it signals our body-clock (or Circadian Rhythm) located somewhere deep inside your suprachiasmatic nuclei right above your nose bridge.

  2. Command Central: It sends an unfailing signal straight down to our dear Pineal Gland situated right where those rhymes tend to live rent-free only allowing for valuable tenants like melatonin production.

  3. Enzymes Start their Biggest Job Yet: A well-awaited reaction kicks off between metabolites called tryptophan and serotonin via enzymes pyridoxal-5-phosphate or P5P for short and serotonin N-acetyltransferase (AANAT), which takes care of it from then onwards.

  4. Take their Own Time Slowing Down Reactions After 30 Mins… approximately:YLAEK Once set up at melody-making speeds around every thirty minutes, they reach maximum speed when left undisturbed by harmful stimuli while peacefully pursuing mystical growth!

After reading over all these words detailing how amazing each step has been so far worth reading more of this exciting synthesis pathway on what comes next! So let us continue in the same energy shall we?

The Chemical Pathway

As previously established, melatonin starts off as tryptophan which turns into serotonin after interacting with an enzyme. Then another molecular modification occurs via yet another group of enzymes and voila – melatonin that promotes sleep and regulates our body’s natural clock is produced!

Tryptophan -> Serotonin:

Tryptophan undergoes hydroxylation through the action of two well-known and sturdy accomplices in their greater scheme namely tetrahydrobiopterin (BH4) ensuring it plays a role later down history rather than not doing anything too important upfront.

First Step: Hydroxylation by TPH1

If you’re wondering who bathes each molecule to dissolve grime away look no further than TPH – tryptophan hydroxylase 1 chances are they own stock options for soapy water already!)

Second Step: Decarboxylation by AADC

Decarboxylases catalyze removing any carbon dioxide groups from amino acids left behind while oxygens keep putting up stinks about how “NO ONE washes me anymore”.

Both pathways provide a prescriptive sequence wherein essential components can be isolated properly. Eventually, Serotonin is finally made this way- YAY.


Now let’s talk about those other changes required for serotonins metamorphosis into melatonin proper(a syntatic frankensteining rooted in evolution-don’t worry that term was my greatest discovery).

The development process depends on three incredibly tough components where all have complicated vague names so stick with me here as I unravel them one by one:

Milligrams matter:

The concentration required enough of both methionine adenosyl transferase or MAT (responsible for capping certain sulfides to provide those necessary bonds) and acetylserotonin O-methyltransferases or ASMT (responsible for adding a methylate too to the molecule that causes epigenetic changes) to combine everything needed time-wise.

Little bit o’ energy:

Additionally, this reaction requires more than just chemical help. It also needs energy! This requirement comes mostly from reduced nicotinamide adenine dinucleotide phosphate or NADPH which is used in reactions like this one!

Structure determination

Last but not least we have hydroxyindole-O-methyltransferease(HIOMT), which acts as our sword-wielding hero adeptly chopping away where only few enzymes dare dream of touching thereby making our melatonin production dreams become reality.

This perfect trifecta ultimately creates melatonin that invites you on a peaceful journey through droopy eyes and into blissful dreamland because it’s hard work being an extra hormone for your body(we’ll call it providing ZzZ’s).


In conclusion, the synthesis pathway of melatonin in Pineal gland stands full of intricacies. There are profs tripping over themselves trying desperately to understandwhat makes melatonin works so well(yes even myself am guilty about wondering). But all said and done – with dark sets come sleepies let us welcome them with open arms ready for another beautiful sunrise soon enough thanks to some simple metabolic pathways!


  • Melatonin is produced by Pineal gland.
  • Darkness activates Circadian rhythm signaling Pineal Glands.
  • Tryptophan converted via serotonin helps create foundation layer essential components.
  • Hydroxylation via TPH1 & decarboxylation using AADC converted tryptophan molecule into serotonin thereafter designated Methionine Adenosyl Transferase (MAT) capped sulfides order mixed nucleobases together linking resultant output resembling sheets, creating compound later degraded into homocysteine.
  • Simultaneously, Acetylserotonin O-methyltransfer is involved with adding a methylate ion to serotonin which lends itself towards making sure epigenetic changes take place.
  • Energy is needed via NADPH for the reaction only done in the pineal gland.
  • Hydroxyindole-O-methyltransferease (HIOMT) catalyzes nearly final stage in ensuring melatonin dream comes true.

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