The structure of serotonin

 

Submitted By Shamal Gunawardhana

Edited by Michael Ingram, MD

 

Serotonin is commonly known as the happy chemical but it is much more than just a “happy molecule.” Serotonin functions as a neurotransmitter in the central nervous system as well as a hormone in the periphery. The scientific name for serotonin is 5-Hydroxytryptamine (or its much easier abbreviated form 5-HT).

Building Blocks

Serotonin is biologically derived from the amino acid L-tryptophan. Tryptophan is an essential amino acid; therefore it must be obtained from our diet.

The structure of the serotonin molecule is derived from its precursor amino acid tryptophan and follows the basic blueprint of amino acids.

The basic structure of an amino acid consists of a central alpha carbon atom joined by an amino group, carboxylic acid group, hydrogen atom and an ‘R’ side chain, a variable.

For tryptophan, the R group consist of a methyl group (-CH2-) joined by an indole ring. Indole ring is a bicyclic structure formed by the fusion of a benzene ring and a pyrrole ring, which is essentially a pentameric aromatic ring containing 4 carbon atoms and a single nitrogen atom.

Benzene is a hexameric aromatic ring containing 6 carbon atoms. Adding one of these benzene structures to the side of the pyrrole ring gives us the indole ring.

The structure of serotonin can also be understood by studying its biosynthesis pathway. We can start with our amino acid tryptophan…

 

5HT Here We Come…

 

Serotonin is produced in a multi-step pathway. When producing 5-HT from tryptophan two key changes occur in the structure of the tryptophan molecule–hydroxylation followed by decarboxylation.

 

Hydroxylation

 

Hydroxylation entails the addition of a “hydroxy” group (-OH) to the 5th position of the tryptophan structure.  Wait…but where is the 5th position? This is where numbering the carbon atoms of this structure becomes essential (see diagram below).

Thanks to the laws of chemical nomenclature (beyond the scope of this post), we found the 5th position within the tryptophan structure and now we can add the -OH (hydroxyl) group to this position.

 

Voilà!

 

We have 5-Hydroxytryptophan.

 

This reaction is catalyzed by the appropriately named enzyme Tryptophan 5 hydroxylase(Tph).

 

This is the rate-limiting step of serotonin biosynthesis.

Decarboxylation

 

This step is fairly simple we just have to remove the CO2 group bound to the alpha carbon of the amino acid.

 

This step is catalyzed by the enzyme aromatic L-amino acid decarboxylase.

 

SEROTONIN IN THE GUT

 

There are 2 genes coding for the Tph(Tryptophan 5 hydroxylase) enzyme: Tph1 and Tph2. Tph1 is expressed mostly in enterochromaffin cells of the gut and is responsible for most of the serotonin present in the blood.

 

On the other hand, the gene Tph2 is expressed exclusively in serotonergic neurons of the brainstem(Raphe nuclei) and is responsible for the production of serotonin in the brain.

 

These two pools of serotonin, one in the blood and the other in the brain, never cross over; therefore these should be viewed from a functional point of view as two distinct molecules.

 

Brain-derived serotonin (BDS) acts as a neurotransmitter, while gut-derived serotonin (GDS) acts as a hormone and regulates a wide variety of processes.

Shamal Gunawardhana

Shamal Gunawardhana

Thank you to Shamal for submitting this post!

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