Serotonin Biosynthesis

Serotonin is an example of a monoamine neurotransmitter, a chemical messenger that is passed between nerve cells. This hormone is mainly found in the gastrointestinal tract, the platelets and the central nervous system of animals and is thought to contribute to a sense of well being and happiness.

Serotonin is synthesized from the amino acid L-tryptophan via a short metabolic pathway that involves two major enzymes. These enzymes are:

• Tryptophan hydroxylase (TPH)
• Amino acid decarboxylase

The reaction in this pathway that is mediated by tryptophan hydroxylase is the rate limiting step, meaning that if this enzyme is blocked, the synthesis of serotonin would be stopped. Tryptophan hydroxylase exists in two forms - TPH1 and TPH2. While TPH1 is found in several tissues, TPH2 is specifically found in nerves of the brain.

A serotonin transporter protein called SERT or 5HTT is responsible for carrying serotonin from the synaptic cleft to its target nerve. This transporter acts as a regulator of serotonin levels and mutations in the 5HTT gene have been shown to disrupt serotonin uptake. Serotonin regulates many important bodily functions ranging from sleep, mood, appetite and eating habits as well as influencing anxiety levels, suicidal tendencies, and our ability to learn and memorize things.

The 5-HTT protein is an important target of many antidepressant therapies. There are two forms of 5-HTT genes, the long form and the short form. Studies have shown that people with two long forms of the 5-HTT genes are less likely to suffer from depression compared with people who have one short and one long copy of the gene or two short copies.

While serotonin in its primary form cannot reach the brain since it cannot cross the blood–brain barrier, the serotonin precursors tryptophan and its metabolite 5-hydroxytryptophan (5-HTP) do cross this barrier and reach the brain. These agents can be taken as dietary supplements to increase levels of serotonin in the brain.