Synthesis and Properties of Serotonin

In the central nervous system (CNS), serotonin modulates various functions such as mood, appetite, sleep, learning, and memory. Serotonin also exists in the enteric nervous system located in the gastrointestinal tract and regulates intestinal functions. Serotonin secreted in the blood is bound to platelets and regulates vasoconstriction and blood clotting.

Structure

Molecular formula, C10H12N2O. Serotonin is an indoleamine molecule derived from tryptophan. Tryptophan is hydroxylated at position 5 of the ring forming 5-hydroxytryptophan and decarboxylated to form serotonin.

Properties

Mr 176.21. Serotonin is soluble in water (25.5mg/mL). Serotonin does not cross the blood-brain barrier. 

Synthesis and release

Gene, mRNA, and precursor L-Tryptophan is hydroxylated to form 5-hydroxy-L-tryptophan (5-HTP) by tryptophan hydroxylase (TPH, L-Tryptophan-5-monooxygenase), which is the rate-limiting step. Two isoforms of TPH are identified. TPH1 is found in several tissues, and TPH2 is the neuron-specific form.5-HPT is decarboxylated by aromatic L-amino acid decarboxylase (5-hydroxytryptophan decarboxylase) and the coenzyme pyridoxal phosphate. 

Tissue distribution of mRNA

In the CNS, serotonin is produced in the raphe nuclei of the midbrain. Serotonergic neurons project to almost every part of the central nervous system. Serotonin also exists in the enteric nervous system. A majority of serotonin (90%) is located in the enterochromaffin cells in the gastrointestinal tract. Serotonin secreted in the blood is bound to platelets. 

Plasma concentration

Humans, 3.3–20.5 nM; Rat, 34.7 nM. In humans, 9.55 nM is the first discriminator to stratify the risk for the presence of coronary microvascular dysfunction.

Regulation of synthesis and release

Synthesis of 5-HTP by TPH is the rate-limiting step in serotonin synthesis. The action of serotonin in the synapse is terminated via the uptake of serotonin by the specific monoamine transporter for serotonin, serotonin transporter (SERT), in the presynaptic neuron.

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