Serotonin metabolism (5-HT metabolism)

Serotonin metabolism refers to the integrated biochemical pathway responsible for the synthesis, transport, and degradation of the monoamine neurotransmitter 5-hydroxytryptamine (5-HT). The pathway begins with the rate-limiting conversion of L-tryptophan to 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan hydroxylase (TPH), followed by decarboxylation to serotonin via aromatic L-amino acid decarboxylase (StatPearls, 2023). Serotonin is primarily inactivated through enzymatic oxidation by monoamine oxidase A (MAO-A) into 5-hydroxyindoleacetic acid (5-HIAA) or through sequestration by the serotonin transporter (UniProt P21397; UniProt P31645). Dysregulation of this metabolic balance is a hallmark of various psychiatric conditions, such as depression and anxiety, as well as peripheral disorders like carcinoid syndrome and irritable bowel syndrome (NIH, 2023). Therapeutic agents target various nodes of this metabolism, including MAO inhibitors (MAOIs) to prevent degradation and TPH inhibitors like telotristat to limit overproduction in systemic diseases (PubChem). Because 'Serotonin metabolism' describes a complex biological process involving multiple enzymes and transporters rather than a single molecular target, it is classified as a pathway rather than a discrete drug target.

Other names

5-Hydroxytryptamine metabolismSerotonergic pathwaySerotonin turnoverSerotonin biosynthesis and degradation

Inhibition of tryptophan hydroxylase (TPH) to reduce serotonin synthesis; Inhibition of monoamine oxidase (MAO) to decrease serotonin degradation; Inhibition of the serotonin transporter (SERT) to prevent reuptake.