In animals including humans, serotonin is synthesized from the amino acid L-tryptophan by a short metabolic pathway consisting of two enzymes: tryptophan hydroxylase (TPH) and amino acid decarboxylase (DDC). The TPH-mediated reaction is the rate-limiting step in the pathway.
TPH has been shown to exist in two forms: TPH1, found in several tissues, and TPH2, which is a brain-specific isoform.
The 5-HTT gene (5-hydroxytryptamine transporter, or SLC6A4 = solute carrier family 6 (neurotransmitter transporter, serotonin), member 4) regulates serotonin. This chemical is found in very low amounts in people diagnosed with depression compared to other people. Serotonin works as a neurotransmitter and helps with the modulation of things such as anger, appetite, sexuality, sleep, mood, and several other things. People with depression often have impaired 5-HTT genes. There are two forms of the 5-HTT gene and everyone has two 5-HTT genes. (Levinson) There is a long form of 5-HTT and a short form of 5-HTT. Research shows that people with both 5-HTT genes being the long form are less likely to become depressed while people with one short and one long or two short forms are more likely to develop depression. Research is still being conducted to find more information. There is also evidence that ovarian hormones can affect the expression of TPH in various species, suggesting a possible mechanism for postpartum depression and premenstrual stress syndrome.
Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the blood-brain barrier. However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, can and do cross the blood-brain barrier. These agents are available as dietary supplements and may be effective serotonergic agents.
One product of serotonin breakdown is 5-Hydroxyindoleacetic acid (5 HIAA), which is excreted in the urine. Serotonin and 5 HIAA are sometimes produced in excess amounts by certain tumors or cancers, and levels of these substances may be measured in the urine to test for these tumors.
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