Serotonin (5-hydroxytryptamine – 5-HT) is a key neurotransmitter with multiple roles, both in the brain and in peripheral tissues such as the gut and blood vessels. One of the rate-limiting enzymes in 5-HT synthesis is tryptophan hydroxylase (TPH) — for which no tissue specific isoforms have been identified. In the January 3 Science, Diego J. Walther and colleagues at the Max Delbrück Center for Molecular Medicine, Berlin, Germany, show that serotonin can be synthesized by a second tryptophan hydroxylase isoform exclusively in the brain (Science, 299:76, January 3, 2003).

Walther et al. generated mice genetically deficient for tryptophan hydroxylase (Tph-/-) and observed that these mice showed no change in behavior and had normal amounts of 5-HT in the brain, but lacked peripheral 5-HT — except for in the duodenum. In addition, they obtained a full-length cDNA of a brain isoform for Tph (Tph2), which...

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