MDC Scientists discover a second gene for serotonin synthesis

Working with mice, they switched off the gene that produces the enzyme tryptophan hydroxylase, which is responsible for serotonin synthesis. Result: the production of serotonin in the gut was halted, but not that in the brain. The results of this work have now been published by Dr. Diego J. Walther and Dr. Michael Bader in the prestigious American journal „Science“ (Vol. 299, No. 5603, http://www.sciencemag.org)*.

For some 30 years scientists have believed there has to be more than one enzyme for the synthesis of the hormone serotonin. To find it, the researchers used a piece of DNA from the well known tryptophan hydroxylase gene, called TPH1 for short, to search through the entire human genome database and found similar sequence fragments on Chromosome 12. They were able to show that this newly discovered gene is found in all vertebrates and also produces active tryptophan hydroxylase. The enzyme of the new gene, which the researchers call TPH2 for short, is responsible for the synthesis of serotonin in the brain, while the enzyme of the TPH1 gene produces the messenger in the gut. The researchers’ next step is to investigate what happens if they switch off the second gene. They hope that their new findings will open up new ways of targeting treatments for diseases affecting the central nervous system.

*Synthesis of Serotonin by A Second Tryptophan Hydroxylase Isoform
Diego J. Walther¹†, Jens-Uwe Peter¹, Saleh Bashammakh1, Heide Hörtnagl², Mechthild Voits², Heidrun Fink³, Michael Bader¹†

¹Max Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, D-13092 Berlin-Buch, Germany; ²Institute of Pharmacology and Toxicology of the Medical Faculty, Charité, Humboldt University Berlin, Dorotheenstrasse 94, D-10117 Berlin, Germany, ³Institute of Pharmacology and Toxicology of the School of Veterinary Medicine, Free University Berlin, Koserstrasse 20, D-14195 Berlin, Germany

† To whom correspondence and requests for materials should be addressed. Email: dwalther@mdc-berlin.de or mbader@mdc-berlin.de.

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Molecular Biology of Peptide Hormones

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