Serotonin synthesis by two distinct enzymes in Drosophila melanogaster
Article first published online: 8 APR 2005
Copyright © 2005 Wiley-Liss, Inc.
Archives of Insect Biochemistry and Physiology
Volume 59, Issue 1, pages 12–31, May 2005
How to Cite
Coleman, C. M. and Neckameyer, W. S. (2005), Serotonin synthesis by two distinct enzymes in Drosophila melanogaster. Arch. Insect Biochem. Physiol., 59: 12–31. doi: 10.1002/arch.20050
- Issue published online: 8 APR 2005
- Article first published online: 8 APR 2005
- Manuscript Accepted: 11 JAN 2005
- Manuscript Received: 15 SEP 2004
- NIGMS. Grant Number: T32 GM008306
- aromatic amino acid hydroxylase;
- tryptophan hydroxylase
Annotation of the sequenced Drosophila genome suggested the presence of an additional enzyme with extensive homology to mammalian tryptophan hydroxylase, which we have termed DTRH. In this work, we show that enzymatic analyses of the putative DTRH enzyme expressed in Escherichia coli confirm that it acts as a tryptophan hydroxylase but can also hydroxylate phenylalanine, in vitro. Building upon the knowledge gained from the work in mice and zebrafish, it is possible to hypothesize that DTRH may be primarily neuronal in function and expression, and DTPH, which has been previously shown to have phenylalanine hydroxylation as its primary role, may be the peripheral tryptophan hydroxylase in Drosophila. The experiments presented in this report also show that DTRH is similar to DTPH in that it exhibits differential hydroxylase activity based on substrate. When DTRH uses tryptophan as a substrate, substrate inhibition, catecholamine inhibition, and decreased tryptophan hydroxylase activity in the presence of serotonin synthesis inhibitors are observed. When DTRH uses phenylalanine as a substrate, end product inhibition, increased phenylalanine hydroxylase activity after phosphorylation by cAMP-dependent protein kinase, and a decrease in phenylalanine hydroxylase activity in the presence of the serotonin synthesis inhibitor, α-methyl-DL-tryptophan are observed. These experiments suggest that the presence of distinct tryptophan hydroxylase enzymes may be evolutionarily conserved and serve as an ancient mechanism to appropriately regulate the production of serotonin in its target tissues. Arch. Insect Biochem. Physiol. 59:12–31, 2005. © 2005 Wiley-Liss, Inc.