Drosophila GTP Cyclohyrodrolase: Multiple Isoform Products of a Single Gene Derive from Alternate Transcripts that are Developmentally Regulated and Functionally Specific

Abstract

GTP cyclohydrolase I (GTP CH) in Drosophila melanogaster is strikingly similar to its mammalian cognates by deduced protein homology as well as by biochemical mechanisms (1, 2; McLean, Krishnakumar and O’Donnell, submitted). As in mammals, GTP CH is the first and rate-limiting enzyme in the synthesis of pteridines; beyond the catalytic properties of the enzyme, the products of the pathway initiated by this enzyme share functional roles. For example, the aromatic amino acid hydroxylases in Drosophila require a pteridine cofactor for enzymatic activity (3, 4). The diversity of pteridine functions in multicellular organisms necessitates a complexity of regulatory mechanisms. In order to understand this complexity, an in vivo model is essential. The powerful molecular genetics of Drosophila make it a cogent system for such studies.