Different properties of the central and peripheral forms of human tryptophan hydroxylase.
Tryptophan hydroxylase (TPH) catalyses the rate-limiting reaction in the biosynthesis of serotonin. In humans, two different TPH genes exist, located on chromosomes 11 and 12, respectively, and encoding two enzymes (TPH1 and TPH2) with an overall sequence identity of 71%. We have expressed both enzymes as various fusion proteins in Escherichia coli and using an in vitro transcription/translation system, and compared their solubility and kinetic properties. TPH2 is more soluble than TPH1, has a higher molecular weight and different kinetic properties, including a lower catalytic efficiency towards phenylalanine than TPH1. Both enzymes are phosphorylated by cAMP-dependent protein kinase A. TPH2 was phosphorylated at Ser19, a phosphorylation site not present in TPH1. The differences between TPH1 and TPH2 have important implications for the regulation of serotonin production in the brain and the periphery and may provide an explanation for some of the diverging results reported for TPH from different sources in the past.
McKinney
Jeffrey
J
Department of Biomedicine, Section of Biochemistry and Molecular Biology, University of Bergen, Bergen, Norway.
Knappskog
Per M
PM
Haavik
Jan
J
D048948:14-3-3 Proteins / Q000737:chemistry / Q000378:metabolism; D004795:Enzyme Stability / Q000502:physiology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D007700:Kinetics; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D012995:Solubility; D013379:Substrate Specificity; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics
D048948:14-3-3 Proteins; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D014365:Tryptophan Hydroxylase