title: Understanding inositol pyrophosphate metabolism and function: kinetic characterization of the DIPPs.
abstract: We illuminate the metabolism and the cell-signaling activities of inositol pyrophosphates, by showing that regulation of yeast cyclin-kinase by 1-InsP7 is not conserved for mammalian CDK5, and by kinetically characterizing Ddp1p/DIPP-mediated dephosphorylation of 1-InsP7, 5-InsP7 and InsP8. Each phosphatase exhibited similar Km values for every substrate (range: 35-148 nM). The rank order of kcat values (1-InsP7>5-InsP7=InsP8) was identical for each enzyme, although DIPP1 was 10- to 60-fold more active than DIPP2α/β and DIPP3α/β. We demonstrate InsP8 dephosphorylation preferentially progresses through 1-InsP7. Conversely, we conclude that the more metabolically and functionally significant steady-state route of InsP8 synthesis proceeds via 5-InsP7.
authors.affiliation: Department of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV11LY, UK.
authors.forename: Rajagopal S
authors.initials: RS
authors.lastname: Kilari
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Weaver
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Shears
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Safrany
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism
chemical_list: D007295:Inositol Phosphates; C402123:inositol heptakisphosphate; D017766:Acid Anhydride Hydrolases; C116368:diphosphoinositol polyphosphate phosphohydrolase
keywords: CDK5RAP1; Diphosphoinositol; Nudix; Phosphohydrolase
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