title: Inositol hexakisphosphate kinase products contain diphosphate and triphosphate groups.
abstract: Eukaryotic cells produce a family of diverse inositol polyphosphates (IPs) containing pyrophosphate bonds. Inositol pyrophosphates have been linked to a wide range of cellular functions, and there is growing evidence that they act as second messengers. Inositol hexakisphosphate kinase (IP6K) is able to convert the natural substrates inositol pentakisphosphate (IP 5) and inositol hexakisphosphate (IP 6) to several products with an increasing number of phospho-anhydride bonds. In this study, we structurally analyzed IPs synthesized by three mammalian isoforms of IP6K from IP 5 and IP 6. The NMR and mass analyses showed a number of products with diverse, yet specific, stereochemistry, defined by the architecture of IP6K's active site. We now report that IP6K synthesizes both pyrophosphate (diphospho) as well as triphospho groups on the inositol ring. All three IP6K isoforms share the same activities both in vitro and in vivo.
authors: Department of Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
authors: Petra
authors: P
authors: Draskovic
authors: Adolfo
authors: A
authors: Saiardi
authors: Rashna
authors: R
authors: Bhandari
authors: Adam
authors: A
authors: Burton
authors: Gregor
authors: G
authors: Ilc
authors: Miroslav
authors: M
authors: Kovacevic
authors: Solomon H
authors: SH
authors: Snyder
authors: Marjetka
authors: M
authors: Podobnik
mesh_terms: D002101:Cacodylic Acid / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D011756:Diphosphates / Q000032:analysis* / Q000737:chemistry*; D007295:Inositol Phosphates / Q000737:chemistry / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D013058:Mass Spectrometry; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010833:Phytic Acid / Q000737:chemistry / Q000378:metabolism; D011122:Polyphosphates / Q000032:analysis* / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D011756:Diphosphates; D007295:Inositol Phosphates; D007527:Isoenzymes; D011122:Polyphosphates; C402123:inositol heptakisphosphate; C079849:1-diphosphoinositol pentakisphosphate; D010833:Phytic Acid; D002101:Cacodylic Acid; D017856:Phosphotransferases (Phosphate Group Acceptor); C099438:inositol hexakisphosphate kinase; C005692:triphosphoric acid