title: [Increased activity of PRPP synthetase].
abstract: PRPP(phosphoribosyl pyrophosphate) synthetase catalyzes the formation of PRPP from ATP and ribose 5-phosphate. Human PRPP synthetase exists as heterogeneous aggregates composed of the 34kDa catalytic subunits (PRSI and PRSII) and other 39kDa and 41kDa components designated PRPP synthetase-associated protein (PAP39 and PAP41). A syndrome of increased activity of PRPP synthetase, an X-linked dominant-inherited disorder, is one of the models of gout caused by increased production of uric acid. By now, around twenty cases have been reported over the world. Two different molecular mechanisms underlie this syndrome: (1) point mutation in the gene coding the primary structure of PRPP synthetase causes the substitution of an amino acid residue and, consequently, the regulatory defects, those are resistant traits to allosteric nucleotide feedback inhibition; (2) increased transcription of PRPP synthetase mRNA causes overproduction of this enzyme protein. The mechanism producing increased mRNA is, however, not elucidated. The Japanese case has been found to be caused by the second mechanism.
authors.affiliation: Department of Internal Medicine, Itoh Municipal Hospital.
authors.forename: Taizo
authors.initials: T
authors.lastname: Iizasa
mesh_terms: D041321:Chromosomes, Human, X / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D006073:Gout / Q000145:classification / Q000209:etiology*; D006801:Humans; D017354:Point Mutation; D012333:RNA, Messenger / Q000235:genetics; D012268:Ribose-Phosphate Pyrophosphokinase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D013577:Syndrome; D014158:Transcription, Genetic; D014527:Uric Acid / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014527:Uric Acid; D012268:Ribose-Phosphate Pyrophosphokinase