title: Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn(2+)-dependent ADP-ribose/CDP-alcohol pyrophosphatase.
abstract: Cyclic ADP-ribose (cADPR) metabolism in mammals is catalyzed by NAD glycohydrolases (NADases) that, besides forming ADP-ribose, form and hydrolyze the N(1)-glycosidic linkage of cADPR. Thus far, no cADPR phosphohydrolase was known. We tested rat ADP-ribose/CDP-alcohol pyrophosphatase (ADPRibase-Mn) and found that cADPR is an ADPRibase-Mn ligand and substrate. ADPRibase-Mn activity on cADPR was 65-fold less efficient than on ADP-ribose, the best substrate. This is similar to the ADP-ribose/cADPR formation ratio by NADases. The product of cADPR phosphohydrolysis by ADPRibase-Mn was N(1)-(5-phosphoribosyl)-AMP, suggesting a novel route for cADPR turnover.
authors.affiliation: Grupo de Enzimología, Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Medicina, Universidad de Extremadura, Badajoz, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Canales
authors.forename: Ascensión
authors.initials: A
authors.lastname: Fernández
authors.forename: Joaquim Rui
authors.initials: JR
authors.lastname: Rodrigues
authors.forename: Rui
authors.initials: R
authors.lastname: Ferreira
authors.forename: João Meireles
authors.initials: JM
authors.lastname: Ribeiro
authors.forename: Alicia
authors.initials: A
authors.lastname: Cabezas
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Costas
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Cameselle
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D036563:Cyclic ADP-Ribose / Q000737:chemistry* / Q000378:metabolism; D006868:Hydrolysis; D008345:Manganese / Q000378:metabolism*; D008958:Models, Molecular; D011755:Pyrophosphatases / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity
chemical_list: D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D008345:Manganese; D011755:Pyrophosphatases