Wide distribution of an enzyme that catalyzes the hydrolysis of cyclic ADP-ribose.
Cyclic ADP-ribose (cADPR) is a metabolite of NAD+ that is as effective as inositol trisphosphate in mobilizing intracellular-Ca2+ stores. Its synthesizing enzyme, ADP-ribosyl cyclase, has been shown to be present in mammalian and invertebrate tissues. In this study we identify another widely-distributed enzyme that can hydrolyze cADPR to ADP-ribose. Incubation of cADPR with brain extracts resulted in progressive decrease in its Ca2+ mobilizing activity. The degradation of cADPR was catalyzed by a heat-labile protein factor in the brain extracts. Analysis by HPLC indicated a single degradation product was produced in equal molar quantity and that it has identical elution time as ADP-ribose. Proton NMR confirmed that the product was ADP-ribose. The degradation enzyme had a Michaelis constant of 0.16 mM and a broad pH maximum around neutrality. Centrifugation studies of the total brain extracts showed that the degradation activity was membrane-bound. Survey of tissues from various animals established that both the degradation and the synthesizing enzyme of cADPR were widely distributed from mammals to invertebrates. Since the degradation enzyme hydrolyzes an unique linkage between the adenine group and the terminal ribosyl moiety of cADPR, we propose to call it cyclic ADP-ribose hydrolase.
Department of Physiology, University of Minnesota, Minneapolis 55455.
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D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis* / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000201:enzymology; D002118:Calcium / Q000378:metabolism; D002642:Chick Embryo; D036563:Cyclic ADP-Ribose; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D009699:N-Glycosyl Hydrolases / Q000032:analysis* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D012617:Sea Urchins
D015703:Antigens, CD; D000943:Antigens, Differentiation; D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium