title: Involvement of cytosolic NAD+ glycohydrolase in cyclic ADP-ribose metabolism.
abstract: The NAD+ glycohydrolase homogeneously purified from bovine brain cytosol was found to catalyze the synthesis and hydrolysis of cyclic ADP-ribose (cADPR). Although the formation of cADPR from NAD+ does not exceed about 2% of the reaction products, the cyclase activity is clearly evidenced by its conversion of NGD+ to cyclic GDP-ribose (cGDPR), which cannot be hydrolyzed to GDPR. Importantly, a steep increase in cADPR hydrolytic activity was observed at cADPR concentrations above 60 microM, which could be reproduced on a Hill curve with a Hill coefficient of 2. Thus, the allosteric binding of cADPR to the NAD+ glycohydrolase (E) molecule promotes the hydrolysis of cADPR. These results suggest that NAD+ hydrolysis to ADPR and nicotinamide catalyzed by the NAD+ glycohydrolase occurs through the formation of a cADPR. E. cADP-ribosyl complex. The low production of cADPR by NAD+ glycohydrolase compared with invertebrate ADP-ribosyl cyclase is believed to be attributable to the fast hydrolysis of cADPR by the allosteric effect of cADPR bound to the same enzyme that produces it.
authors.affiliation: Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Matsumura
authors.forename: S
authors.initials: S
authors.lastname: Tanuma
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism; D000495:Allosteric Site; D000818:Animals; D001921:Brain / Q000201:enzymology; D002417:Cattle; D036563:Cyclic ADP-Ribose; D003600:Cytosol / Q000201:enzymology*; D004789:Enzyme Activation; D006868:Hydrolysis; D007700:Kinetics; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D009243:NAD; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; C090939:GDP-ribosyl cyclase; D009699:N-Glycosyl Hydrolases; D009244:NAD+ Nucleosidase