title: Involvement of bovine spleen NAD+ glycohydrolase in the metabolism of cyclic ADP-ribose-mechanism of the cyclization reaction.
abstract: We have shown that highly purified bovine spleen NAD+ glycohydrolase (NADase), known so far to catalyze the hydrolysis of the nicotinamide-ribose bond of NAD(P)+, was also able to convert NAD+ into cyclic ADP-ribose (cADPR) and to hydrolyze cADPR into ADP-ribose. The kinetic parameters measured for the cyclic ADP-ribose hydrolase activity seem to exclude that cADPR is a kinetically competent reaction intermediate in the NADase catalyzed conversion of NAD+ into ADP-ribose. The cyclase activity of bovine NADase was best evidenced by the transformation of NGD+ into cyclic GDP-ribose which was the major reaction product whereas, in contrast, cADPR accounted for less than 2% of the products formed. For the formation of cADPR we propose a reaction mechanism that is based on the partitioning of an oxocarbenium reaction intermediate between an intramolecular attack by the N1-position of adenine and an intramolecular reaction by a water molecule. Accordingly, the difference in cyclization between NAD+ and NGD+ is accounted for by the difference in reactivity of the N1 and N7 positions of the purine ring in these dinucleotides.
authors.affiliation: Laboratoire de Chimie Bioorganique, URA CNRS 1386, Faculté de Pharmacie, Illkirch, France.
authors.forename: H
authors.initials: H
authors.lastname: Muller-Steffner
authors.forename: A
authors.initials: A
authors.lastname: Augustin
authors.forename: F
authors.initials: F
authors.lastname: Schuber
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D002384:Catalysis; D002417:Cattle; D036563:Cyclic ADP-Ribose; D006868:Hydrolysis; D000432:Methanol / Q000378:metabolism; D015394:Molecular Structure; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000737:chemistry / Q000378:metabolism*; D013154:Spleen / Q000201:enzymology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D000432:Methanol