NAD hydrolysis: chemical and enzymatic mechanisms.
The pyridine nucleotides have important non-redox activities as cellular effectors and metabolic regulators [1-3]. The enzyme-catalyzed cleavage of the nicotinamide-ribosyl bond of NAD+ and the attendant delivery of the ADPRibosyl moiety to acceptors is central to these many diverse biological activities. Included are the medically important NAD-dependent toxins associated with cholera, diphtheria, pertussis, and related diseases [4]; the reversible ADPRibosylation-mediated biological regulatory systems [5,6]; the synthesis of poly(ADPRibose) in response to DNA damage or cellular division [7]; and the synthesis of cyclic ADPRibose as part of an independent, calcium-mediated regulatory system [8]. As will be presented in this chapter, all evidence points to both the chemical and enzyme-catalyzed cleavage of the nicotinamide-ribosyl bond being dissociative in character via an oxocarbenium intermediate.
Oppenheimer
N J
NJ
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-0446.
D000818:Animals; D002384:Catalysis; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D009243:NAD / Q000378:metabolism*; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013379:Substrate Specificity
D009243:NAD; D009244:NAD+ Nucleosidase