NAD HYDROLYSIS - CHEMICAL AND ENZYMATIC MECHANISMS

The pyridine nucleotides have important non-redox activities as cellul ar effecters and metabolic regulators [1-3]. The enzyme-catalyzed clea vage of the nicotinamide-ribosyl bond of NAD(+) and the attendant deli very of the ADPRibosyl moiety to accepters is central to these many di verse biological activities. Included are the medically important NAD- dependent toxins associated with cholera, diphtheria, pertussis, and r elated diseases [4]; the reversible ADPRibosylation-mediated biologica l regulatory systems [5,6]; the synthesis of poly(ADPRibose) in respon se to DNA damage or cellular division [7]; and the synthesis of cyclic ADPRibose as part of an independent, calcium-mediated regulatory syst em[8]. As will be presented in this chapter, all evidence points to bo th the chemical and enzyme-catalyzed cleavage of the nicotinamide-ribo syl bond being dissociative in character via an oxocarbenium intermedi ate.