SYNTHESIS AND DEGRADATION OF CYCLIC ADP RIBOSE BY NAD GLYCOHYDROLASES

Cyclic adenosine diphosphoribose (cADPR), a recently discovered metabo lite of nicotinamide adenine dinucleotide (NAD), is a potent calcium-r eleasing agent postulated to be a new second messenger. An enzyme that catalyzes the synthesis of cADPR from NAD and the hydrolysis of cADPR to ADP-ribose (ADPR) was purified to homogeneity from canine spleen m icrosomes. The net conversion of NAD to ADPR categorizes this enzyme a s an NAD glycohydrolase. NAD glycohydrolases are ubiquitous membrane-b ound enzymes that have been known for many years but whose function ha s not been identified. The results presented here suggest that these e nzymes may function in the regulation of calcium homeostasis by the ab ility to synthesize and degrade cADPR.