TY - JOUR
T1 - Structures and activities of cyclic ADP-ribose, NAADP and their metabolic enzymes
AU - Lee, Hon Cheung
AU - Munshi, Cyrus
AU - Graeff, Richard M
PY - 1999
Y1 - 1999
N2 - ADP-ribosyl cyclase and CD38 are multi-functional enzymes involved in calcium signaling. Both can cyclize NAD and its guanine analog, NGD, at two different sites of the purine ring, N1 and N7, respectively, to produce cyclic ADP-ribose (cADPR) and cyclic GDP-ribose, a fluorescent but inactive analog. Both enzymes can also catalyze the exchange of the nicotinamide group of NADP with nicotinic acid, producing yet another potent activator of Ca2+ mobilization, nicotinic acid adenine dinucleotide phosphate (NAADP). The Ca2+ release mechanism activated by NAADP is totally independent of cADPR and inositol trisphosphate indicating it is a novel and hitherto unknown Ca2+ signaling pathway. This article summarizes the current results on the structures and activities of cADPR, NAADP and the enzymes that catalyze their syntheses. A comprehensive model accounting for the novel multi-functionality of ADP-ribosyl cyclase and CD38 is presented.
AB - ADP-ribosyl cyclase and CD38 are multi-functional enzymes involved in calcium signaling. Both can cyclize NAD and its guanine analog, NGD, at two different sites of the purine ring, N1 and N7, respectively, to produce cyclic ADP-ribose (cADPR) and cyclic GDP-ribose, a fluorescent but inactive analog. Both enzymes can also catalyze the exchange of the nicotinamide group of NADP with nicotinic acid, producing yet another potent activator of Ca2+ mobilization, nicotinic acid adenine dinucleotide phosphate (NAADP). The Ca2+ release mechanism activated by NAADP is totally independent of cADPR and inositol trisphosphate indicating it is a novel and hitherto unknown Ca2+ signaling pathway. This article summarizes the current results on the structures and activities of cADPR, NAADP and the enzymes that catalyze their syntheses. A comprehensive model accounting for the novel multi-functionality of ADP-ribosyl cyclase and CD38 is presented.
KW - Ca
KW - Cyclic ADP-ribose (cADPR)
KW - Nicotinic acid adenine dinucleotide phosphate (NAADP)
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U2 - 10.1007/978-1-4419-8740-2_13
DO - 10.1007/978-1-4419-8740-2_13
M3 - Article
C2 - 10331643
AN - SCOPUS:0032945168
SN - 0300-8177
VL - 193
SP - 89
EP - 98
JO - Molecular and cellular biochemistry
JF - Molecular and cellular biochemistry
IS - 1-2
ER -