NAADP+ synthesis from cADPRP and nicotinic acid by ADP-ribosyl cyclases.

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Moreschi I, Bruzzone S, Melone L, De Flora A, Zocchi E

NAADP+ synthesis from cADPRP and nicotinic acid by ADP-ribosyl cyclases.

Biochem Biophys Res Commun. 2006 Jun 30;345(2):573-80. Epub 2006 Apr 27.

PubMed ID
16690024 [ View in PubMed
]
Abstract

ADP-ribosyl cyclases (ADPRCs) are present from lower Metazoa to mammals and synthesize the Ca2+-active (di)nucleotides cyclic ADP-ribose (cADPR), NAADP+, and ADP-ribose (ADPR), involved in the regulation of important cellular functions. NAADP+ can be synthesized by ADPRCs from NADP+ through a base-exchange reaction, which substitutes nicotinamide for nicotinic acid (NA). Here we demonstrate that ADPRCs from both lower and higher Metazoa (including human CD38) can also synthesize NAADP+ starting from 2'-phospho-cyclic ADP-ribose (cADPRP) and NA. Comparison, on the two substrates cADPRP and NADP+, of the relative rates of the reactions introducing NA and hydrolyzing/cyclizing the substrate, respectively, indicates that with all ADPRCs tested cADPRP is preferentially transformed into NAADP+, while NADP+ is preferentially cyclized or hydrolyzed to cADPRP/2'-phospho-ADP-ribose. cADPRP was detectable in retinoic acid-differentiated, CD38+ HL-60 cells, but not in undifferentiated, CD38- cells. These results suggest that cADPRP may be a NAADP+ precursor in ADPRC+ cells.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
NicotinamideADP-ribosyl cyclase 2ProteinHumans
Yes
Product of
Details
Polypeptides
NameUniProt ID
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1P28907Details