NAADP+ synthesis from cADPRP and nicotinic acid by ADP-ribosyl cyclases.
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.
Moreschi
Iliana
I
Department of Experimental Medicine, Section of Biochemistry, and Center of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV/1, 16132 Genova, Italy.
Bruzzone
Santina
S
Melone
Luca
L
De Flora
Antonio
A
Zocchi
Elena
E
D036541:ADP-ribosyl Cyclase / Q000378:metabolism*; D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D036563:Cyclic ADP-Ribose / Q000031:analogs & derivatives / Q000378:metabolism*; D003500:Cyclization; D018922:HL-60 Cells; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D009249:NADP / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009525:Niacin / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism
C098663:cyclic ADP-ribose 2'-phosphate; D036563:Cyclic ADP-Ribose; D009525:Niacin; D009249:NADP; C024376:NAADP; D014212:Tretinoin; D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1