NAADP+ Synthesis From cADPRP and Nicotinic Acid by ADP-ribosyl Cyclases

Biochem Biophys Res Commun. 2006 Jun 30;345(2):573-80. doi: 10.1016/j.bbrc.2006.04.096. Epub 2006 Apr 27.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase / metabolism*
  • ADP-ribosyl Cyclase 1 / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cyclic ADP-Ribose / analogs & derivatives
  • Cyclic ADP-Ribose / metabolism*
  • Cyclization
  • HL-60 Cells
  • Humans
  • Hydrolysis
  • Kinetics
  • NADP / analogs & derivatives*
  • NADP / chemical synthesis
  • Niacin / metabolism*
  • Tretinoin / metabolism

Substances

  • cyclic ADP-ribose 2'-phosphate
  • Cyclic ADP-Ribose
  • Niacin
  • NADP
  • NAADP
  • Tretinoin
  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1