A unified mechanism of enzymatic synthesis of two calcium messengers: cyclic ADP-ribose and NAADP

Biol Chem. Jul-Aug 1999;380(7-8):785-93. doi: 10.1515/BC.1999.098.


Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) mobilize Ca2+ from two different types of intracellular stores and through completely independent mechanisms. The two Ca2+ messengers are also structurally distinct. cADPR is a cyclic nucleotide derived from NAD, while NAADP is a linear metabolite of NADP. Systems responsive to these two novel signaling molecules are widespread among eukaryotes and include protozoan, plant, invertebrate, mammalian as well as human cells. Despite their functional and structural differences, cADPR and NAADP are sibling messengers synthesized by a single enzyme, ADP-ribosyl cyclase. In this article the recent progress in understanding the physiological roles of cADPR and NAADP is briefly reviewed. A unified mechanism of catalysis is also proposed, which takes into consideration the crystallographic structure of ADP-ribosyl cyclase and accounts for its novel multi-functionality.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Adenosine Diphosphate Ribose / analogs & derivatives*
  • Adenosine Diphosphate Ribose / biosynthesis
  • Adenosine Diphosphate Ribose / chemistry
  • Adenosine Diphosphate Ribose / physiology
  • Animals
  • Antigens, CD*
  • Antigens, Differentiation / metabolism*
  • Calcium / metabolism*
  • Catalysis
  • Cyclic ADP-Ribose
  • Humans
  • Membrane Glycoproteins
  • Molecular Structure
  • NAD+ Nucleosidase / metabolism*
  • NADP / analogs & derivatives*
  • NADP / biosynthesis
  • NADP / chemistry
  • NADP / physiology


  • Antigens, CD
  • Antigens, Differentiation
  • Membrane Glycoproteins
  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • NADP
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1
  • Calcium