Hydrolysis of the phosphoanhydride linkage of cyclic ADP-ribose by the Mn(2+)-dependent ADP-ribose/CDP-alcohol pyrophosphatase

FEBS Lett. 2009 May 19;583(10):1593-8. doi: 10.1016/j.febslet.2009.04.023. Epub 2009 Apr 18.

Abstract

Cyclic ADP-ribose (cADPR) metabolism in mammals is catalyzed by NAD glycohydrolases (NADases) that, besides forming ADP-ribose, form and hydrolyze the N(1)-glycosidic linkage of cADPR. Thus far, no cADPR phosphohydrolase was known. We tested rat ADP-ribose/CDP-alcohol pyrophosphatase (ADPRibase-Mn) and found that cADPR is an ADPRibase-Mn ligand and substrate. ADPRibase-Mn activity on cADPR was 65-fold less efficient than on ADP-ribose, the best substrate. This is similar to the ADP-ribose/cADPR formation ratio by NADases. The product of cADPR phosphohydrolysis by ADPRibase-Mn was N(1)-(5-phosphoribosyl)-AMP, suggesting a novel route for cADPR turnover.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate Ribose / chemistry*
  • Adenosine Diphosphate Ribose / metabolism
  • Animals
  • Cyclic ADP-Ribose / chemistry*
  • Cyclic ADP-Ribose / metabolism
  • Hydrolysis
  • Manganese / metabolism*
  • Models, Molecular
  • Pyrophosphatases / chemistry*
  • Pyrophosphatases / metabolism
  • Rats
  • Substrate Specificity

Substances

  • Cyclic ADP-Ribose
  • Adenosine Diphosphate Ribose
  • Manganese
  • Pyrophosphatases