Bovine liver mitochondrial NAD+ glycohydrolase. Relationship to ADP-ribosylation and calcium fluxes.
Mitochondrial NAD+ glycohydrolase (NADase) has been proposed to be required for (nonenzymatic) ADP-ribosylation and subsequent activation of a Ca2+ release pathway. In our studies it has been found that several agents including nicotinamide, dithiothreitol, and EDTA exert no or little effect on ADP-ribosylation in isolated bovine liver mitochondria, while strongly inhibiting the NADase. The NADase did, however, catalyze the formation of cyclic purine nucleoside diphosphoriboses (similar to cyclic ADP-ribose) from NAD+ analogs. It appears possible, therefore, that this enzyme may be involved in the regulation of mitochondrial Ca2+ fluxes by forming a potent Ca(2+)-mobilizing agent, rather than by providing the substrate for non-enzymatic ADP-ribosylation.
Ziegler
M
M
Freie Univ. Berlin, Institut f. Biochemie, Germany.
Jorcke
D
D
Herrero-Yraola
A
A
Schweiger
M
M
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D004229:Dithiothreitol / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006156:Guanosine Diphosphate Sugars / Q000096:biosynthesis; D015636:Magnesium Chloride / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000201:enzymology*; D009243:NAD / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*
D004791:Enzyme Inhibitors; D006156:Guanosine Diphosphate Sugars; C090657:cyclic guanosine diphosphate-ribose; D015636:Magnesium Chloride; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D009244:NAD+ Nucleosidase; D002118:Calcium; D004229:Dithiothreitol