Nitric oxide causes ADP-ribosylation and inhibition of glyceraldehyde-3-phosphate dehydrogenase.
Nitric oxide and nitric oxide-generating agents like 3-morpholinosydnonimine (SIN-1) stimulate the mono-ADP-ribosylation of a cytosolic, 39-kDa protein in various tissues. This protein was purified from human platelet cytosol by conventional and fast protein liquid chromatography techniques. N-terminal sequence analysis identified the isolated protein as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Nitric oxide stimulates the auto-ADP-ribosylation of GAPDH in a time and concentration-dependent manner with maximal effects after about 60 min. Associated with ADP-ribosylation is a loss of enzymatic activity. NAD(+)-free enzyme is not inhibited by SIN-1, indicating the absolute requirement of NAD+ as the substrate of the ADP-ribosylation reaction. Inhibition of the glycolytic enzyme GAPDH may be relevant as a cytotoxic effect of NO complementary to its inhibitory actions on iron-sulfur enzymes like aconitase and electron transport proteins of the respiratory chain.
Dimmeler
S
S
Universität Konstanz, Fakultät für Biologie, Federal Republic of Germany.
Lottspeich
F
F
Brüne
B
B
D000246:Adenosine Diphosphate Ribose / Q000097:blood; D001792:Blood Platelets / Q000201:enzymology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors / Q000097:blood* / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009243:NAD / Q000097:blood*; D009569:Nitric Oxide / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases