Nitric oxide stimulates auto-ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase.
Nitric oxide generation in brain cytosolic fractions markedly enhances ADP-ribosylation of a single 37-kDa protein. By utilizing a biotinylated NAD and avidin affinity chromatography, we purified this protein. Partial amino acid sequencing establishes its identity as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). This is further confirmed by detection of GAPDH enzymatic activity in the purified 37-kDa protein. GAPDH is ADP-ribosylated in the absence of brain extract. This auto-ADP-ribosylation is enhanced by nitric oxide generation. ADP-ribosylation appears to involve the cysteine where NAD interacts with GAPDH so that ADP-ribosylation likely inhibits enzymatic activity. Such inhibition may play a role in nitric oxide-mediated neurotoxicity.
Zhang
J
J
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Snyder
S H
SH
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D003545:Cysteine / Q000737:chemistry; D003600:Cytosol / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009243:NAD / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats
D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009569:Nitric Oxide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D003545:Cysteine