Glyceraldehyde-3-phosphate activates auto-ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase

• Published in: FEBS letters 1993-06, Vol.324 (1), p.33-36
• Main Authors: Kots, Alexander Ya, Sergienko, Edward A., Bulargina, Tamara V., Severin, Eugene S.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate Ribose - metabolism; ADP-ribosylation; Aldehydes - metabolism; Aldehydes - pharmacology; Animals; Dithiothreitol - pharmacology; DTT, dithiothreitol; GA3P, glyceraldehyde-3-phosphate; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; Glyceraldehyde 3-Phosphate - metabolism; Glyceraldehyde 3-Phosphate - pharmacology; Glyceraldehyde-3-phosphate; Glyceraldehyde-3-phosphate dehydrogenase; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; Kinetics; Muscles - enzymology; NAD - metabolism; Nitroprusside - pharmacology; Rabbits; Substrate Specificity
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(93)81526-6

Nitric oxide was recently demonstrated to stimulate ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Our studies on the effect of glyceraldehyde-3-phosphate (GA3P), the natural substrate of dehydrogenase activity of GAPDH, indicated GA3P to be another very potent activator of ADP-ribosylation of the enzyme. GA3P was able to activate ADP-ribosylation only in the presence of DTT. The action of GA3P was associated with inhibition of GAPDH dehydrogenase activity. K a for GA3P was at least 50-fold lower and maximal activation was somewhat higher than these values for other aldehydes that were also able to enhance GAPDH ADP-ribosylation in the presence of DTT. ADP-ribosylation was blocked by carboxamidomethylation of the essential cysteine SH-group. The bond between the prelabeled protein and ADP-ribose was resistant to hydrolysis with hydroxylamine and HgCl 2, suggesting that a lysine ε-amino group is the target for ADP-ribosylation.