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Nitric oxide preferentially stimulates auto‐ADP‐ribosylation of glyceraldehyde‐3‐phosphate dehydrogenase compared to alcohol or lactate dehydrogenase
Author(s) -
Dimmeler Stefanie,
Brüne Bernhard
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)81124-i
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , alcohol dehydrogenase , dehydrogenase , lactate dehydrogenase , nad+ kinase , chemistry , enzyme , biochemistry , nitric oxide , adp ribosylation , organic chemistry
Recently we demonstrated that the radical nitric oxide (NO) stimulates the auto‐ADP‐ribosylation of the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) resulting in enzyme inhibition. To further characterize this auto‐ADP‐ribosylation reaction we studied alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH) for comparison. Whereas auto‐ADP‐ribosylation of ADH was stimulated to a minor extent by the NO‐liberating agent 3‐morpholinosydnonimine (SIN‐1), LDH was unaffected. The susceptibility of dehydrogenases towards autoADP‐ribosylation correlated with the potency of NO to decrease enzyme activity. Again, GAPDH was much more sensitive compared to ADH, whereas LDH again was unaffected. Interestingly, the efficiency of the SH‐alkylating agent N ‐ethylmaleimide (NEM) to inhibit the enzymatic activity of the chosen dehydrogenases correlates with the sensitivity of dehydrogenases towards NO. These studies demonstrate the requirement of a reactive SH‐group besides the NAD + binding site as a prerequisite for NO‐stimulated auto‐ADP‐ribosylation reactions. Furthermore, we establish that under physiological conditions and among the dehydrognases tested, only GAPDH is a potential target for this post‐translational protein modification mechanism.