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N ‐Nitrosomelatonin outcompetes S ‐Nitrosocysteine in inhibiting Glyceraldehyde 3‐Phosphate Dehydrogenase: first evidence that N ‐Nitrosomelatonin can modify protein function
Author(s) -
Kirsch Michael,
De Groot Herbert
Publication year - 2008
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2007.00517.x
Subject(s) - glyceraldehyde 3 phosphate dehydrogenase , cysteine , chemistry , dehydrogenase , enzyme , nitroxyl , biochemistry , glutathione , glyceraldehyde , photochemistry
Abstract: Low‐molecular‐weight S ‐nitrosothiols (RSNOs) are well known for their capability to transnitrosate cysteine residues of enzymes thereby altering their catalytic activity. It is unknown, however, whether N ‐nitrosomelatonin (NOMela) which is highly effective in transnitrosating low‐molecular‐weight thiols (RSHs) can also alter protein function. In the present study, we report on such a capability with glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) as a target enzyme. Reaction of NOMela with GAPDH resulted in an increase of RSNOs at the expense of RSHs. Somewhat surprisingly, NOMela was about 10‐fold more effective than S ‐nitrosocysteine in inhibiting GAPDH. Vitamin C and glutathione increased the NOMela‐dependent inhibition of the enzyme by accelerating the intermediacy of nitroxyl which is also highly effective in nitrosating RSHs. The occurrence of this intermediate during the NOMela–vitamin C reaction was verified by using Mn(III)‐tetrakis(1‐methyl‐4‐pyridyl)porphorin pentachloride as nitroxyl scavenger. The NOMela‐dependent inactivation of GAPDH was so effective that this reaction can be used to quantify NOMela with high sensitivity.