NITRIC-OXIDE - A SIGNAL FOR ADP-RIBOSYLATION OF PROTEINS

Nitric oxide (NO), a highly reactive gas, is now established as a majo r messenger molecule regulating blood vessel dilation. immune function s and serving as a neurotransmitter in brain and peripheral nervous sy stem. NO can also act as a tumoricidal and bactericidal molecule. The effect of NO to dilate blood vessels is largely explained by stimulati on of soluble guanylate cyclase (a heme-iron containing protein) leadi ng to formation of cGMP and protein phosphorylation. This is considere d to be the main physiological signaling mechanism of NO. NO also bind s to non-heme iron-containing-proteins and this has been considered as a pathophysiological or cytotoxic action of NO. Furthermore, NO, more correctly nitrosonium (NO+) which can be formed by the removal of one electron, reacts with protein SH-groups to cause the S-nitrosylation of proteins. We have recently established a link between NO and the S- nitrosylation and mono-ADP-ribosylation of the enzyme glyceraldehyde 3 -mopophosphate dehydrogenase, which adds a further protein modificatio n mechanism for NO action. This links the formation of the second mess enger molecule NO to post-translational protein modification and adds a new dimension to NO in the communication of intracellular signals.