NITROGEN(II) OXIDE (NITRIC-OXIDE, NO) - ITS ORIGIN, FATE AND PHYSIOLOGICAL SIGNIFICANCE - A REVIEW

The nitrogen oxide (NO), a free radical molecule, plays a key role in the regulation of mammalian physiology and pathophysiology, e.g., in c ardiovascular, nervous or immune systems. This molecule is produced fr om guanidino moiety of amino acid L-arginine with N-G-hydroxy-L-argini ne as intermediate and L-citrulline as a co-product of this reaction. This conversion is catalyzed by an ezyme called NO-synthase. The NO-sy nthase belongs to the cytochrome P450 superfamily and four its isoenzy mes are known so far. Two (denoted NOS-I and III) are constitutive, ge nerate lower amounts (pmol) of NO and are regulated by Ca++/calmodulin system. The others (NOS-II and IV) are inducible, produce a larger qu antity of NO (nmol) and are regulated at a transcriptional level. The constitutive form is present, for example, in endothelial and neuronal cells whereas the inducible form is de novo synthesized as a conseque nce of certain stimuli (including cytokines) in macrophages, vascular smooth muscle cells and other cells. There are several target molecule s for NO depending on cells. The most frequent target is supposed to b e the soluble guanylate cyclase. However, superoxide anion is a very i mportant target for NO, too. The reaction between these two molecules leads to the production of peroxynitrite, the fate of which depends on environmental conditions. Therefore, the importance of this reaction is still debated. This review deals with the nature of NO, the mechani sms of its production, the role of intermediate N-G-hydroxy-L-arginine and summarizes the biology of superoxide anion with respect to its re action with NO. A review with 218 references.