Intervention of nitric oxide and its oxidized derivatives, particularly inmammals

Nitric oxide (NO) is a natural and stable free radical produced in soil and water by the bacteriological reduction of nitrites and nitrates and in ani mals by the enzyme oxidation of L-arginine. NO is biosynthesised by finely regulated enzymatic systems called NO-synthases and readily diffuses throug h tissues. It reacts rapidly with hemoproteins and iron-sulphur centers to form nitrosylated compounds. It oxidises more slowly to form nitrogen oxide s that nitrosate thiols into thionitrite. NO is transported in these variou s forms and released spontaneously or through yet unclear mechanisms into m ost cells; it also regulates oxygen consumption at the mitochondrial respir atory chain level through interaction with cytochrome oxidase. In the cardi ovascular system, NO lowers blood pressure by activating a hemoprotein, the guanylate cyclase present in muscle cells; through such interaction it act s also as a neuromediator and neuromodulator in the nervous system. However , many of NO's roles result from rapid coupling to other radicals; for exam ple, it reacts with the superoxide anion (O-2(-)) to form oxoperoxinitrate (ONOO-, also known as peroxynitrite). This strong oxidant of metallic cente rs, thiols, and antioxidants is also able to convert tyrosine to 3-nitrotyr osine and to act upon tyrosine residues contained in proteins. The biologic al aspects of the roles of NO are presented with particular respect to the rapid interactions of NO with hemoproteins' iron and other radicals. Concur rently, NO oxidation enables nitrosation reactions primarily of thiols but ultimately of nucleic bases. The thionitrite function (R-S-NO) thus formed and the dimerisation and nitration of tyrosine residues are protein post-tr anslational modifications that are being investigated in animals.