NO-SYNTHASE AND NITRITE-REDUCTASE COMPONENTS OF NITRIC-OXIDE CYCLE

On the basis of our own experimental data and analysis of data from th e literature the existence of nitric oxide cycle in mammals is substan tiated. Two components underlie the nitric oxide cycle: 1) the reactio n catalyzed by NO-synthases (constitutive, inducible, and endothelial- NOS-I, -II, and -III); and 2) the nitrite-reductase reactions catalyze d by electron-donor systems with the participation of NADH, NADPH, fla voproteins, and heme-containing proteins. In mammalian cells NO is enz ymatically formed from terminal guanidine nitrogen of L-arginine by a family of at least three distinct NOS isoenzymes, As a result of nonen zymatic/enzymatic NO oxidation, NO2- and NO3- ions are formed: L-Arg - -> NO --> NO2-/NO3-. The reduction of NO2- ions to NO occurs via the n itrite-reductase reaction: NO2- + e(-) --> NO. The reduction of NO2- i ons to NO is realized by electron-donor systems with the participation of NADH, NADPH, flavoproteins, and cytochrome oxidase in mitochondria and by NADH, NADPH, flavoproteins, and cytochrome P-450 in endoplasmi c reticulum. In erythrocytes the reduction of NO2- ions to NO is catal yzed by electron-donor systems with participation of NADH, NADPH, flav oproteins, and deoxy-hemoglobin. The role of ascorbic acid and reduced glutathione should be noted among low-molecular-weight compounds. Thu s, the presence of the nitric oxide cycle provides the cyclic transfor mation as follows: L-arginine --> NO --> NO2-/NO3radical anion --> NO.