REVIEW: NO-Synthase and Nitrite-Reductase Components of Nitric Oxide Cycle

V. P. Reutov^* and E. G. Sorokina

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, ul. Butlerova 5a, Moscow, 117865 Russia; fax: (095) 338-8500

^* To whom correspondence should be addressed.

Received July 17, 1997

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On the basis of our own experimental data and analysis of data from the literature the existence of nitric oxide cycle in mammals is substantiated. Two components underlie the nitric oxide cycle: 1) the reaction catalyzed by NO-synthases (constitutive, inducible, and endothelial--NOS-I, -II, and -III); and 2) the nitrite-reductase reactions catalyzed by electron-donor systems with the participation of NADH, NADPH, flavoproteins, and heme-containing proteins. In mammalian cells NO is enzymatically formed from terminal guanidine nitrogen of L-arginine by a family of at least three distinct NOS isoenzymes. As a result of nonenzymatic/enzymatic NO oxidation, NO₂^- and NO₃^- ions are formed: L-Arg --> NO --> NO₂^-/NO₃^-. The reduction of NO₂^- ions to NO occurs via the nitrite-reductasereaction: NO₂^- + e^- --> NO. The reduction of NO₂^- ions 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 endoplasmic reticulum. In erythrocytes the reduction of NO₂^- ions to NO is catalyzed by electron-donor systems with participation of NADH, NADPH, flavoproteins, and deoxy-hemoglobin. The role of ascorbic acid and reduced glutathione should be noted among low-molecular-weight compounds. Thus, the presence of the nitric oxide cycle provides the cyclic transformation as follows: L-arginine --> NO --> NO₂^-/NO₃^- --> NO.

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KEY WORDS: nitric oxide cycle, Hb--NO and Mb--NO-complexes, NO₂^- and NO₃^- ions, hypoxia

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