ABSTRACT
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Nitric oxide (NO) is a free radical, originally described as the endothelial relaxation factor, which is now considered as an intercellular messenger in physiological processes, such as vasodilation and regulation of blood flow, neurotransmission, plaquetary aggregation, and inmunological response, as well as an intracellular regulator of mitochondrial respiration. NO is synthesized from L-arginine, NADPH, and O2, by the isoenzymes of the NO synthases (NOS) family. Three isoforms have been cloned and characterized: nNOS (NOS1, neuronal NOS, originally identified as a constitutive form in neuronal tissue), iNOS (NOS2, inducible NOS, originally identified as a form inducible by cytokines in macrophages and hepatocytes), and eNOS (NOS3, endothelial NOS, originally identified as a constitutive form in vascular endothelial cells) (1, 2). A large series of cellular enzymatic activities is affected by NO concentrations in the range of the physiological levels. Considering the diffusion properties of NO, which equals a few cell diameters (3), it is difficult to set the limits between intracellular and
intercellular NO effects. Guanilate cyclase and cytochrome oxidase, in both cases with NO binding to an iron of the enzyme active center, are two metabolically important enzymes that are physiologically regulated by NO. In the first case, enzyme activation affords the mechanism for intercellular communication, and in the second case, the respiratory inhibition by NO generated intracellularly or in a neighbor cell appear as equally likely. The recognition of a NO synthase (NOS) localized in the mitochondria (mitochondrial NOS [mtNOS]) prompted the concept of NO-mediated intraorganellar regulation of mitochondrial function.
