Nitric oxide synthase physiological functions

NO, derived from L-arginine (L-Arg) by the enzyme nitric oxide synthase (NOS), is involved in the regulation of relevant physiological and pathophysiological functions. The mechanisms by which NO exerts its effects include activation of guanylate cyclase, formation of peroxynitrite, apoptosis, and COX regulation [96]. Apoptosis induction mediated by NO involves mitochondrial depolarization and is blocked by Bcl-2 overexpression [97]. 

ABSTRACT In mammals, nitric oxide (NO) is a reactive free radical involved in diverse physiological functions. NO and its redox-related forms NO+ and NO react with di(oxygen) and its derivatives, with metalloproteins and thiol-containing proteins. NO-mediated nitrosation of proteins represents an important cellular regulatory mechanism. Biosynthesis of NO is catalysed by nitric oxide synthase (NOS). Three isoenzymes representing distinct gene products have been identified the inducible NOS isoform, the constitutive neuronal and endothelial isoforms. Inducible and constitutive NOSs have the same structural features, but their activities differ in their dependence to calcium and the rate of NO produced. The principal NO-mediated functions in mammals are endothelium-dependent relaxation, neurotransmission and immune response. The role of NO in the antitumor immune response comprises both regulatory and effector functions at the intra- or inter-cellular level. The first function includes inhibition of lymphocyte proliferation or participation in different transduction pathways. The second fiinction includes pro- or anti-tumoral effects and NO-mediated cell toxicity or cell resistance to apoptosis. 

Nitric oxide synthase (NOS), the enzyme that generates nitric oxide (NO), is found in some neurons in the CNS. While NO plays a significant physiologic function in relaxation of vascular smooth muscle, a role for nitric oxide in synaptic transmission in the CNS has not been clearly established. Substance P is a neurotransmitter released from unmyelinated sensory neurons in the spinal cord involved in nociception. The answer is (D). 

As mentioned earlier, extensive literature is dedicated to the study of functions of NO synthases under physiological and pathophysiological conditions. Much attention has been drawn to the capacity of these enzymes to generate free radicals. The mechanism of nitric oxide production by NO synthases was widely discussed and are presented in Figure 22.3 [147]. 

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