Abstract

NO is an intermediate between molecular O2 and N2 that is generated enzymatically by nitric oxide synthase (NOS), of which there are three isoforms called NOS1, NOS2, and NOS3. In the presence of L-arginine and O2, all NOS enzymes catalyze the reaction that generates NO and L-citrulline. NO can also be generated by the reduction of nitrite (NO2−) that is facilitated by NO2− reductases. NO signaling can occur by binding to sGC, which generates the second messenger cGMP. NO can also regulate gene expression and protein function by nitrosylation. NO can be provided directly as NO gas, by NO donors, or by reduction of NO2−. NO signaling can be antagonized with compounds that block sGC or synthesis of NO by NOS. NO can regulate a vast array of physiological functions, including muscle contractility, metabolism, platelet aggregation, neuronal behavior, and immune responses. Dysfunction of NO production or signaling, as well as the NO metabolites, are implicated in many diseases.

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