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RESEARCH PRODUCT

Nitric Oxide: Biological Synthesis and Functions

subject

description

The pluripotent gaseous messenger molecule nitric oxide (NO) controls vital functions such as neurotransmission or vascular tone (via activation of soluble guanylyl cyclase), gene transcription, mRNA translation (via iron-responsive elements), and post-translational modifications of proteins (via ADP-ribosylation). In higher concentrations, NO is capable of destroying parasites and tumor cells by inhibiting iron-containing enzymes or directly interacting with the DNA of these cells. In view of this multitude of functions of NO, it is important to understand the mechanisms by which cells accomplish and regulate the production of this molecule. In mammals, three isozymes of NO synthase (NOS; L-arginine, NADPH:oxygen oxidoreductases, nitric oxide forming; EC 1.14.13.39) have been identified. These isoforms are referred to as neuronal “n”NOS (or NOS I), inducible “i”NOS (or NOS II), and endothelial “e”NOS (or NOS III). In pathophysiology, massive amounts of NO produced by hyperactive nNOS or highly expressed iNOS can contribute to processes such as neurodegeneration, inflammation, and tissue damage. This chapter will describe principles of NO biosynthesis, regulatory mechanisms controlling the production of this molecule, and the large array of (physiologic and pathophysiologic) functions that Mother Nature has assigned to this small messenger molecule.