Since its discovery as the endothelium-derived relaxing factor, nitric oxide (NO) has garnered immense interest for a molecule so chemically simple but so functionally diverse. The complexity of its effects is demonstrated in a broad range of physiological functions and anti-pathogenic effects on one end, and a host of diseases and dysfunctions on the other. The beneficial and detrimental nature of NO is a function of concentration: sub-nM amounts are crucial for proper physiological functions, while its overproduction (μM concentration) causes damaging effects. Researchers therefore strive to understand how NO is either generated or expended. The first half of this review summarizes the different biological pathways for the generation and transportation of NO, starting with the classic conversion of L-arginine (L-Arg) via nitric oxide synthases (NOS). Other mechanisms such as the nitrite reductase activities of various enzymes, anhydrase activities of myoglobin (Mb) and hemoglobin (Hb), as well as the S-nitroso (SNO) formation of these globins will also be presented. The second part of this review focuses on synthetic metal complexes that donate NO upon UV-visible light exposure and have pharmacological potential. These select synthetic complexes contain metal centers such as iron (Fe), ruthenium (Ru), manganese (Mn), and chromium (Cr). This review highlights recent work that focuses on the natural (enzymes) and artificial (metal complexes) production of NO and their implications in human physiology and pharmacological potential.
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