What Part of NO Don't You Understand? Some Answers to the Cardinal Questions in Nitric Oxide Biology

Nitric oxide (NO) regulates biological processes through signaling mechanisms that exploit its unique biochemical properties as a free radical. For the last several decades, the key aspects of the chemical properties of NO relevant to biological systems have been defined, but it has been a challenge to assign these to specific cellular processes. Nevertheless, it is now clear that the high affinity of NO for transition metal centers, particularly iron, and the rapid reaction of NO with oxygen-derived free radicals can explain many of its biological and pathological properties. Emerging studies also highlight a growing importance of the secondary metabolites of NO-dependent reactions in the post-translational modification of key metabolic and signaling proteins. In this minireview, we emphasize the current understanding of the biochemistry of NO and place it in a biological context.