Breathing new life into nitric oxide signaling: A brief overview of the interplay between oxygen and nitric oxide

●Oxygen is a major determinant of the rates of nitric oxide synthesis and metabolism.●Under biological conditions nitric oxide only reacts with metals and other free radicals.●Oxygen determines the half-life, concentration, and diffusional distance of nitric oxide.●Proteins respond to nitric oxide in a concentration and time-dependent manner.●Oxygen and the redox environment will greatly influence signaling responses to nitric oxide.

Nitric oxide (
• NO, nitrogen monoxide) is one of the most unique biological signaling molecules associated with a multitude of physiologic and pathological conditions. In order to fully appreciate its numerous roles, it is essential to understand its basic biochemical properties. Most signaling effector molecules such as steroids or proteins have a significant life-span and function through classical receptor–ligand interactions.
• NO, however, is a short-lived free-radical gas that only reacts with two types of molecules under biological conditions; metals and other free radicals. These simple interactions can lead to a myriad of complex intermediates which in turn have their own phenotypic effects. For these reasons, responses to
• NO often appear to be random or contradictory when outcomes are compared across various experimental settings. This article will serve as a brief overview of the chemical, biological, and microenvironmental factors that dictate
• NO signaling with an emphasis on
• NO metabolism. The prominent role that oxygen (dioxygen, O2) plays in
• NO metabolism and how it influences the biological effects of
• NO will be highlighted. This information and these concepts are intended to help students and investigators think about the interpretation of data from experiments where biological effects of
• NO are being elucidated.

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