New insights into oxidative and nitrosative stress: the revolution of antibubble biomachineries

Abstract

Pierre A. Denis

Oxidative stress and, to a lesser degree, nitrosative stress are common to every disease. Nowadays, oxidative stress is detected by an abnormal amount of reactive oxygen species (ROS), mainly superoxide (O2 •- ). Reactive nitrogen species (RNS) from nitrosative stress derive all from the action of nitric oxide (NO•) and peroxynitrite (ONOO- ). Even though the chemical reactions and the action of their products have been described for decades, the overall process lacks consistency and clarity, and our understanding of diseases inevitably suffers as a result. In biology, and more generally when we consider a millimetric or infinitesimal volume, gas distribution is always anisotropic. Usual modeling of oxygen diffusion using Fick’s law does not reflect reality, as it does not take nanobubble formation into account due to this anisotropy. If we note nO2 as the number of oxygen molecules found in an infinitesimal volume, with n being a natural integer, nO2 can be seen as n dioxygen molecules that have been separated, but it can also be interpreted as a bubble comprising n molecules. Therefore, it becomes possible to rethink the action of a number of enzymes, which are involved on species designated 2O2 by biochemists and biologists. NADPH oxidase seems able to fix a 2O2 nanobubble. Due to their multimeric organization, NO synthase (NOS) and superoxide dismutase (SOD) capture quantum bubbles, which would otherwise have resulted in foam. NO synthase has been identified for the first time as an ultrasensitive detector for PO2 . Antibubble biomachinery means any enzymatic system, which prevents phase grouping by its action. Previous enzymes are identified as archetypes of antibubble biomachineries. We propose to unify ROS and RNS under the wording ‘Foam Breakdown Products’ (FBP). This attempt to unify the nitro-oxidative stress might prove to be fruitful to explain the pathophysiology of many diseases.