Reduced Nucleotides, Thiols and O₂ in Cellular Redox Balance: A Biochemist's View

In the present review, which is aimed at researchers, teachers and students in life sciences, we try to show how the physicochemical properties of the elements and molecules define the concept of redox balance. Living organism are open systems traversed by fluxes of energy and matter. During catabolic oxidative metabolism, matter-mostly hydrogenated organic molecules-is oxidized and ultimately released as CO₂. Electrons are passed over to coupling molecules, such as NAD+ and FAD, whose reduced forms serve as electrons donors in anabolic reactions. Early photosynthetic activity led to the accumulation of O₂ and the transformation of the reduction to an oxidizing atmosphere, favoring the development of oxidative metabolism in living organisms. We focus on the specific properties of O₂ that provide the chemical energy for the combustion reactions occurring in living cells. We explain the concepts of redox potential and redox balance in complex systems such as living cells, we present the main redox couples involved in cellular redox balance and we discuss the chemical properties underlying their cellular roles and, in particular, their antioxidant properties in the defense against reactive oxygen species (ROS). Finally, we try to provide an integrative view emphasizing the interplay between metabolism, oxidative stress and metabolic compartmentation in mammalian cells.