Biological origin of free radicals, and mechanisms of antioxidant protection

Abstract

Reduced intermediates of molecular oxygen, such as superoxide and hydrogen peroxide, are ubiquitous inorganic products of normal aerobic metabolism. Certain cells, such as phagocytes, have evolved to use superoxide and hydrogen peroxide for purposeful chemistry beneficial to the host, but most cells require antioxidant protection against excessive production of these intermediates. Superoxide and hydrogen peroxide are themselves poorly reactive in aqueous solution, and unable to directly damage DNA, lipids and proteins. Excessive generation, however, of superoxide and hydrogen peroxide invariably accompanies molecular damage. Substantial evidence suggests that conversion of these poorly reactive intermediates of oxygen to highly reactive forms requires the participation of transition metal ions, particularly iron. Iron ions react with hydrogen peroxide (Fenton chemistry) to generate hydroxyl radicals that can damage all organic molecules.