Support for Free Radical Theory

Because of their extreme reactivity, the existence of free radicals in biological systems was generally not considered possible until Gerschman and associates (G3) hypothesized that oxygen poisoning and X-irradiation have a common basis of action. Here, they reported the homolytic dissociation of water by ionizing radiation. 

It was subsequently learned that oxygen-derived radicals are normally produced in living organisms by a wide variety of reactions, especially in mitochondria and the electron transport chains in the endoplasmic reticulum, where the addition of an electron to molecular water produces superoxide (02 ). 

Superoxide is also a product of various enzyme reactions catalyzed by the flavin oxidases (e.g., xanthine oxidase and monoamine oxidase). In addition, 07 is a product of the noncatalytic oxidation of oxyhemoglobin, of which about 3% is converted each day to methemoglobin. Moreover, 02 is readily formed in phagocytic cells (i.e., neutrophils and monocytes) during the respiratory burst. Furthermore, in addition to the Fenton reaction, the Haber-Weiss reaction results in the conversion of 02 to the potent HO via the following reactions (H3)  

Various reduced transition metal ions (e.g., Cu1+, Fe2+) also react with 02 to 

Although direct toxicity of NO- is very modest, it is significantly increased when NO- reacts with 02 to form peroxynitrite (ONOO ), a very strong oxidant. 

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