Life and Death in an Oxygen Atmosphere

Everybody is talking about antioxidants. Newspapers, magaines and television report the beneficial effects of antioxidants, and the pharmaceutical industry is selling billions of dollars worth of these dietary supplements, but very few people really know what antioxidants are, why they exist and how they do what they do. Oxygen plays a central role in these reactions. People usually believe that oxygen is something good for our health and they are completely unaware of the numerous damaging and even lethal effects of oxygen. Oxygen provides us with the energy to carry out all the functions of our cells and organs. However, the oxygen metabolism was found to lead to reactive oxygen metabolites, some of which are radicals. ROMs play an important role in many normal biological as well as pathological processes. Radicals are highly reactive species and for many decades were considered of minor significance in biological systems. At present there is evidence for radical involvement in over 100 diseases. We no longer have to concern ourselves only with outside agents (bacteria, viruses, pollution) that affect our health, but also with damage caused by agents of normal oxygen metabolism. The following pathological processes will be discussed: Aging, amyotrophic lateral sclerosis, Alzheimer's disease, Atherosclerosis, Cancer, Lung disease, Multiple sclerosis, and Parkinson's disease. During the course of evolution, our bodies have developed defenses against ROMs. These defenses consist of the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), metal complexing proteins, uric acid, melatonin and small molecules taken up in our diet, the vitamins A, C and E. The basis of biology is chemistry. Once we understand the chemistry of ROMs we can better rationalize the pathology. Numerous diseases with diverse clinical symptoms can be understood at the most basic level by the concept of 'oxidative stress', which is a disturbance of the prooxidant/antioxidant balance of a system. The importance of balance has been recognized for centuries by Chinese philosophers (Yin-Yang) and was expressed by Paracelsus: everything is poison, it just depends on the dose. The thread of pro and con runs through most of radical biology and medicine. Our cells are carrying out a precarious balancing act. The concentrations of many chemicals in our bodies have to be strictly controlled. The antioxidants ascorbic acid (Vitamin C) and α-tocopherol (Vitamin E) are essential for life, but under certain conditions can have damaging (prooxidant) effects. During the course of this book I shall discuss numerous examples of pros and cons in reactive oxygen metabolite chemistry and pathology The reactive oxygen metabolites are damaging to our cells and the accumulated damage leads to aging, cancer and other degenerative diseases. Thus it appears that death is inherent with life and programmed already from the very beginning through the oxygen metabolism. This text is on an interdisciplinary subject, involving chemistry, biology and medicine. In order to understand biology and medicine we have to understand the underlying chemistry. An important part of this book is therefore devoted to the chemistry of oxygen and its metabolites (ROMs and radicals).