Oxygen: boon yet bane—introducing oxygen toxicity and reactive species

Abstract This chapter explains how oxygen (O2) came to be present in the Earth's atmosphere (the evolution of photosynthesis), the changes in O2 levels that occurred during the Earth's history, and how they affected the behaviour of living organisms, including the 'Cambrian explosion', the fate of anaerobes, and the evolution of giant insects during the hyperoxia of the late Carboniferous period. The evolution of aerobes, aerobic respiration and its associated electron transport chains, and of eukaryotes is explored, and the nature of O2 toxicity to both anaerobes and aerobes (plants, reptiles, insects, bacteria, mammals) is presented, introducing the free-radical (superoxide) theory of O2 toxicity. How animals sense O2 and regulate its levels in a multicellular organism is discussed, including the hypoxia inducible factors (HIFs). The structure of mitochondria, their role in metabolism and energy production, and the mitochondrial permeability transition (MPT) are described. The endosymbiotic theory of the origin of mitochondria is critically reviewed, and how defects in mitochondrial DNA can cause disease. The molecular structure of O2 and of the radical (superoxide, hydroxyl) and non-radical (hydrogen peroxide, singlet O2) reactive species (RS) derived from it are explained, as are the sources of superoxide in vivo (cytochromes P450, mitochondria, haemoglobin, autoxidation reactions, and enzymes, including nitric oxide synthases). The mechanism of action of cytochromes P450 is presented. Xanthine dehydrogenase, xanthine oxidase and their inhibitors are discussed, as are the problems that can arise in cell culture due to hyperoxia and the abnormal environment that culture creates around cells.