Antioxidant defences synthesized in vivo

Abstract This chapter defines the term 'antioxidant', explains the different mechanisms of antioxidant action, and describes the antioxidants synthesized by living organisms: how they are made, how they work, and their importance in vivo. One defence is to control exposure to O2, as illustrated by stem cells and nitrogen fixation. Antioxidants described in detail include the superoxide dismutases (CuZnSOD, mitochondrial MnSOD, FeSOD, NiSOD, cambialistic SODs), how to measure their activity, and why superoxide is damaging (direct toxicity, H2O2, hydroxyl radical, and peroxynitrite formation). Glutathione, the enzymes that synthesize and degrade it (γ-glutamylcysteine synthetase, glutathione synthetase and γ-glutamyl transpeptidase), and those that use it (e.g. glutathione peroxidases, glutathione-S-transferases, glyoxalases), are described. Superoxide reductases, thioredoxins, peroxiredoxins, catalase, other peroxidases (especially ascorbate, cytochrome c, and horseradish peroxidases), trypanothione, mycothiol, bacillithiol, homoglutathione, haem oxygenases (HO-1 and HO-2), metallothioneins, albumin, sulphiredoxins, oestradiol, melatonin, ergothioneine, tryparedoxin, ovothiols, carnosine, homocarnosine, lipoic acid, mycosporine-glycine, urate, melanin, bilirubin, Mn2+ as a replacement for SOD and a constituent of some catalases, pyruvate, coenzyme Q, and trehalose are reviewed as putative antioxidants in vivo. The roles of peroxiredoxins, catalase, and glutathione peroxidases in removing H2O2, and how they co-operate with SODs, is discussed. Selenium, iron, and copper metabolism are presented in relation to antioxidant defence, and to deficiency and overload diseases such as Wilson disease and haemochromatosis. Regulation of body iron and copper stores is explained in relation to the need to prevent oxidative damage, including methods to detect the labile iron pool. The relation of gender to antioxidant defence is discussed.