Antioxidant Systems

Vitamins C and E, as well as ubiquinones (Fig. 3) and derivatives of the nonmetallic element selenium, together with sulfur-containing proteins, all participate in an elaborate antioxidant system. This system protects us against many of the adverse effects of reduced oxygen compounds such as hydrogen peroxide (H2O2), superoxide (O2−), and hydroxyl (OH) radicals. The system is quite complex and not fully understood. However, ascorbic acid, which can itself form free radicals readily, appears to be a key player. Water-soluble and present in a high concentration, its role seems to be to keep many cellular components reduced. The tocopherols (vitamin E), in their various isomeric forms, scavenge free radicals formed from oxidation of unsaturated fatty acids within cell membranes. Vitamin E is especially effective in removing organic peroxide radicals. Supplementation with dietary vitamin E is being tested for prevention or amelioration of a variety of diseases of aging including atherosclerosis and Parkinson’s and Alzheimer’s diseases. The resulting tocopherol radicals are rereduced by ascorbate in the aqueous phase. Ascorbate can also donate electrons to ubiquinone radicals present in the membranes of the mitochondria. It is within the mitochondria that many damaging radicals are thought to arise as side products of the reduction of O2 that occurs there.

In addition to its antioxidant role, ascorbic acid functions to keep various metallic ions in catalytic centers in their reduced forms. For example, some oxygenases require iron or copper in their Fe2+ or Cu+ states of oxidation. If these protein-bound ions are accidentally left in a more oxidized state they may need to be reduced by ascorbate ions. While this is a protectant role, there are some enzymes for which ascorbate has become a cosubstrate. An example is dopamine β-hydroxylase, which converts dopamine to the neurotransmitter noradrenaline. The enzyme contains copper which cycles between Cu+ and Cu2+, as it incorporates one atom of oxygen from O2 into its substrate. Ascorbate supplies the electrons for reduction of the second atom of the O2 to H2O. A recent report describes another distinct function for ascorbate ion. It apparently acts as a basic catalytic group for proton abstraction from a water molecule during the action of a glycosyltransferase enzyme, becoming part of the active site of that enzyme.