Harpers

Biologic Oxidation 11Peter A. Mayes, PhD, DSc, & Kathleen M. Botham, PhD, DScBIOMEDICAL IMPORTANCEChemically, oxidation is defined as the removal of electronsand reduction as the gain of electrons. Thus, oxidationis always accompanied by reduction of an electronacceptor. This principle of oxidation-reductionapplies equally to biochemical systems and is an importantconcept underlying understanding of the nature ofbiologic oxidation. Note that many biologic oxidationscan take place without the participation of molecularoxygen, eg, dehydrogenations. The life of higher animalsis absolutely dependent upon a supply of oxygenfor respiration, the process by which cells derive energyin the form of ATP from the controlled reaction of hydrogenwith oxygen to form water. In addition, molecularoxygen is incorporated into a variety of substratesby enzymes designated as oxygenases; many drugs, pollutants,and chemical carcinogens (xenobiotics) are metabolizedby enzymes of this class, known as the cytochromeP450 system. Administration of oxygen canbe lifesaving in the treatment of patients with respiratoryor circulatory failure.FREE ENERGY CHANGES CANBE EXPRESSED IN TERMSOF REDOX POTENTIALIn reactions involving oxidation and reduction, the freeenergy change is proportionate to the tendency of reactantsto donate or accept electrons. Thus, in addition toexpressing free energy change in terms of ∆G 0′ (Chapter10), it is possible, in an analogous manner, to express itnumerically as an oxidation-reduction or redox potential(E′ 0 ). The redox potential of a system (E 0 ) isusually compared with the potential of the hydrogenelectrode (0.0 volts at pH 0.0). However, for biologicsystems, the redox potential (E′ 0 )is normally expressedat pH 7.0, at which pH the electrode potential of thehydrogen electrode is −0.42 volts. The redox potentialsof some redox systems of special interest in mammalianbiochemistry are shown in Table 11–1. The relative positionsof redox systems in the table allows prediction ofthe direction of flow of electrons from one redox coupleto another.Enzymes involved in oxidation and reduction arecalled oxidoreductases and are classified into four86groups: oxidases, dehydrogenases, hydroperoxidases,and oxygenases.OXIDASES USE OXYGEN AS AHYDROGEN ACCEPTOROxidases catalyze the removal of hydrogen from a substrateusing oxygen as a hydrogen acceptor.* They formwater or hydrogen peroxide as a reaction product (Figure11–1).Some Oxidases Contain CopperCytochrome oxidase is a hemoprotein widely distributedin many tissues, having the typical heme prostheticgroup present in myoglobin, hemoglobin, andother cytochromes (Chapter 6). It is the terminal componentof the chain of respiratory carriers found in mitochondriaand transfers electrons resulting from theoxidation of substrate molecules by dehydrogenases totheir final acceptor, oxygen. The enzyme is poisoned bycarbon monoxide, cyanide, and hydrogen sulfide. It hasalso been termed cytochrome a 3 . It is now known thatcytochromes a and a 3 are combined in a single protein,and the complex is known as cytochrome aa 3 . It containstwo molecules of heme, each having one Fe atomthat oscillates between Fe 3+ and Fe 2+ during oxidationand reduction. Furthermore, two atoms of Cu are present,each associated with a heme unit.Other Oxidases Are FlavoproteinsFlavoprotein enzymes contain flavin mononucleotide(FMN) or flavin adenine dinucleotide (FAD) as prostheticgroups. FMN and FAD are formed in the bodyfrom the vitamin riboflavin (Chapter 45). FMN andFAD are usually tightly—but not covalently—bound totheir respective apoenzyme proteins. Metalloflavoproteinscontain one or more metals as essential cofactors.Examples of flavoprotein enzymes include L-aminoacid oxidase, an FMN-linked enzyme found in kidneywith general specificity for the oxidative deamination of* The term “oxidase” is sometimes used collectively to denote allenzymes that catalyze reactions involving molecular oxygen.