It is now almost universally recognized that most drugs undergo a vari ety of metabolic changes before they are excreted in the urine, bile, or air.Since drugs have widely different structures, it is not surprising that virtu ally every enzyme in the body may be considered as a drug-metabolizing enzyme. Indeed many drugs are specifically designed to resemble substances normally synthesized and catabolized in the bo dy and thus are metabolized by specific enzymes, which synthesize and catabolize substances such as cat echolamines, indoles, nucleic acids, amino acids, steroids, and fats. Most drugs, however, either are metabolized slowly by these spe cifi c enzymes or have no endogenous counterpart and thus are metabolized by nonspecific enzymes.In recent years, many investigators have focused their attention on the metabolism of drugs by a group of nonspecific enzymes in liver endoplasmic reticulum. The versatility of these enzymes is unique in biochemistry for they catalyze such widely diverse reactions as the ox idation of alkanes and aromat ic compounds, the epoxidation of alkenes, polycyclic hydrocarbons, and halogenated benzenes, the dealkylation of the s econdary and ter tiary amines, the conversion of amines to N-oxide, hydroxylamine, and nitroso derivatives, the oxidative cle avage of ethers and organic th iophosphate es ters, and the conversion of phosphothionates to their phosphate derivatives.In addition, thes e enzymes may catalyze the reduction of azo-compounds and nitro-compounds to primary aromatic amines and possibly the reductive cleavage of halogenated alkanes, such as carbon tetrachloride, to free radi cals (1-4).Since the oxidative reactions in the hepatic endoplasmic reticulum re quire both NADPH (or NADH) and oxygen, they are frequently called mixed-function oxidases, according to the nomenclature of Mason (5), or 1 Abbreviations used in this chapter are; DPEA; 2,4-dichloro-6-phenylphenoxy ethylamine; ESR; electron spin resonance; FAD; flavin adenine dinucleotide; Lilly 18947: 2,4-dichloro-6-phenylphenoxyethyl diethylamine ; MEOS: microsomal ethanol oxidizing system; NADP; nicotinamide adenine dinucleotide phosphate; NADPD: deuteriated nicotinamide adenine dinucleotide phosphate; NADPH; re duced nicotinamide adenine dinucleotide phosphate. 57 6528 Annu. Rev. Pharmacol. 1972.12:57-84. Downloaded from www.annualreviews.org by Indiana University -Purdue University Indianapolis -IUPUI on 10/02/12. For personal use only. Quick links to online content Further ANNUAL REVIEWS
