Nonmicrosomal enzymes

Hydrolysis, reduction, and other conjugation reactions catalyzed by nonmicrosomal enzymes... 

Oxidative biotransformations, which constitutes the major portion of Phase I reactions, can be catalyzed by either cytochrome P450s (CYP450) or nonmicrosomal enzymes such as flavin-containing monooxygenases (FMOs), monoamine oxidase (MAOs), alcohol dehydrogenase, and aldehyde dehydrogenase. As listed in Table 5.1,... 

Inhibitors for nonmicrosomal enzymes are also known disulfiram, for example, inhibits alcohol and aldehyde dehydrogenase, carbidopa inhibits dopa decarboxylase, allopurinol inhibits xanthine oxidase, phenelzine inhibits monoamine oxidase. 

Alcohols and aldehydes are metabolized by liver dehydrogenases that are nonmicrosomal and by nonspecific liver enzymes that are important in the catabolism of endogenous compounds. Ethanol is a special example of a compound whose metabolism is clinically relevant in that ethanol may interact with prescribed pharmaceuticals either metabol-ically or pharmacodynamically. Ethanol is metabolized first to acetaldehyde by alcohol dehydrogenase and then to acetic acid by aldehyde dehydrogenase, as shown in Scheme 11.29. These enzymes also play an important role in the metabolism of other... 

Other enzymes involved in phase I reactions are hydrolases (e.g., esterases and amidases) and the nonmicrosomal oxidases (e.g., monoamine oxidase and alcohol and aldehyde dehydrogenase). 

Besides the monooxygenases discussed above, a number of other oxidoreductases can oxidize xenobiotics. These enzymes are mostly but not exclusively nonmicrosomal, being present in the cytosol or mitochondria of the liver and extrahepatic tissues. The list includes alcohol dehydrogenases, aldehyde dehydrogenases, dihydrodiol dehydrogenases, haemoglobin, monoamine oxidases, xanthine oxidase and aldehyde oxidase. Some of these enzyme systems are discussed below. 

Disulfides (e.g., disulfiram), sulfoxides (e g., dimethylsulfoxide), N-oxides, double bonds such as those in progestational steroids, and dehydroxylation of aromatic and aliphatic hydroxyl derivatives are examples of reductions occurring in microsomal or nonmicrosomal (usually cytosol enzymes) fractions. 

Barbiturate, AIA, drugs, chloretone, benzpyrene Glucose-6-P-pentose-P Glucose-6-P dehydrogenase (nonmicrosomal), UDP-transglucuronidase (microsomal). Limiting enzymes for ascorbate synthesis ... 

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