Monooxygenase enzymes cytochrome

In the endoplasmic reticulum of eukaryotic cells, the oxidation of the terminal carbon of a normal fatty acid—a process termed ch-oxidation—can lead to the synthesis of small amounts of dicarboxylic acids (Figure 24.27). Cytochrome P-450, a monooxygenase enzyme that requires NADPH as a coenzyme and uses O, as a substrate, places a hydroxyl group at the terminal carbon. Subsequent oxidation to a carboxyl group produces a dicarboxylic acid. Either end can form an ester linkage to CoA and be subjected to /3-oxidation, producing a... 

Much work has demonstrated the presence of complex multienzyme monooxygenase systems within the endoplasmic reticulum of several mammalian species (for Reviews 1, 2, 3). These monooxygenase systems are responsible for the oxidative metabolism of many exogenous and endogenous substances, and the unusual non-specificity of these monooxygenase enzymes allows the metabolism of compounds with diverse chemical structures. Early work demonstrated that the terminal microsomal oxidase involved in xenobio-tic biotransformation was a hemoprotein, which has been subsequently named cytochrome P-450. 

Parathion is one of a class of phosphorothionate triesters widely used as insecticides. These compounds exert their toxic effects in insects and mammals by inhibiting the enzyme acetylcholinesterase. The phosphorothionates, in general, are relatively poor inhibitors of acetylcholinesterase but are converted by the cytochrome P-450-containing monooxygenase enzyme systems in insects and mammals to the corresponding phosphate triesters that are potent inhibitors of this enzyme. 

Parathion is also metabolized to diethyl phosphorothioic acid and -nitrophenol in a reaction requiring a cytochrome P-4Jg-containing monooxygenase enzyme system (, 4). Studies with H. 0 have indicated that water in addition to molecular oxygen and NADPH is required in this reaction ( ). Diethyl phosphate and -nitro-phenol can also be formed from parathion in a monooxygenase-catalyzed reaction (6). 

The flavin monooxygenases (FMOs) are a family of five enzymes (FMO 1-5) that operate in a manner analogous to the cytochrome P450 enzymes in that they oxidize the drug compound in an effort to increase its elimination. Though they possess broad substrate specificity, in general they do not play a major role in the metabolism of drugs but appear to be more involved in the metabolism of environmental chemicals and toxins. 

The rates of metabolism are also impaired in vitamin deficiency states (especially vitamin A, vitamin B, C and E). Starvation in mice leads to decrease in the rates of metabolism of certain drugs like pethidine, acetanilide, hexobarbitone etc. Ethanol increases the hepatic content of monooxygenase enzymes and cytochrome P450 on chronic ingestion. 

Foster BC, Sockovie ER, Bellefeuille NC, et al. Effect of St. John s wort on cytochrome P-450 and flavin monooxygenase enzymes and on P-glycoprotein. Can J Infect Dis 2001 12(suppl B) 132P. 

Monooxygenase Enzyme system (such as cytochrome P450) involved in the oxidation of xenobiotics. 

Another class of heme proteins containing iron protoporphyrin as the active center includes enzymes such as cytochrome P-450 and horseradish peroxidase (HRP). The former is a monooxygenase enzyme (MW 50,000) that catalyzes hydroxylation reaction of substrates such as drugs, steroids and carcinogens ... 

Cytochrome P450 enzymes are important in pharmaceutical research and development, because of their roles in drug metabolism.129 They are a ubiquitous class of haem enzymes, which act as monooxygenases in a wide variety of biological reactions. 

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