FAD-containing monooxygenase

Sabourin, PJ. and Hodgson, E. (1984) Characterization of the purified microsomal FAD-containing monooxygenase from mouse and pig liver. Chemico-Biological Interactions, 51, 125—139. 

The FAD-containing monooxygenase catalyzes oxidation of nucleophilic nitrogen and sulfur atoms in a diverse array of organic compounds. The enzyme... 

Beaty NB, Ballou DP. The reductive half-reaction of liver microsomal FAD-containing monooxygenase. J Biol Chem 1981 256(9) 4611-4618. 

The endoplasmic reticulum is composed of a convoluted network of channels and so has a large surface area. Apart from cytochromes P-450, the endoplasmic reticulum has many enzymes and functions, besides the metabolism of foreign compounds. These include the synthesis of proteins and triglycerides and other aspects of lipid metabolism and fatty acid metabolism. Specific enzymes present on the endoplasmic reticulum include cholesterol esterase, azo reductase, glucuronosyl transferase, NADPH cytochromes P-450 reductase and NADH cytochrome b5 reductase and cytochrome b5. A FAD-containing monooxygenase is also found in the endoplasmic reticulum, and this is discussed later in this chapter. 

Poulsen LL, Ziegler DM. The liver microsomal FAD-containing monooxygenase. Spectral characterization and kinetic studies. J. Biol. Chem. 1979 254 6449-6455. 

Sahourin PJ, Dahl AR. Distribution of the FAD-containing monooxygenase in respiratory tract tissues. Annual Report LMF-114. In Medinsky MA, Muggenhurg BA, eds. National Technical Information Service. Springfield, VA, 1985 156. 

Levi, P.E. and Hodgson, E., Stereospecificity in the oxidation of phorate and phorate sulfoxide by purified FAD-containing monooxygenase and cytochrome P-450 isozymes, Xenobiotica,... 

A microsomal enzyme system catalyses -dealkylation with oxidative removal of the alkyl group to yield the corresponding aldehyde, as with TV-dealky lation (figure 4,16). However, as there are certain differences from the TV-dealkylation reaction it has been suggested that another enzyme system, such as the microsomal FAD-containing monooxygenase system may be involved. 

Others such as pig liver microsomal FAD-containing monooxygenase have to be isolated from tissue with very low yields141 or like hydrocarbon monooxygenase from Pseudomonas oleovorans 12 131 require several protein components and cofactors, substantially limiting the use of these enzymes for the production of oxidized sulfur compounds. 

The (S)-(-)-sulfoxide is predominantly produced (82 % S, 18 % R) from p-tolyl ethyl sulfide when cyclohexanone monooxygenase from Acinetobacter sp. NCIB 9871191 was used, whereas the the FAD-containing monooxygenase from hog liver micro-somes oxidizes p-tolyl ethyl sulfide to yield the (R)-(+)-sulfoxide enantiomer as the major product (95 % R, 5 % S) 15). 

Enzymatically, //-oxidation can be catalysed by cytochrome P450 and/or by the FAD-containing monooxygenases, depending on substrates and conditions. From a chemical point of view, the oxidation of nitrogen atoms in organic compoimds can be summarized as follows ... 

Imidazoleacetate and i.-lysine monooxygenases from pseudomonads were obtained in crystalline form. Both enzymes were established to contain FAD probably as a sole cofactor. Available evidence indicates that the reaction catalyzed by these enzymes involves the reduction of FAD, the monooxygenation of substrate, and the reoxidation of reduced FAD. The mechanism of activating molecular oxygen by these FAD-containing monooxygenases is discussed. 

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