Mammalian flavin-containing monooxygenases

Published on July 8, 2010 Updated on September 30, 2015   34 min

A selection of talks on Metabolism & Nutrition

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Hello, and welcome to this presentation on mammalian flavin-containing monooxygenases, which we'll abbreviate as FMOs. The FMOs represent an enzyme family that's an important component of the body's armamentarium of oxidative drug metabolizing enzymes. I am Allen Rettie. And I will be your guide for this topic through the next 40 minutes.
Today's lecture will be divided into six main sections dealing with the structure, mechanism, enzyme multiplicity, gene regulation, and substrate specificity of the mammalian FMOs. We will also devote time to discussing experimental methods that permit the differentiation of FMO catalysis from that of the cytochrome P450s, both of which are present in the microsomal fraction of the cell. The presentation will conclude with suggestions for future research but begin with some historical background and an overview of the enzyme's general characteristics.
In the mid-1960s and early '70s, Dr. Dan Ziegler's group at the University of Texas at Austin provided the first evidence for a second NADPH and oxygen dependent monooxygenases system, located in the endoplasmic reticulum of the cell. The first such enzyme system was already known as cytochrome P450, an enzyme recognized to be a heme containing protein. Ziegler's group showed that hog liver microsome possess tertiary immune N oxygenase activity towards substrates such as N,N dimethylaniline. The resulting N oxide metabolite was uncharacteristic of cytochrome P450, which typically N, D alkylates tertiary amines. Subsequent purification of this new enzyme revealed that it lacked heme but contained a flavin cofactor. Consequently, the enzyme was named flavin-containing monooxygenases and assigned a new enzyme classification number 1, 14, 13, 8.