Nature Of The 4a-flavinhydroperoxide Of Microsomal Flavin-containing Monooxygenase (flavoprotein, Hydroperoxide, Oxygen, Oxygenation, Flavinhydroxide).

Abstract

Microsomal flavin-containing monooxygenase catalyzes the oxygenation of many different nucleophilic and electrophilic compounds. The mechanism for this reaction has been shown to include two enzyme-bound 4a-substituted flavin species; the 4a-flavin hydroperoxide serves as the oxygen donating species and the 4a-flavin hydroxide is the flavin product after oxygen transfer to substrate. The main thrust of this work has been to study the chemistry of these two species utilizing stopped flow spectrophotometry as well as steady state kinetics and other, spectroscopic techniques. The results from these studies indicate the flavin hydroperoxide performs oxygenations in a manner consistent with other hydroperoxides. However, the rates of oxygenation of both nucleophilic and electrophilic compounds are much faster with the enzyme bound flavin hydroperoxide than are the rates of oxygenation utilizing a model flavin hydroperoxide, free in solution. The manner which the enzyme enhances the rate of oxygen transfer is discussed. This work also shows that release of water from the flavin hydroxide and release of hydrogen peroxide from the flavin hydroperoxide are effected by different conditions which may offer information concerning the environment around the active site of the enzyme. The study of this enzyme is useful in two regards. First, this enzyme represents a class of enzymes, the flavin monooxygenases, that have been studied extensively. Properties of microsomal flavin-containing monooxygenase have made it a particularly useful enzyme to clarify the chemistry of the oxygen transfer reaction which is an unsolved problem for this class of flavoproteins. Second, the enzyme is active in the metabolism of a wide variety of xenobiotics. The study of the metabolism of these compounds is of interest to pharmacologists and toxicologists.