The Mechanism of Action of Flavoprotein - Catalyzed Reactions

1983 is not only the 100th anniversary of the birth of Otto Warburg, but is also the 50th anniversary of the determination of the structure of the flavin chromophore by Kuhn and Wagner-Jauregg (1930) and the 50th anniversary of the isolation of the first flavoprotein, the Old Yellow Enzyme of brewers bottom yeast (Warburg and Christian 1933). In the intervening 50 years, some 200 different flavoproteins have been recognized, making this one of the largest single groups of related enzymes. These enzymes function in the catalysis of key steps in virtually every metabolic pathway in all life forms. They catalyze a variety of different types of chemical reaction in which the flavin is intimately involved. With a few exceptions, where the role of the flavin is not clear, e.g., glyoxylate carboligase (Cromartie and Walsh 1976) or oxynitrilase (Jorns 1980), flavoproteins carry out oxidationreduction reactions, where one substrate is oxidized and a second is reduced. For all these enzymes, each catalytic cycle consists of two distinct processes, the acceptance of redox equivalents from a reducing substrate and the transfer of these equivalents to an oxidized acceptor. Accordingly, catalysis is comprised of two separate halfreactions: (1) the reductive half-reaction where the flavin is reduced and (2) the oxidative half-reaction, where the reduced flavin is reoxidized. This feature is very convenient experimentally, since it is possible to study each half-reaction separately. In this way, it is generally possible to identify individual steps in each half-reaction, often with the determination of the absorption spectra of intermediates and the rate constants of their formation and decay. This information can then be combined and fitted to catalytic turnover data, sometimes even employing the spectral properties of the flavin itself to monitor enzyme catalytic turnover (Gibson et al. 1964).