A second redox group in monoamine oxidase: its role in catalysis and inhibition.

The currently accepted and well-documented radical mechanism for MAO catalysis has certain limitations. No flavin radical has ever been observed or trapped, the role of the essential thiol groups is not defined, and the mechanism provides no clue as to how binding of substrate can raise the redox potential of the MAO flavin by 0.5 V and accelerate the rate of reoxidation of the reduced enzyme. Recent work demonstrated that 4 electrons were needed for full reduction of the enzyme. It is hypothesized that another redox group, in addition to the flavin, is located in the active site in close proximity to the cofactor and that this group may be a disulphide. If a new mechanism involving a disulfide can be established, it could explain, by formation of thiol adducts, the time-dependent and slowly reversible action of some inhibitors.