The kinetic mechanisms of monoamine oxidases A and B

Abstract

Introduction Questions raised by the existence of two forms of monoamine oxidase (MAO) with overlapping distribution, substrate specificities and inhibitor sensitivities has fascinated pharmacologists and biochemists for several decades (for recent reviews, see [l-31). It is now known that the flavin sites are identical [4] and, indeed, that the two enzymes show 71% sequence homology [2]. The differences must lie in the substrate binding site, but they affect not just the substrate specificity but also the kinetics of the oxidation process. Early steady-state kinetic studies using a wide variety of substrates and both purified and crude (membrane bound) preparations of the enzyme obtained double reciprocal plots with the parallelline pattern indicating a ping-pong (double displacement) mechanism (e.g. [S-71) in which the enzyme forms only binary complexes with the substrates and products. However, as demonstrated for other flavoprotein oxidases [8], parallel lines can be obtained in double reciprocal plots even when a ternary complex exists, if some of the terms in the rate equation are very small. The rate equations for the two mechanisms are given below: