The Mechanism (Reaction Pathway) of the MAOs

While MAO-A and MAO-B are isomers of the same enzyme structure, their functions are not as similar as one would think. Figure 1 shows an outline for the deamination mechanism that is catalyzed by MAO enzymes. Figure 2 shows the mechanism pathway used by MAO-B. Unfortunately, the pathway for MAO-A is still unknown. Organic chemistry fiends will not have any problem understanding the pathways. For the rest of the population, it is not crucial to know the steps but the products and by-products are implicated in certain neurological diseases like Parkinsons.

Figure 1 The first step involves the oxidation of the amine substrate and the reduction of FAD to FADH. Then the intermediate imine is hydrolyzed, and an aldehyde, an amine and FADH2 are formed.

In the second step, the FADH2 is oxidized back to FAD, and molecular oxygen is reduced to H2O2. Notice that the hydrogen peroxide (H2O2) is of concern because of the possibility of its subsequent oxidation into free radicals. This model was proposed by P.Dostert et. al in Italy.

Figure 2 This figure shows a more detailed picture of the mechanism of MAO-B, and also shows how hydrogen peroxide is oxidized to make free radicals. Hydrogen peroxide is normally removed by glutathione peroxidase, but whenever iron is associated with neuromelanin, it will donate an electron to the hydrogen peroxide, which will then divide into two hydroxyl radicals (-OH). These are extremely toxic to brain tissue. The purpose of MAO-inhibitors is to block the formation of hydrogen peroxide so that these radicals cannot be made. The model above was proposed by M.B.H. Youdim and P. Riederer at the University of Wurzburg, Germany.

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References