N CH2CH3 154
first is to the inactive S-oxide 152, while the second oxidation generates the active agent, but a stable, noncytotoxic amide 153 is the only product isolated (Scheme 16). These results imply that the cytotoxic agent is a reactive intermediate that can break down to 153. It has been postulated168 that the reactive intermediate is a sulfinic acid 154, which upon hydrolysis yields 153.
5.05.2.3 Monoamine Oxidase (MAO)
5.05.2.3.1 Occurrence, multiplicity, distribution, oxygen activation, and selectivity
MAO, like FMO, is an enzyme that relies on the redox properties of FAD for its oxidative machinery. The enzyme exists as two isoforms, MAO-A and MAO-B, that share a sequence homology of approximately 70%.169 They are found in the outer mitochondrial membrane, and are widely distributed in mammalian tissues. The isoforms differ in substrate selectivity170 and tissue distribution.171 MAO-A is located primarily in the placenta, gut, and liver, while MAO-B is predominant in the brain, liver, and platelets. In humans, MAO-B constitutes about 80% of the enzyme found in the liver.172 The primary function of both isoforms appears to be to catalyze the oxidative deamination of the arylalkylamino neurotransmitters, to form the corresponding aldehydes. MAO-A is selective for serotonin and norepinephrine, and is selectively inhibited173 by the mechanism-based inhibitor clorgyline (155). MAO-B is selective for b-phenethylamine and tryptamine, and is selectively inhibited173 by the mechanism-based inhibitors deprenyl (156) and pargyline (157). Recently, both MAO-A174and MAO-B175 were structurally characterized by x-ray crystallography.
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