Monoamine oxidases biotransformation reactions

It has been shown that 3 is biotransformed in a reaction catalysed by monoamine oxidase B to species that cause the selective degeneration of nigrostriatal neurons, giving rise to a Parkinsonian syndrome in man and other primates. Studies of this process have shown that the pyridinium salts 4 and 5 are involved, and that 4 undergoes spontaneous disproportionation to 5 and 3 5 is the putative ultimate neurotoxin. More recent studies have shown that 4 undergoes a spontaneous reaction in pH 7.4 buffer to give methylamine and a product identified as 6. 

Of the Phase I reactions, oxidative biotransformations are by far the most common. These reactions are carried out by several oxidative enzyme systems, the most predominant of which is the CYP superfamily of enzymes. Additional oxidative enzymes include FMO, xanthine oxidase, aldehyde oxidase, alcohol and aldehyde dehydrogenases monoamine oxidases, and various peroxidases. Determining the enzyme(s) employed to biotransform any particular substrate will depend on the substrates chemical and physical characteristics as well as functional substituents. This chapter does not describe in detail the mechanism of these various enzymes however, it does illustrate the product(s) (i.e., metabolites) produced by each reaction. 

Oxidative biotransformations, which constitutes the major portion of Phase I reactions, can be catalyzed by either cytochrome P450s (CYP450) or nonmicrosomal enzymes such as flavin-containing monooxygenases (FMOs), monoamine oxidase (MAOs), alcohol dehydrogenase, and aldehyde dehydrogenase. As listed in Table 5.1,... 

Oxidations are the most common biotransformation reactions that occur with most drugs. There are several classes of enzymes that carry out these reactions cytochrome P450s, flavin monooxygenases, monoamine oxidases, xanthine oxidase, aldehyde oxidases, aldehyde dehydrogenases, and peroxidases. Typical reactions and substrate substructures for each of these classes of enzymes will be described. 

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