Ch3

The role of MAO-A and MAO-B in regulating the concentration of the amine neurotransmitters offered a strategy for treating pathologies that involve these critical biomolecules. Thus, drugs have been developed that are used to treat the symptoms of depression by inhibiting MAO-A MAO-B.177

or neurodegenerative diseases such as parkinsonism by inhibiting

5.05.2.3.2 Mechanism of monoamine oxidase oxygen activation and oxidation of substrate

Overall, the catalytic activity of MAO can be characterized as two half-reactions.171 In the first the amine substrate is oxidized, and the FAD cofactor is reduced to FADH2, while in the second the imine product is released, and the FADH2 cofactor is re-oxidized to FAD, generating peroxide in the process. The released imine chemically hydrolyzes to the corresponding aldehyde.

A mechanism involving a SET has generally been accepted178 (Figure 6a), although evidence for a HAT

mechanism exists (Figure 6b), and a polar nucleophilic mechanism has also been advanced

5.05.2.3.3 Oxidation of xenobiotic amines

The most well-documented case of a MAO-B-catalyzed oxidation of a nonbiogenic amine183 is the conversion of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (158) to N-methyl-4-phenyl-2,3-dihydropyridine (MPDP+)

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