Monoamine oxidase mechanism-based inhibition

Liquid chromatography/ultraviolet detection Monoamine oxidase Mechanism-based inhibition Metabolic intermediate complex Molybdenum-containing oxidase Multi parameter optimization... 

B. Mechanism-Based Inhibition of Monoamine Oxidase Unsaturated Alkylamines. .. 340... 

Other acetylenic derivatives inhibit other enzyme systems by mechanism-based inhibition, for example 3-hydroxydecanoyl thioester dehydratase, lactate dehydrogenase, monoamine oxidase and cytochrome P450i d4,23,24 inhibition of the last two systems by acetylenic compounds will be discussed later in this chapter. 

Figure 8.23. Mechanism-Based (Suicide) Inhibition. Monoamine oxidase, an enzyme important for neurotransmitter synthesis, requires the cofactor FAD (flavin adenine dinucleotide). AA -Dimethylpropargylamine inhibits monoamine oxidase by covalently modifying the flavin prosthetic group only after the inhibitor is first oxidized. The N-5 flavin adduct is stabilized by the addition of a proton.

Suicide inhibitors, or mechanism-based inhibitors are modified substrates that provide the most specific means to modify an enzyme active site. The inhibitor binds to the enzyme as a substrate and is initially processed by the normal catalytic mechanism. The mechanism of catalysis then generates a chemically reactive intermediate that inactivates the enzyme through covalent modification. The fact that the enzyme participates in its own irreversible inhibition strongly suggests that the covalently modified group on the enzyme is catalytically vital. One example of such an inhibitor is N,N-dimethylpropargylamine. A flavin prosthetic group of monoamine oxidase... 

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