Mirroring Human Monoamine Oxidases A And B: Similar Structures With Opposite Mechanisms Of C-H Bond Cleavage
FASEB JOURNAL(2013)
摘要
Due to their importance in age‐related degenerative diseases, mammalian monoamine oxidases A and B (MAO A and B) have been the object of extensive studies. The mechanistic description for the MAO‐catalyzed oxidation of amines is controversial resulting in three different proposed mechanism including a hydride ion abstraction (Fitzpatrick, 2010), a proton abstraction involving an intermediate covalent adduct on the flavin (Miller and Edmondson, 1999), or a proton abstraction following a radical pair formation (Lu et al., 2002). It is largely assumed that MAO A and MAO B follow the same mechanistic pathway. Comparison of the influence of para substituents on reaction rates by steady‐state and stopped‐flow kinetic analysis has been used to determine electronic effects of various benzylamine analogs. Human MAO A exhibits a positive ρ (+1.4) characteristic of a H + abstraction while human MAO B exhibits a negative ρ (−0.9) characteristic of a Habstraction. These results suggest the two enzymes follow differing catalytic mechanisms thus demonstrating the assumption they follow identical mechanisms is not correct. Supported by grant GM‐29344 from the NIH.
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关键词
human monoamine
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