Premium
How are Biogenic Amines Metabolized by Monoamine Oxidases? (Eur. J. Org. Chem. 36/2012)
Author(s) -
Vianello Robert,
Repič Matej,
Mavri Janez
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201290099
Subject(s) - chemistry , flavin group , deprotonation , hydride , cofactor , protonation , substrate (aquarium) , stereochemistry , monoamine oxidase , adduct , flavin adenine dinucleotide , medicinal chemistry , enzyme , organic chemistry , hydrogen , ion , oceanography , geology
The cover picture shows a scheme of the rate‐limiting first step of dopamine metabolism catalyzed by the flavoenzyme monoamine oxidase. The enzyme uses the flavin adenine dinucleotide (FAD) cofactor to perform its catalytic activity through the process initiated by an α‐CH abstraction from the substrate. Over the years, there has been a heated debate whether the hydrogen is transferred as a proton, a radical or a hydride. Our work presents substantial evidence in favour of the hydride transfer mechanism. This reaction produces a covalent adduct between the hydrided anionic FADH – and the cationic substrate, to be followed by the deprotonation of the free amino group in the second step, releasing final products, fully reduced flavin, FADH 2 and the neutral trans ‐imine. Details of the most feasible hydride mechanism are discussed in the article by R. Vianello et al. on p. 7057 ff.