title: Substrates but not inhibitors alter the redox potentials of monoamine oxidases.
abstract: The midpoint potentials for the reduction of the cysteinyl-flavin adenine dinucleotide (FAD) in monoamine oxidases (MAO) A and B in the absence and presence of ligands have been determined. Both MAO A and MAO B can be reduced chemically in two steps, the first generating a semiquinone spectrum and the second the spectrum of fully reduced FAD, each of which requires two electron equivalents. The midpoint potentials for the oxidized/semiquinone and semiquinone/reduced couples were -159+/-4 mV and -262+/-3 mV for MAO A and -167+/-4 mV and -275+/-3 mV for MAO B. After modification with a thiol reagent, direct reduction from the oxidized to fully reduced form was observed with no semiquinone and without change in the overall midpoint potential. In the presence of substrate, no semiquinone was formed, but the midpoint potential for full reduction of the flavin was positively shifted by up to 500 mV, depending on the substrate. This shift in potential could permit a more thermodynamically favorable transfer of electrons from the amine substrates to oxygen. In contrast, stable products and inhibitors did not cause a shift in potential and did not prevent the formation of semiquinone.
authors.affiliation: Department of Biochemistry and Biophysics, University of California San Francisco, 94143, USA.
authors.forename: S O
authors.initials: SO
authors.lastname: Sablin
authors.forename: R R
authors.initials: RR
authors.lastname: Ramsay
mesh_terms: D004220:Disulfides / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008099:Liver / Q000201:enzymology; D008956:Models, Chemical; D008995:Monoamine Oxidase / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry; D013439:Sulfhydryl Reagents / Q000494:pharmacology
chemical_list: D004220:Disulfides; D008024:Ligands; D011725:Pyridines; D011809:Quinones; D013439:Sulfhydryl Reagents; C007542:4,4'-dipyridyl disulfide; D008995:Monoamine Oxidase