Variations in activity and inhibition with pH: the protonated amine is the substrate for monoamine oxidase,but uncharged inhibitors bind better |
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Authors: | T. Z. E. Jones D. Balsa M. Unzeta R. R. Ramsay |
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Affiliation: | (1) Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews, U.K.;(2) Department Bioquimica Biologia Molecular, Universitad Autonoma Barcelona, Barcelona, Spain |
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Abstract: | Summary It has been accepted that, as required mechanistically, the neutral form of the amine is the substrate for monoamine oxidase, despite the amine pK a of above 9.5. The pH dependence of the kinetic parameters for kynuramine oxidation by purified human MAO-A and for phenylethylamine oxidation by MAO-B in granulocytes at pH values from 5 to 10 was consistent with the protonated amine being used. Deprotonation of a group of pK a = 7.1 in MAO-B and pK a = 7.5 ± 0.1 (n = 4) in MAO-A was important for efficient catalysis. The Ki values for two oxazolidinone inhibitors of MAO-A gave opposite pH-dependence indicating that the uncharged form of each inhibitor bound better than the charged form. Decreased pH induced a blue shift in the spectral maximum of MAO-A indicative of a more hydrophobic environment around the flavin, and also influenced the redox properties of the flavin. |
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Keywords: | : Monoamine oxidase kinetics |
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