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dc.contributor.authorPretorius, Anél
dc.contributor.authorOgunrombi, Modupe O.
dc.contributor.authorTerre'Blanche, Gisella
dc.contributor.authorBergh, Jacobus J.
dc.contributor.authorPetzer, Jacobus P.
dc.date.accessioned2009-12-17T12:22:28Z
dc.date.available2009-12-17T12:22:28Z
dc.date.issued2008
dc.identifier.citationPretorius, A. et al. 2008. Deuterium isotope effects for the oxidation of 1-methyl-3phenyl-3pyrrolinyl analogues by monoamine oxidase B. Bioorganic & medicinal chemistry, 16(19):8813-8817. [https://doi.org/10.1016/j.bmc.2008.09.001]en
dc.identifier.issn0968-0896 (Online)
dc.identifier.issn1464-3391
dc.identifier.urihttp://hdl.handle.net/10394/2682
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0968089608008225
dc.identifier.urihttps://doi.org/10.1016/j.bmc.2008.09.001
dc.description.abstractThe parkinsonian inducing agent, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is a cyclic tertiary allylamine exhibiting good monoamine oxidase B (MAO-B) substrate properties. MAO-B catalyzes the ring α-carbon 2-electron bioactivation of MPTP to yield the 1-methyl-4-phenyl-2,3-dihydropyridinium species (MPDP+). The corresponding 5-membered ring MPTP analogue, 1-methyl-3-phenyl-3-pyrroline, also undergoes MAO-B-catalyzed oxidation to give the 2-electron oxidation product, 1-methyl-3-phenylpyrrole. Here we report the kinetic deuterium isotope effects on Vmax and Vmax/Km for the steady-state oxidation of 1-methyl-3-phenyl-3-pyrroline and 1-methyl-3-(4-fluorophenyl)-3-pyrroline by baboon liver MAO-B, using the corresponding pyrroline-2,2,4,5,5-d5 analogues as the deuterated substrates. The apparent isotope effects for the two substrates were 4.29 and 3.98 on Vmax, while the isotope effects on Vmax/Km were found to be 5.71 and 3.37, respectively. The values reported for the oxidation of MPTP by bovine liver MAO-B with MPTP-6,6-d2, as deuterated substrate, are D(Vmax) = 3.55; D(Vmax/Km) = 8.01. We conclude that the mechanism of the MAO-B-catalyzed oxidation of pyrrolinyl substrates is similar to that of the tetrahydropyridinyl substrates and that a carbon–hydrogen bond cleavage step is, at least partially, rate determining
dc.language.isoenen
dc.publisherElsevieren
dc.subjectMonoamine oxidase B
dc.subjectMPTP
dc.subject1-Methyl-3-phenyl-3-pyrroline
dc.subjectKinetic isotope effect
dc.titleDeuterium isotope effects for the oxidation of 1-methyl-3phenyl-3pyrrolinyl analogues by monoamine oxidase Ben
dc.typeArticleen
dc.contributor.researchID12264954 - Petzer, Anél
dc.contributor.researchID10727388 - Petzer, Jacobus Petrus
dc.contributor.researchID10057072 - Bergh, Jacobus Johannes
dc.contributor.researchID10206280 - Terre'Blanche, Gisella
dc.contributor.researchID12608351 - Ogunrombi, Modupe Olufunmilayo


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