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dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorWimalasena, D. Shyamalien_US
dc.contributor.authorWimalasena, Kandategeen_US
dc.identifierNS 39423en_US
dc.identifier.citationThe Journal of biological chemistry. 2004 Apr 9; 279(15): 15298-304.en_US
dc.descriptionClick on the DOI link below to access the article.en_US
dc.description.abstractThe nature of coupling between the uptake and dopamine-beta-monooxygenase (DbetaM) catalyzed hydroxylation of dopamine (DA) was studied in bovine chromaffin granule ghosts. Initial rate and transient kinetics of DA uptake and conversion were determined under a variety of conditions. The uptake kinetics of DA, norepinephrine (NE), and epinephrine demonstrate that DA is a better substrate than NE and epinephrine under optimal uptake conditions. The transient kinetics of DA accumulation and NE production under both optimal uptake and uptake and conversion conditions were zero-order with no detectable lag or burst periods. The mathematical analyses of the data show that a normal sequential uptake followed by the conversion process could not explain the observed kinetics, under any condition. On the other hand, all experimental data are in agreement with a mechanism in which DA is efficiently channeled from the vesicular monoamine transporter to membranous DbetaM for hydroxylation, prior to the release into the bulk medium of the ghost interior. The slow accumulation of DA under optimal conversion conditions appears to be caused by the slow leakage of DA from the channeling pathway to the ghost interior. Because DbetaM activity in intact granules is equally distributed between soluble and membranous forms of DbetaM, if an efficient channeling mechanism is operative in vivo, soluble DbetaM may not have access to the substrate, making the catalytic activity of soluble DbetaM physiologically insignificant, which is consistent with the increasing experimental evidence that membranous DbetaM may be the physiologically functional form.en_US
dc.description.sponsorshipNINDS NIH HHSen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.relation.ispartofseriesThe Journal of biological chemistryen_US
dc.relation.ispartofseriesJ. Biol. Chem.en_US
dc.subjectResearch Support, U.S. Gov't, P.H.S.en_US
dc.subject.meshBiogenic Monoamines/chemistryen_US
dc.subject.meshBiological Transporten_US
dc.subject.meshChromaffin Cells/metabolismen_US
dc.subject.meshChromatography, High Pressure Liquiden_US
dc.subject.meshDopamine beta-Hydroxylase/chemistryen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshModels, Biologicalen_US
dc.subject.meshModels, Chemicalen_US
dc.subject.meshModels, Theoreticalen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshTime Factorsen_US
dc.titleKinetic evidence for channeling of dopamine between monoamine transporter and membranous dopamine-beta-monooxygenase in chromaffin granule ghostsen_US
dc.coverage.spacialUnited Statesen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 2004 by The American Society for Biochemistry and Molecular Biology, Incen_US

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