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dc.contributor.advisorBrodbelt, Jennifer S.en
dc.creatorRobotham, Scott Allenen
dc.date.accessioned2013-02-28T21:13:59Zen
dc.date.issued2012-12en
dc.date.submittedDecember 2012en
dc.identifier.urihttp://hdl.handle.net/2152/19676en
dc.descriptiontexten
dc.description.abstractBased on reactions with two flavanones, three flavonols, and five flavones the regioselectivities of twelve human UDP-glucuronosyltransferase (UGT) isozymes were elucidated. The various flavonoid glucuronides were differentiated based on LC-MS/MS fragmentation patterns of [Co(II)(flavonoid – H)(4,7-diphenyl-1,10-phenanthroline)2]+ complexes generated upon post-column complexation. Glucuronide distributions were evaluated to allow a systematic assessment of the regioselectivity of each isozyme. The various UGT enzymes, including eight UGT1A and four UGT2B, displayed a remarkable range of selectivities, both in terms of the positions of glucuronidation and relative reactivity with flavanones, flavonols and flavones. The UGT1A enzyme selectivities are affected by the presence of a hydroxyl group at the 3, 6, 4’, or 3’ positions as well as by the presence of a methoxy at the 3’ position. The UGT2B enzymes show poor to no reactivity with the flavonols or flavones. This result implies that the greater planarity of the flavonols and flavones compared to structure of flavanones inhibits interaction with the UGT2 enzymes. For baicalein and scutellarein, three of the UGT1A isozymes (1A8, 1A9, and 1A10) resulted in the formation of 6-O glucuronides, enabling the fragmentation rules for the metal complexation/MS/MS strategy to be expanded.en
dc.format.mimetypeapplication/pdfen
dc.language.isoen_USen
dc.subjectHuman UDP-glucuronosyltransferaseen
dc.subjectFlavonoiden
dc.subjectRegioselectivityen
dc.subjectMass spectrometryen
dc.subjectMetal complexationen
dc.subjectGlucuronidationen
dc.titleEvaluation of the regioselectivity of human UDP-glucuronosyltransferase isozymes with three common sub-classes of flavonoids via metal complexation and tandem mass spectrometryen
dc.date.updated2013-02-28T21:14:00Zen
dc.contributor.committeeMemberHolcombe, James Aen
dc.description.departmentChemistryen
thesis.degree.departmentChemistryen
thesis.degree.disciplineChemistryen
thesis.degree.grantorThe University of Texas at Austinen
thesis.degree.levelMastersen
thesis.degree.nameMaster of Artsen


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