Linked Life Data

14744946

Source:http://linkedlifedata.com/resource/pubmed/id/14744946

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-27
pubmed:abstractText
Carvedilol ((+/-)-1-carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol) is metabolized primarily into glucuronide conjugates. In the present study, we identified the human UDP-glucuronosyltransferase (UGT) isoforms involved in the glucuronidation of carvedilol by thin-layer chromatography using microsomes from human liver or insect cells expressing recombinant UGT isoforms. We observed two forms of carvedilol glucuronides, namely G1 and G2, in hepatic microsomes. The glucuronidation of carvedilol was catalyzed by at least three recombinant UGT isoforms: UGT1A1, UGT2B4, and UGT2B7. UGT2B4 formed both G1 and G2, whereas UGT1A1 and UGT2B7 were responsible for the formation of glucuronide G2 and G1, respectively. The enzyme kinetics for carvedilol glucuronidation by UGT1A1, UGT2B4, and UGT2B7 in addition to human liver microsomes were examined by Lineweaver-Burk analysis. The values of Km and Vmax for human liver microsomes were 26.6 microM and 106 pmol/min/mg protein for G1, and 46.0 microM and 44.5 pmol/min/mg protein for G2, respectively. The Km values for UGT1A1, UGT2B4, and UGT2B7 for G1 and G2 (22.1-55.1 microM) were comparable to those of the liver microsomes, whereas the Vmax values were in the range of 3.33 to 7.88 pmol/min/mg protein. The Km and Vmax/Km values for UGT2B4 and UGT2B7 for G1 were similar, whereas UGT2B4 had lower Km and higher Vmax/Km values for G2 compared with those of UGT1A1. These results suggest that G1 formation is catalyzed by UGT2B4 and UGT2B7, whereas G2 is formed by UGT2B4 and UGT1A1. These three hepatic UGT isoforms may have important roles in carvedilol metabolism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0090-9556
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-9
pubmed:dateRevised
2007-4-28
pubmed:meshHeading
pubmed-meshheading:14744946-Adolescent, pubmed-meshheading:14744946-Adrenergic beta-Antagonists, pubmed-meshheading:14744946-Adult, pubmed-meshheading:14744946-Aged, pubmed-meshheading:14744946-Animals, pubmed-meshheading:14744946-Carbazoles, pubmed-meshheading:14744946-Child, pubmed-meshheading:14744946-Child, Preschool, pubmed-meshheading:14744946-Chromatography, Thin Layer, pubmed-meshheading:14744946-Female, pubmed-meshheading:14744946-Glucuronides, pubmed-meshheading:14744946-Glucuronosyltransferase, pubmed-meshheading:14744946-Humans, pubmed-meshheading:14744946-Insects, pubmed-meshheading:14744946-Isoenzymes, pubmed-meshheading:14744946-Kinetics, pubmed-meshheading:14744946-Male, pubmed-meshheading:14744946-Microsomes, pubmed-meshheading:14744946-Middle Aged, pubmed-meshheading:14744946-Propanolamines
pubmed:year
2004
pubmed:articleTitle
Involvement of human hepatic UGT1A1, UGT2B4, and UGT2B7 in the glucuronidation of carvedilol.
pubmed:affiliation
Division of Environmental Chemistry, National Institute of Health Sciences, Tokyo 158-8501, Japan. a-ohno@nihs.go.jp
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, Non-U.S. Gov't