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Comparison of glucuronidating activity of two human cDNAs, UDPGTh2 and UDPGTH2

Title
Comparison of glucuronidating activity of two human cDNAs, UDPGTh2 and UDPGTH2
Authors
Kim S.S.Owens I.S.Sheen Y.Y.
Ewha Authors
신윤용
SCOPUS Author ID
신윤용scopus
Issue Date
1997
Journal Title
Archives of Pharmacal Research
ISSN
0253-6269JCR Link
Citation
Archives of Pharmacal Research vol. 20, no. 5, pp. 454 - 458
Indexed
SCIE; SCOPUS; KCI scopus
Document Type
Review
Abstract
Two human liver UDP-glucuronosyltransferase cDNA clones, HLUG25 and UDPGTh2 were previously shown to encode isozymes active in the glucuronidation of hyodeoxycholic acid (HDCA) and certain estrogen derivatives (e.g., estriol and 3,4-catechol estrogens), respectively. In this study we have found that the UDPGTh2-encoded isoform (UDPGTh2) and HLUG25-encoded isoform (UDPGTh1) have parallel aglycone specificities. When expressed in COS 1 cells, each isoform metabolized three types of dihydroxy- or trihydroxy-substituted ring structures, including the 3,4-catechol estrogen (4-hydroxyestrone), estriol, 17-epiestriol, and HDCA, but the UDPGTh2 isozyme was 100-fold more efficient than UDPGTh1. UDPGTh1 and UDPGTh2 were 86% identical overall (76 differences out of 528 amino acids), including 55 differences in the first 300 amino acids of the amino terminus, a domain which conferred the substrate specificity. The data indicated that a high level of conservation in the amino terminus was not required for the preservation of substrate selectivity. Analysis of glucuronidation activity encoded by UDPGTh1/UDPGTh2 chimeric cDNA constructed at their common restriction sites, Sac I (codon 297), Nco I (codon 385), and Hha I (codon 469), showed that nine amino acids between residues 385 and 469 were important for catalytic efficiency, suggesting that this region represented a domain which was critical for the catalysis but distinct from that responsible for aglycone selection. These data indicate that UDPGTh2 is a primary isoform responsible for the detoxification of the bile salt intermediate as well as the active estrogen intermediates.
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약학대학 > 약학과 > Journal papers
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