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  • Title: UDP-glucuronosyltransferase activity in human liver and colon.
    Author: Strassburg CP, Nguyen N, Manns MP, Tukey RH.
    Journal: Gastroenterology; 1999 Jan; 116(1):149-60. PubMed ID: 9869613.
    Abstract:
    BACKGROUND & AIMS: The contribution of glucuronidation toward human drug metabolism is carried out by the Super gene family of UDP-glucuronosyltransferases (UGTs). Regulation of the human UGT1A locus is tissue specific, resulting in the unique expression of multiple hepatic and extrahepatic gene products. Studies were undertaken to examine UGT1A expression in human hepatic and colonic tissues. METHODS: UGT1A messenger RNA, protein, catalytic activity, and substrate kinetics were studied in 5 samples of normal hepatic and sigmoid colon tissue using duplex reverse-transcription polymerase chain reaction (RT-PCR), enzymatic and Western blot analysis, and indirect immunofluorescence analysis. RESULTS: Specific patterns of UGT1A gene expression occur in the liver and colon, which were consistent with different banding patterns as detected by Western blot analysis using a UGT1A-specific antibody. However, microsomal UGT activities in colon were up to 96-fold lower for many phenolic substrates, a finding that was not concordant with RT-PCR and Western blot analysis. Interestingly, UGT activity toward tertiary amines and some steroid hormones was equal. CONCLUSIONS: Differences of glucuronidation activity between human liver and colon suggest that UGT1A activity may be regulated as a result of the relative presence of individual isoforms with differing catalytic activities or by tissue-specific modulators after gene expression.
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