title: Identification of bilirubin UDP-GTs in the human alimentary tract in accordance with the gut as a putative metabolic organ.
abstract: The initial identification of traditionally hepatic enzymes expressed in the gut has led to the hypothesis that the gut may function as a metabolic organ. The UDP glucuronosyltransferases (UDP-GTs) play an important role as phase II metabolizing enzymes. Previously members of this family have been identified in the gut by non-isoform specific immunoreactivity, and a small amount of bilirubin glucuronosyltransferase activity was detected in the colon. Recent reports of gut transplantation to reverse the metabolic defect in Gunn rats raised further interest in the expression and distribution of human bilirubin (UDP-GTs (HUG Br 1 and HUG Br 2) in the human alimentary tract. The availability of molecular genetic probes for HUG Br 1 and HUG Br 2 permits the screening of the alimentary tract for the presence of isoform specific message. RNA samples extracted from pinch biopsy specimens of buccal mucosa, esophagus, stomach body, antrum, duodenum, and colon were analyzed for expression of HUG Br 1 and HUG Br 2. HUG Br 1 hybridization was detected in duodenum > colon, whereas HUG Br2 hybridization was detected in duodenum > esophagus > colon. Immunoreactivity data confirmed the presence of HUG Br 1 protein at low levels in the duodenum, whereas the less abundant HUG Br 2 protein was below the limits of detection of isoform specific anti-peptide antibodies. Bilirubin specific reactivity was demonstrated in duodenal samples but not antrum samples, consistent with the molecular genetic data. The presence of functional bilirubin UDP-GT isoforms in human alimentary tract supports the notion that the gut may function as a metabolic organ and may have diagnostic and therapeutic implications for disorders of bilirubin metabolism.
authors.affiliation: Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor 48109, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: McDonnell
authors.forename: E
authors.initials: E
authors.lastname: Hitomi
authors.forename: F K
authors.initials: FK
authors.lastname: Askari
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001706:Biopsy; D015153:Blotting, Western; D002460:Cell Line; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004064:Digestive System / Q000201:enzymology*; D005260:Female; D014453:Glucuronosyltransferase / Q000032:analysis* / Q000096:biosynthesis*; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D009061:Mouth Mucosa / Q000201:enzymology; D009928:Organ Specificity; D051381:Rats; D011911:Rats, Gunn; D011994:Recombinant Proteins / Q000032:analysis / Q000096:biosynthesis; D012016:Reference Values; D014162:Transfection
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D011994:Recombinant Proteins; C019787:bilirubin glucuronoside glucuronosyltransferase; D014453:Glucuronosyltransferase