title: The human UDP glucuronosyltransferase, UGT1A10, glucuronidates mycophenolic acid.
abstract: The cDNA encoding the UDP glucuronosyltransferase, UGT1A10, has been cloned from human colon. The deduced amino acid sequence of the cDNA is 90% similar in sequence to that of a previously characterized form, UGT1A9 (Hlug P4), and contains a signal peptide and carboxyl-terminal hydrophobic domain characteristic of all UDP glucuronosyltransferases isolated to date. The enzyme synthesized in UGT1A10 cDNA-transfected COS-7 cells has a relative molecular mass of 56 kDa and is very active in the glucuronidation of mycophenolic acid (apparent Km of 34 microM and Vmax of 0.6 nmoles/min/mg protein). Other UGTs (UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 2B10 and 2B11) synthesized in COS cells had relatively little activity towards mycophenolic acid, suggesting that UGT1A10 may have a significant role in the elimination of this antineoplastic and immunosuppressive agent in vivo.
authors.affiliation: Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park.
authors.forename: B
authors.initials: B
authors.lastname: Mojarrabi
authors.forename: P I
authors.initials: PI
authors.lastname: Mackenzie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000302:isolation & purification; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009173:Mycophenolic Acid / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D014453:Glucuronosyltransferase; D009173:Mycophenolic Acid