Purification and properties of two rat liver phenobarbital-inducible UDP-glucuronosyltransferases that catalyze the glucuronidation of opioids.
Glucuronidation of xenobiotics and endobiotics is catalyzed by a group of intrinsic membrane proteins of the endoplasmic reticulum of cells: the UDP-glucuronosyltransferases. Two isoforms with glucuronidation activity toward opioids have been purified and characterized from liver microsomes obtained from phenobarbital-treated Wistar rats. The proteins have been identified as the gene products of UGT2B1 and UGT1.1r. The purified proteins exhibited the same apparent KM values for morphine glucuronidation (2-3 mM). However, the purified UGT1.1r enzyme exhibited glucuronidation activity toward buprenorphine and bilirubin with high efficiency, but the UGT2B1 protein did not react with these compounds. Both purified enzymes glucuronidated chloramphenicol, 4-hydroxybiphenyl, chrysin, and ibuprofen. Flunitrazepam photoaffinity labeling was demonstrated for both enzymes, and naloxone, the opioid antagonist, antagonized the photoaffinity labeling reactions.
Coffman
B L
BL
Department of Pharmacology, University of Iowa, Iowa City 52242, USA.
Rios
G R
GR
Tephly
T R
TR
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000378:metabolism; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000302:isolation & purification* / Q000378:metabolism*; D007527:Isoenzymes / Q000302:isolation & purification* / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D008969:Molecular Sequence Data; D009020:Morphine / Q000378:metabolism; D010634:Phenobarbital; D051381:Rats; D017208:Rats, Wistar
D000701:Analgesics, Opioid; D007527:Isoenzymes; D009020:Morphine; D014453:Glucuronosyltransferase; D010634:Phenobarbital