The expression of UDP-glucuronosyltransferases of the UGT1 family in human liver and kidney and in response to drugs.
The expression of human UDP-glucuronosyltransferase (UGT) 1 gene family in the liver and kidney was examined using specific enzyme activity, antibodies and DNA probes for each of the four family members. Phenol UGT HP1 was expressed at a similar, relatively low, abundance in each liver and kidney whereas phenol UGT HP4 was more highly expressed in the kidney. Bilirubin UGTs (HP2 and HP3) were not detectable in the kidney and HP3 was the major isoform in the liver. The UGT activities towards certain specific substrates correlated well with the respective mRNA levels in the tissues. Bilirubin UGT HP3 was induced 2-3-fold in the livers from patients treated with phenytoin and phenobarbital. Storage of a human liver in University of Wisconsin solution which contains dexamethasone and insulin caused a large accumulation of all the UGT mRNAs, but these were not quantitatively translated into expressed UGT activities. The implications of these results are discussed.
Sutherland
L
L
Department of Biochemical Medicine, Ninewells Hospital and Medical School, University of Dundee, U.K.
Ebner
T
T
Burchell
B
B
D000368:Aged; D001663:Bilirubin / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008875:Middle Aged; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D013379:Substrate Specificity
D005965:Glucuronates; D007527:Isoenzymes; D012333:RNA, Messenger; D010672:Phenytoin; D014453:Glucuronosyltransferase; D001663:Bilirubin; D010634:Phenobarbital