Development of human liver UDP-glucuronosyltransferases.
The development of multiple UDPGT activities towards eight substrates has been studied in fetal term and adult post-mortem (less than 5 h after death) liver samples. Most fetal and term liver activities were less than 14% of adult values, except that towards 5-hydroxytryptamine which was present in fetal and term liver at adult levels. The majority of UDPGT activities develop to adult levels within 10-20 weeks postnatally, and even premature (30 weeks) which survive for up to 10 weeks will develop these enzyme activities. Immunoblot analysis of human liver microsomes and cDNA cloning of human UDPGT shows the existence of the family of isoenzymes in man, and it is important to determine the developmental pattern of individual drug glucuronidating enzymes in liver. Immunoblot analysis of developing liver shows the presence of two major UDPGT polypeptides in fetal liver, whereas more than five are observed in adult liver. The investigation of substrate specificity of individual UDPGTs by expression of cloned genes in COS-7 cells and the use of antibodies will facilitate the identification of enzymes present in perinatal liver.
Burchell
B
B
Department of Biochemistry, University, Dundee, UK.
Coughtrie
M
M
Jackson
M
M
Harding
D
D
Fournel-Gigleux
S
S
Leakey
J
J
Hume
R
R
D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D014453:Glucuronosyltransferase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000254:growth & development*; D008862:Microsomes, Liver / Q000201:enzymology
D007527:Isoenzymes; D014453:Glucuronosyltransferase