The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyltransferase isoenzymes in rat and human liver microsomes.
Two anti-rat UDP-glucuronosyltransferase (UDPGT) antibody preparations, exhibiting different specificity of recognition of UDPGT isoenzymes on immunoblot analysis, were used to investigate the molecular basis of the perinatal inadequacy of glucuronidation in rats and humans. Immunoblot analysis of microsomes from developing rat liver demonstrated that the deficiency in bilirubin and testosterone glucuronidation in the fetus was due to the absence of the UDPGT isoenzyme proteins responsible for these conjugations. In contrast, phenol UDPGT enzyme activity and protein was detectable in significant amounts in fetal rat liver (greater than 30% of adult levels). In human liver, only one major immunoreactive polypeptide was observed in fetal microsomes. The remaining UDPGTs present in adult human liver developed postnatally, in parallel with the appearance of enzyme activities. Therefore, there was a correlation between the development of enzyme activity and enzyme protein. The possible consequences of developmental inadequacy of conjugation reactions for the fetus is discussed.
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D005260:Female; D005333:Fetus / Q000201:enzymology; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000254:growth & development*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D014453:Glucuronosyltransferase