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Development of human liver UDP-glucuronosyltransferases
B Burchell1, M Coughtrie, M Jackson
1Department of Biochemistry, University, Dundee, UK.
Developmental Pharmacology and Therapeutics
|January 1, 1989
Summary
Most UDPGT activities in fetal liver are significantly lower than adult levels, except for 5-hydroxytryptamine. These crucial drug-metabolizing enzyme activities develop postnatally.
Area of Science:
- Pharmacology
- Developmental Biology
- Hepatology
Background:
- UDP-glucuronosyltransferases (UGTs) are critical enzymes for drug and xenobiotic metabolism.
- Understanding the developmental expression of UGTs is essential for predicting drug efficacy and toxicity in neonates and infants.
Purpose of the Study:
- To investigate the developmental patterns of multiple UDPGT activities in human fetal and adult liver.
- To identify specific UDPGT isoenzymes present in perinatal liver and their substrate specificities.
Main Methods:
- Assay of UDPGT activities towards eight different substrates in fetal and adult post-mortem liver samples.
- Immunoblot analysis of human liver microsomes to identify UDPGT polypeptides.
- cDNA cloning of human UDPGTs and expression in COS-7 cells to determine substrate specificity.
Main Results:
- Fetal and term liver UDPGT activities were generally less than 14% of adult levels, with 5-hydroxytryptamine being a notable exception.
- Two major UDPGT polypeptides were detected in fetal liver, compared to more than five in adult liver.
- Most UDPGT activities mature to adult levels within 10-20 weeks postnatally.
Conclusions:
- Significant developmental changes occur in human liver UDPGT activities, impacting drug metabolism in early life.
- The study highlights the importance of characterizing individual UDPGT isoenzymes and their developmental trajectories.
- Further investigation using cloned genes and antibodies is crucial for identifying perinatal UDPGT enzymes.