Related Experiment Video

Updated: Jun 5, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
08:59

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

The development of UDP-glucuronosyltransferases 1A1 and 1A6 in the pediatric liver

Shogo J Miyagi1, Abby C Collier

  • 1Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Mānoa, 651 Ilalo St., BSB 320, Honolulu, HI 96813, USA.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|January 27, 2011
PubMed

Insights

UDP-glucuronosyltransferases (UGTs) activity matures in pediatric livers, with UGT1A1 and UGT1A6 reaching peak activity at different ages. This enzyme maturation impacts drug and chemical clearance in children.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Pediatrics

Background:

  • UDP-glucuronosyltransferases (UGTs) are crucial enzymes for metabolizing and clearing drugs, chemicals, and endogenous compounds.
  • Understanding the developmental trajectory of UGTs in pediatric populations is essential for predicting drug efficacy and toxicity.

Purpose of the Study:

  • To investigate the developmental maturation of UDP-glucuronosyltransferase 1A1 (UGT1A1) and UDP-glucuronosyltransferase 1A6 (UGT1A6) in pediatric liver samples.
  • To assess the correlation between enzyme activity, protein expression, and age.
  • To predict normalized hepatic clearances using pharmacokinetic modeling.

Main Methods:

  • Analysis of 50 pediatric liver samples.
  • Enzyme activity assays (bilirubin, serotonin).
  • Western blot for protein expression.
  • Pharmacokinetic scaling using allometry and a physiologically based pharmacokinetic model (Simcyp).

Main Results:

  • UGT1A1 activity peaked at 3.8 months, while UGT1A6 activity matured at 14 months.
  • Enzyme activity was age-dependent, but protein expression was not.
  • Activities did not correlate with protein levels for either UGT1A1 or UGT1A6.
  • Pharmacokinetic models predicted normalized adult clearances for UGT1A1 and UGT1A6, with some model convergence differences.

Conclusions:

  • UGT1A1 and UGT1A6 exhibit independent developmental regulation, with activity maturing between 6 months and 1 year.
  • Delayed maturation of these UGT enzymes may influence the clearance of substances and contribute to chemical, drug, and environmental toxicity in children.
  • Hepatic clearance maturation may be influenced by other physiological factors beyond UGT development.

More Related Videos

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies09:51

Human Liver Spheroids from Peripheral Blood for Liver Disease Studies

Published on: January 27, 2023

Related Concept Videos

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
Phase II Reactions: Glucuronidation01:24

Phase II Reactions: Glucuronidation

Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
Jaundice01:25

Jaundice

Jaundice, or icterus, is the yellow discoloration of the skin, sclerae, and mucous membranes. It happens when plasma bilirubin levels rise above 2.5-3 mg/dL, leading to bilirubin deposition in tissue.Bilirubin is a byproduct of hemoglobin degradation. In macrophages, hemoglobin breaks down into globin and heme. Globin is converted into amino acids, while heme is turned into biliverdin by heme oxygenase, which is then reduced to unconjugated bilirubin by biliverdin reductase.Unconjugated...
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes: