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Developmental profile of mitochondrial glycine N-acyltransferase in human liver
Y Mawal1, K Paradis, I A Qureshi
1Department of Pediatrics, Hôpital Sainte-Justine, University of Montreal, Quebec, Canada.
Insights
Liver glycine N-acyltransferase (GAT) activity in children develops slowly, reaching adult levels by 18 months. This delayed GAT development may impact drug detoxification in early life.
Area of Science:
- Biochemistry
- Pediatric Medicine
- Pharmacology
Background:
- Glycine N-acyltransferase (GAT) is crucial for xenobiotic detoxification.
- Understanding the developmental profile of GAT is essential for assessing pediatric drug metabolism.
Purpose of the Study:
- To investigate the developmental trajectory of glycine N-acyltransferase (GAT) activity in pediatric livers.
- To compare GAT activity in children across various age groups with adult controls.
Main Methods:
- Liver samples from 13 children (4 hours to 11 years) and 3 adults (24-40 years) were analyzed.
- Specific and total mitochondrial GAT activity was measured.
- Samples were obtained from deceased donors between 6 and 36 hours postmortem.
Main Results:
- GAT activity was very low at birth, increasing significantly by 7 months.
- By 18 months, GAT activity in children reached levels comparable to adults.
- No statistically significant difference in GAT activity was found between children (18 months to 11 years) and adult controls.
Conclusions:
- Pediatric GAT activity is significantly lower in the first 7 months of life.
- Peak GAT activity is achieved around 18 months and maintained through adulthood.
- Delayed GAT development in children may impair the detoxification of drugs and xenobiotics.
Objective:
To study the developmental profile of glycine N-acyltransferase (GAT) in the livers of children of various ages and to compare the total and specific GAT activity with that of the adult control subjects.
Methods:
We measured the specific and the total mitochondrial activity of GAT in liver samples taken from 13 children 4 hours to 11 years of age. The samples were compared with those of control adults aged 24 to 40 years. Samples, either from liver-transplant donors or from autopsy, from those who died of a disorder not related to the liver, were obtained between 6 and 36 hours after death.
Results:
At 4 hours after birth, very low specific activity and the total liver mitochondrial activity were observed (0.19 mumol/min per milligram protein and 210 mumol/min), with a steady increase up to age 7 months (2.51 mumol/min per milligram protein and 812 mumol/min). The mean specific and total GAT activity in children (n = 5) aged 18 months to 11 years was 6.38 +/- 0.13 and 1389 +/- 43 and in control adults aged 24 to 40 years (n = 3) was 6.5 +/- 0.3 and 1461 +/- 71 mumol/min per milligram protein and mumol/min, respectively. These specific and total GAT activity values from children aged 18 months to 11 years were not statistically significant (by analysis of variance and Mann-Whitney test) in comparison with the corresponding activity values from the adult control subjects.
Conclusions:
Our results indicate that up to age 7 months, children have only 5% to 40% of liver GAT-specific activity, whereas the peak activity is achieved at 18 months and remains constant until age 40 years. The delayed development of GAT in children may thus compromise the detoxification of various drugs and xenobiotics.