Developmental profile of mitochondrial glycine N -acyltransferase in human liver

doi:10.1016/S0022-3476(97)70293-2

The Journal of Pediatrics

Volume 130, Issue 6, June 1997, Pages 1003-1007

https://doi.org/10.1016/S0022-3476(97)70293-2 Get rights and content

Abstract

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 μmol/min per milligram protein and 210 mmol/min), with a steady increase up to age 7 months (2.51 μmol/min per milligram protein and 812 mmol/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 μmol/min per milligram protein and μmol/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. (J Pediatr 1997;130:1003-7)

Section snippets

METHODS

We measured the specific and the total mitochondrial activity of GAT in liver samples taken from 13 male and female children aged 4 hours to 11 years and compared the activity with that of adults aged 24 to 40 years. Our samples were obtained between 6 and 36 hours after death, either from liver-transplant donors or from autopsy samples obtained from children (Table I).

. Samples used in the measurement of human liver mitochondrial GAT activity during development

Age	Sex	Postmortem interval	Cause of

RESULTS

The developmental profiles constructed from the data on the specific activity in the partially purified preparation and the total liver mitochondrial content are presented in the Figure, panels A and B , respectively.

Figure. Ontogeny of human liver mitochondrial GAT in (A) the 40% to 60% ammonium sulfate precipitated protein fraction and (B) the total liver mitochondrial lysate in children of various ages.

In the sample from a child who died 4 hours after birth, very low specific activity and

DISCUSSION

The developmental profiles determined in this study indicate that a plateau of the liver GAT activity is reached at age 18 months, and no appreciable differences are observed between ages 18 months and 11 years. Because no samples were available to us between ages 7 to 18 months, it is difficult to pinpoint exactly the age at which the peak of GAT development was reached. By using mitochondrial lysates, James and Bend ¹⁸ observed very little enzyme activity in the liver of fetal and early

Acknowledgements

We are grateful to Dr. Jean Michaud, head of the Division of Pathology, Hôpital Sainte-Justine, Montréal, for his help and cooperation in providing the autopsy samples from children of various ages.

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GLYAT expression is underdeveloped in newborns, with children under seven months of age having 5% to 40% of normal GLYAT activity. GLYAT enzyme activity reaches its peak at about 18 months of age, stays at this level until approximately the age of 40, and then declines slightly in the elderly (Temellini et al., 1993; Mawal et al., 1997). It has also recently been demonstrated that GLYAT expression is transcriptionally down-regulated in hepatocellular carcinoma specimens, and that diet influences the expression of GLYAT in the livers of rats (Matsuo et al., 2012; Wen et al., 2013).
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In the present study, we identified 5 novel single nucleotide polymorphisme (SNPs) in the gene of glycine N-acyltransferase (GlyAT) by resequencing the entire coding region and the exon-intron junctions from 95 Japanese individuals. The allelic frequencies of 5 novel SNPs were 0.016 for − 695T > C, 0.021 for − 260C>T, 0.005 for 290C>T, 0.005 for 19371G>A, and 0.005 for 21289G>A. Genetic variants of − 979C>G and 21409A>G were in perfect linkage disequilibrium with 21364A>G and 21422C>T, respectively. The nonsynonymous SNP, 21289G > A (Arg131His) in exon 5, was also genotyped in 31 Caucasian individuals, but none of them possessed 21289A (131His) allele.

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^☆☆: Supported by a grant (MT-9124) from the Medical Research Council of Canada and by Biopedia.

^★: Reprint requests: Ijaz A. Qureshi, PhD, Genetique Medicale, Centre de Recherche, Hôpital Sainte-Justine, 3175 Côte Sainte Catherine, Montréal, Québec H3T 1C5, Canada.

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Developmental profile of mitochondrial glycine N -acyltransferase in human liver☆,☆☆,★

Abstract

Section snippets

METHODS

RESULTS

DISCUSSION

Acknowledgements

Lancet

Biochem Pharmacol

J Biol Chem

Pharmacol Ther

Biochem Biophys Res Commun

Methods Enzymol

J Biol Chem

J Biochem Biophys Methods

Clin Chim Acta

J Pediatr

Lancet

Evidence for a medium-chain fatty acid: coenzyme A ligase (adenosine monophosphate) that activates salicylate

Mol Pharmacol