The human glutathione S-transferases: Developmental aspects of the GST1, GST2, and GST3 loci

Strange, Richard C.; Davis, Brian A.; Faulder, Charles G.; Cotton, William; Bain, A. D.; Hopkinson, D. A.; Hume, Robert

doi:10.1007/bf00499944

Cited by 72 publications

(43 citation statements)

References 10 publications

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“…Individuals with the 0 phenotype are identified by the absence of activity, and those with the 1 and 2 phenotypes by isoenzymes that differ in their mobilities on starch gel electrophoresis. The frequency of individuals possessing the 0 phenotype is approximately 50% (Board, 1981;Strange et al, 1984Strange et al, , 1985Laisney et al, 1984;Harada et al, 1987), which is in agreement with the population frequency calculated for GT-tSBO (Seideg~trd and Pero, 1985).…”

Section: Introductionsupporting

confidence: 69%

Identification of thetrans-stilbene oxide-active glutathione transferase in human mononuclear leukocytes and in liver as GST1

Seidegård¹,

Pero²,

Stille

1989

Biochem Genet

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A glutathione transferase from human mononuclear leukocytes with a high activity toward trans-stilbene oxide (GT-tSBO) has been studied in liver and blood from fetus and adults and in blood from neonates. Using starch gel electrophoresis, different phenotypes of GST1 have been determined, GST1 0, GST1 1, and GST1 2. As judged from activity measurements and the fact that only those individuals who express the null allele of GST1, the GST1 0, which has a low activity toward trans-stilbene oxide, it is concluded that the hepatic transferase GST1 is identical to GT-tSBO, as well as to hepatic transferase mu. In addition, it has been shown that the different genotypes of GST1 1 (GST1 1-1, GST1 1-0) and GST1 2 (GST1 2-2, GST1 2-0) can be separated by measuring the GT-tSBO activity in whole blood from the same individual. It is also demonstrated that GT-tSBO activity is much lower in fetal liver, approximately 10 times, compared with adult liver, while this activity seems to be unchanged in the blood from fetus and adults, as well as in neonates.

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Section: Introductionsupporting

confidence: 69%

Identification of thetrans-stilbene oxide-active glutathione transferase in human mononuclear leukocytes and in liver as GST1

Seidegård¹,

Pero²,

Stille

1989

Biochem Genet

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“…39 It is known that GST-M1 enzyme is not expressed until 30 weeks of gestation, but its levels increase and reach adult levels in late infancy. 40 Given the average age of patients included in this study, the expression of this enzyme among the patients enrolled should be similar to that of adult patients. The association between the GST-M1 null genotype and the adverse events of azathioprine should therefore be valid both for the young and the adult population, but studies on adult patients could be of interest.…”

Section: Discussionmentioning

confidence: 98%

Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel disease

Stocco

Martelossi

Barabino

et al. 2007

Inflammatory Bowel Diseases

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“…Many of the early studies on GST developmental expression relied on substrate probes (e.g., Strange et al, 1985), and as such, conclusions drawn regarding differential expression suffer from a lack of specificity. Nevertheless, these studies did demonstrate differences in tissue-specific GST expression as a function of development.…”

Section: Glutathione S-transferasementioning

confidence: 99%

The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms: Table 1

McCarver¹,

Hines²

2002

J Pharmacol Exp Ther

323

151

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Changes in phase II drug-metabolizing enzyme expression during development, as well as the balance between phase I and phase II enzymes, can significantly alter the pharmacokinetics for a given drug or toxicant. Although our knowledge is incomplete, many of the phase II enzymes are expressed early in development. There is evidence for glutathione S-transferase A1/A2 (GSTA1/A2), GSTM, and GSTP1 in fetal liver, lung and kidney, although tissue-specific patterns and changes with time are observed. N-Acetyltransferase 1 (NAT1) activity also has been reported throughout gestation in fetal liver, adrenal glands, lung, kidney, and intestine. Only postnatal changes in NAT1 expression were apparent. Nothing is known about human NAT2 developmental expression. Some UDP-glucuronosyltransferase and sulfotransferase isoforms also are detectable in fetal liver and other tissues by the first or second trimester, and substantial changes in isoform expression patterns, as well as overall expression levels, are observed with increasing maturity. Finally, expression of both epoxide hydrolases 1 and 2 (EPHX1 and EPHX2) is observed in fetal liver, and for the former, increased expression with time has been documented. Less is known about ontogenic molecular control mechanisms. Limited data suggest that the hepatocyte nuclear factor and CCAAT/enhancer binding protein families are critical for fetal liver drug-metabolizing enzyme expression whereas D element binding protein and related factors may regulate postnatal hepatic expression. There is a paucity of data regarding mechanisms for the onset of extrahepatic fetal expression or specific mechanisms determining temporal switches, such as those observed within the CYP3A and flavin-containing monooxygenase families.Taking advantage of electrophilic functional groups already present on the molecule, or ones introduced during phase I metabolism, the phase II drug-metabolizing enzymes (DMEs) are characterized by their ability to conjugate xenobiotics using small molecular weight, organic donor molecules such as glutathione, UDP-glucuronic acid, or acetyl coenzyme A. These reactions generally result in pharmacological inactivation or detoxification, although instances of bioactivation are known. Conjugation products also can be substrates for specific transport enzymes, thus facilitating elimination from the body. Historically, research on DMEs has placed more emphasis on those catalyzing phase I versus phase II reactions. This also has been true with respect to studies on DME developmental expression. Given the importance of the conjugation enzymes in drug and toxicant disposition and, in particular, how the balance between phase I and phase II enzymes can dramatically alter pharmacokinetics and therefore therapeutic efficacy and/or xenobiotic toxicity, this area deserves increased attention.Advances in our understanding of phase II enzyme expression during ontogeny have been hampered by many of the same problems discussed for the phase I enzymes (Hines and McCarver, 2002). These ...

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The human glutathione S-transferases: Developmental aspects of the GST1, GST2, and GST3 loci

Cited by 72 publications

References 10 publications

Identification of thetrans-stilbene oxide-active glutathione transferase in human mononuclear leukocytes and in liver as GST1

Identification of thetrans-stilbene oxide-active glutathione transferase in human mononuclear leukocytes and in liver as GST1

Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel disease

The Ontogeny of Human Drug-Metabolizing Enzymes: Phase II Conjugation Enzymes and Regulatory Mechanisms: Table 1

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