Glutathione S-Transferase Activity in Human Fetal and Adult Tissues

Mukhtar, Hasan; Zoetemelk, C. E. M.; Baars, A.J.; Wijnen, Juul T.; Blankenstein-Wijnen, Lucie M.M.; Khan, Meera; Breimer, D. D.

doi:10.1159/000137507

Cited by 33 publications

(6 citation statements)

References 7 publications

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“…We thus investigated these possibilities by purification of the basic and acidic transfer ases from the human fetal liver and by studying their kinetics. styrene oxide [Pacifici andRane, 1981, 1982;, and l-chloro-2,4-dinitrobenzene [Warholm et al, 198 lb;Mukhtar et al, 1981;Pacifici et al, 1986] as substrates.…”

Section: Introductionmentioning

confidence: 99%

Conjugation of Styrene Oxide by the Basic and Acidic Forms of Glutathione Transferase in the Human Fetal Liver

Pacifici

Guthenberg²,

Warholm³

et al. 1988

Dev Pharmacol Ther

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Two forms of glutathione transferase were isolated by means of isoelectric focusing of human fetal liver cytosol preparations. The enzyme activity was measured with l-chloro-2,4-dinitrobenzene as the electrophilic substrate. One peak focused at pH 9-10 (basic form) and the other at pH 4-5 (acidic form). The basic and the acidic forms are representatives of glutathione transferase classes a and n, respectively. These classes constitute two of the three classes defined for cytosolic forms of the enzyme in several mammalian species [Mannervik et al., Proc. natn. Acad. Sci. USA 82: 7202-7206, 1985], Only the basic fraction isolated from human fetal liver catalyzed the conjugation of styrene oxide with glutathione at a significant rate. The kinetics of this form were studied keeping the concentration of styrene oxide constant (6 mM) and varying the glutathione concentration from 0.05 to 25 mM. The enzyme activity displayed non-Michaelis-Menten kinetics. The basic and acidic forms of glutathione transferase from a fetal liver were purified to homogeneity. Both purified forms catalyzed the conjugation of glutathione with styrene oxide. The kinetics were studied at varying glutathione concentrations and for both forms, it was found to be of a non-Michaelis-Menten type. The results are consistent with previous findings in the cytosolic fraction [Pacifici et al., Biochem. Pharmac. 30: 3367-3371, 1981] and show that the non- Michaelian kinetics observed with glutathione in human fetal liver cytosol are reflections of the intrinsic properties of the basic as well as the acid form of this enzyme and not primarily depending on the simultaneous catalytic action of the two forms.

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Section: Introductionmentioning

confidence: 99%

Conjugation of Styrene Oxide by the Basic and Acidic Forms of Glutathione Transferase in the Human Fetal Liver

Pacifici

Guthenberg²,

Warholm³

et al. 1988

Dev Pharmacol Ther

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“…The metabolic fate of epoxides within the organism involves two major pathways: the conjugation with glutathione catalyzed by glutathione S-transferase [4,6] and the hydration to glycol or dihydrodiol by the microsomal epoxide hydrolase [21]. The first pathway has been demonstrated in sev eral human fetal tissues both with styrene oxide [24] and l-chloro-2.4-dinitrobenzene [18] as substrate, and its kinetics with respect to glutathione and styrene oxide has been characterized [23]. Styrene oxide hydration has also been demonstrated in several extrahepatic organs of the human fetus [24].…”

Section: Introductionmentioning

confidence: 99%

Epoxide Hydrolase in Human Fetal Liver

Pacifici

Rane

1983

Pharmacology

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Epoxide hydrolase activity towards styrene oxide was measured in the microsomal fraction of 20 human fetal livers. The enzymatic activity was 5.60 ± 0.52 nmol/ min/mg (mean ± SE) which is about 40 % of the previously reported value in human adult liver microsomes. No relation between enzymatic activity and fetal age was observed. The kinetics of the enzyme were studied in 6 different livers and found to obey Michaelis-Menten kinetics. The K_m ranged between 0.25 and 0.54 mmol/l and V_max between 7.2 and 16.7 nmol/min/mg microsomal protein. The enzyme was inhibited both by 111-trichloropropene-2,3-oxide (TCPO; 0.25 mmol/l) and benzo(a)pyrene-4,5-oxide (BPO; 0.2 mmol/l). Those substances inhibited the epoxide hydrolase by 61 and 14%, respectively, at 1 mmol/l styrene oxide. Thus TCPO was considerably more potent as an inhibitor of the fetal liver styrene oxide hydrolase. Lineweaver-Burk plots of the inhibition data revealed that TCPO exerts an uncompetitive mixed type of inhibition.

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“…periods and increase gradually with age up to adulthood [23]. The GSR activity of lymphocytes derived from mice at ages 2, 9 and 24 months is pre sented in table III.…”

Section: Resultsmentioning

confidence: 99%

Changes in Glutathione, Glutathione Reductase and Glutathione-S-Transferase as a Function of Cell Concentration and Age

et al. 1987

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The activities of glutathione-S-transferase (GST) and glutathione reductase (GSR) in mouse lymphocytes as a function of cell concentration and age were determined. Lymphocytes from 2-, 9- and 24-month-old mice were isolated and the activity of GST was determined spectrophotometrically using 1-chloro-2,4-dinitrobenzene as the substrate. Lymphocyte concentrations of 0.44, 0.75 and 0.55 × 10⁶ cells/ml were found to be optimal for assaying GST in 2-, 9- and 24-month-old mice, respectively. Determination of GSR activity was based on NADPH reduction of oxidized glutathione and cell concentrations of 0.29, 0.30 and 0.22 × 10⁶ cells/ml were chosen for assaying the enzyme activity for the three age groups, respectively. Glutathione levels and GSR activity of mice lymphocytes were higher in 2- and 24-month-old mice as compared to 9-month-old animals. However, GST activity of mouse lymphocytes was low in 2- and 9-month-old mice and increased significantly in 24-month-old animals.

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Glutathione S-Transferase Activity in Human Fetal and Adult Tissues

Cited by 33 publications

References 7 publications

Conjugation of Styrene Oxide by the Basic and Acidic Forms of Glutathione Transferase in the Human Fetal Liver

Conjugation of Styrene Oxide by the Basic and Acidic Forms of Glutathione Transferase in the Human Fetal Liver

Epoxide Hydrolase in Human Fetal Liver

Changes in Glutathione, Glutathione Reductase and Glutathione-S-Transferase as a Function of Cell Concentration and Age

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