Hereditary interindividual differences in the glutathione transferase activity towards trans-stilbene oxide in resting human mononuclear leukocytes are due to a particular isozyme(s).
We have shown earlier that there are large, hereditary interindividual differences in the cytosolic glutathione transferase activity towards trans-stilbene oxide in human mononuclear leukocytes. In the present study we ask whether these differences reflect the presence or absence of a particular isozyme(s) of glutathione transferase. First, in order to measure the high glutathione transferase activity optimally it was necessary to modify our previous assay by increasing the concentration of reduced glutathione from 3 to 5 mM and of the substrate from 50 to 250 microM. It was then found that the low activity demonstrates an apparent Km for trans-stilbene oxide of 28.3 microM, whereas the corresponding value for the high activity was 127 microM. Secondly, it was found that while glutathione transferase activity towards trans-stilbene oxide in different individuals segregated into three groups, low, high and very high, glutathione transferase activity towards 1-chloro-2,4-dinitrobenzene in these same mononuclear leukocyte fractions formed only a single group with no tendency towards such segregation. Thirdly, the SDS-poly-acrylamide gel electrophoretic pattern obtained with the supernatant fraction from mononuclear cells demonstrating high glutathione transferase activity towards trans-stilbene oxide contained a band of 25 000 molecular weight which was either absent or present at a much lower level in cells demonstrating low activity. We conclude that high activity towards trans-stilbene oxide in circulating, resting human mononuclear cells is catalyzed by a particular isozyme(s) of glutathione transferase. cis-Stilbene oxide, styrene oxide and, possibly, benzo[a]pyrene 4,5-oxide are also substrates for this isozyme(s).
D004137:Dinitrochlorobenzene / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000097:blood*; D006801:Humans; D007206:Individuality; D007527:Isoenzymes / Q000097:blood*; D007700:Kinetics; D007962:Leukocytes / Q000201:enzymology*; D013267:Stilbenes / Q000378:metabolism*; D013379:Substrate Specificity
D004137:Dinitrochlorobenzene; D007527:Isoenzymes; D013267:Stilbenes; D005982:Glutathione Transferase; C025906:stilbene oxide