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Detoxification of Styrene Oxide by Human Liver Glutathione Transferase

Division of Clinical Pharmacology, University Hospital, S-751 85 Uppsala

M. Warholm

Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, S-106 91 Stockholm, Unit of Occupational Toxicology, National Board of Occupational Safety and Health, S-171 84 Solna, Sweden

C. Guthenberg

Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, S-106 91 Stockholm

B. Mannervik

Department of Biochemistry, Arrhenius Laboratory, University of Stockholm, S-106 91 Stockholm

A. Rane

Division of Clinical Pharmacology, University Hospital, S-751 85 Uppsala

Cytosolic glutathione transferase (GST) was investigated in four human livers. The profile of GST activity was determined by isoelectric focusing using 1-chloro-2,4-dinitrobenzene as the electrophilic substrate. Three livers contained at least one basic and a near-neutral isoenzyme (GST µ). GSTµ was not detectable in the fourth liver. The kinetics of GST with styrene oxide as the electrophilic substrate were studied in the cytosolic fraction, with the pooled fractions from isoelectric focusing containing high activity of GSTµ transferase, and with GSTµ purified to homogeneity. The cytosol obeyed Michaelis-Menten kinetics when styrene oxide was used as the variable substrate. The average (± s.e.m.) of the Vmax and K_m were 21.9 ± 7.9 nmol min ^-1 mg^-1 and 4.9 ± 0.4 mM, respectively. At varying concentrations of glutathione, the enzyme did not obey Michaelis-Menten kinetics. Such kinetics were also observed with the fractions from isoelectric focusing and with the homogeneous GSTµ fraction. The Eadie-Hofstee plot showed two phases: one with a low and another with a high K_m value.

The apparent K _m values for the cytosol were 0.035 ± 0.022 and 0.88 ± 0.36 mM. The kinetic pattern of purified GSTµ is consistent with that found in the cytosol.

Human & Experimental Toxicology, Vol. 6, No. 6, 483-489 (1987)
DOI: 10.1177/096032718700600606


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