alpha-Tocopherol inhibits human glutathione S-transferase pi.
alpha-Tocopherol is the most important fat-soluble, chain-breaking antioxidant. It is known that interplay between different protective mechanisms occurs. GSTs can catalyze glutathione conjugation with various electrophiles, many of which are toxic. We studied the influence of alpha-tocopherol on the activity of the cytosolic pi isoform of GST. alpha-Tocopherol inhibits glutathione S-transferase pi in a concentration-dependent manner, with an IC(50)-value of 0.5 microM. At alpha-tocopherol additions above 3 microM there was no GST pi activity left. alpha-Tocopherol lowered the V(max) values, but did not affect the K(m) for either CDNB or GSH. This indicates that the GST pi enzyme is noncompetitively inhibited by alpha-tocopherol. An inhibition of GST pi by alpha-tocopherol may have far-reaching implications for the application of vitamin E.
van Haaften
R I
RI
Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, 6200 MD Maastricht, The Netherlands.
Evelo
C T
CT
Haenen
G R
GR
Bast
A
A
D000975:Antioxidants / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D004137:Dinitrochlorobenzene; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005978:Glutathione; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D013379:Substrate Specificity; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D004137:Dinitrochlorobenzene; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D014810:Vitamin E; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione