Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha-tocopherol derivatives.
alpha-Tocopherol inhibits glutathione S-transferase P1-1 (GST P1-1) (R.I.M. van Haaften, C.T.A. Evelo, G.R.M.M. Haenen, A. Bast, Biochem. Biophys. Res. Commun. 280 (2001)). In various cosmetic and dietary products alpha-tocopherol is added as a tocopherol ester. Therefore we have studied the effect of various tocopherol derivatives on GST P1-1 activity. It was found that GST P1-1 is inhibited, in a concentration dependent manner, by these compounds. Of the compounds tested, the tocopherols were the most potent inhibitors of GST P1-1; the concentration giving 50% inhibition (IC(50)) is <1 microM. The esterified tocopherols and alpha-tocopherol quinone also inhibit the GST P1-1 activity at a very low concentration: for most compounds the IC(50) was below 10 microM. RRR-alpha-Tocopherol acetate lowered the V(max) values, but did not affect the K(m) for either 1-chloro-2,4-dinitrobenzene or GSH. This indicates that the GST P1-1 enzyme is non-competitively inhibited by RRR-alpha-tocopherol acetate. The potential implications of GST P1-1 inhibition by tocopherol and alpha-tocopherol derivatives are discussed.
Van Haaften
R I
RI
Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, P.O. Box 616, 6200 MD Maastricht, Netherlands. r.vanhaaften@farmaco.unimaas.nl
Evelo
C T
CT
Penders
J
J
Eijnwachter
M P
MP
Haenen
G R
GR
Bast
A
A
D000085:Acetates / Q000494:pharmacology; D003358:Cosmetics; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004952:Esters / Q000494:pharmacology; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D011487:Protein Conformation; D013237:Stereoisomerism; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology*
D000085:Acetates; D003358:Cosmetics; D004137:Dinitrochlorobenzene; D004952:Esters; D007527:Isoenzymes; D014810:Vitamin E; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase