Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha-tocopherol derivatives.

R.I.M. van Haaften, C.T.A. Evelo, J. Penders, M. Eijnwachter, G.R.M.M. Haenen, A. Bast

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Abstract

: Biochim Biophys Acta 2001 Jul 9;1548(1):23-8 Related Articles, Books, LinkOut


Inhibition of human glutathione S-transferase P1-1 by tocopherols and alpha-tocopherol derivatives.

Van Haaften RI, Evelo CT, Penders J, Eijnwachter MP, Haenen GR, Bast A.

Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, P.O. Box 616, 6200 MD Maastricht, Netherlands. r.vanhaaften@farmaco.unimaas.nl

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.

Original languageEnglish
Pages (from-to)23-28
Number of pages6
JournalBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology
Volume1548
DOIs
Publication statusPublished - 1 Jan 2001

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