van Haaften Rachel I M, Haenen Guido R M M, Evelo Chris T A, Bast Aalt
Department of Pharmacology and Toxicology, Faculty of Medicine, Universiteit Maastricht, The Netherlands.
IUBMB Life. 2002 Aug;54(2):81-4. doi: 10.1080/15216540214315.
Tocopherols and tocotrienols are food ingredients that are believed to have a positive effect on health. The most studied property of both groups of compounds is their antioxidant action. Previously, we found that tocopherols and diverse tocopherol derivatives can inhibit the activity of human glutathione S-transferase P1-1 (GST P1-1). In this study we found that GST P1-1 is also inhibited, in a concentration-dependent manner, by alpha- and gamma-tocotrienol. The concentration giving 50% inhibition of GST P1-1 is 1.8 +/- 0.1 microM for alpha-tocotrienol and 0.7 +/- 0.1 microM for gamma-tocotrienol. This inhibition of GST P1-1 is noncompetitive with respect to both substrates CDNB and GSH. We also examined the 3D structure of GST P1-1 for a possible tocopherol/tocotrienol binding site. The enzyme contains a very hydrophobic pit-like structure where the phytyl tail of tocopherols and tocotrienols could fit in. Binding of tocopherol and tocotrienol to this hydrophobic region might lead to bending of the 3D structure. In this way tocopherols and tocotrienols can inhibit the activity of the enzyme; this inhibition can have far-reaching implications for humans.
生育酚和生育三烯酚是被认为对健康有积极影响的食品成分。这两类化合物研究最多的特性是它们的抗氧化作用。此前，我们发现生育酚和多种生育酚衍生物能够抑制人谷胱甘肽S-转移酶P1-1（GST P1-1）的活性。在本研究中，我们发现α-生育三烯酚和γ-生育三烯酚也能以浓度依赖的方式抑制GST P1-1。对GST P1-1产生50%抑制作用的α-生育三烯酚浓度为1.8±0.1微摩尔，γ-生育三烯酚为0.7±0.1微摩尔。这种对GST P1-1的抑制作用对于两种底物CDNB和GSH而言是非竞争性的。我们还研究了GST P1-1的三维结构，以寻找可能的生育酚/生育三烯酚结合位点。该酶含有一个非常疏水的坑状结构，生育酚和生育三烯酚的植基尾巴可以嵌入其中。生育酚和生育三烯酚与这个疏水区域的结合可能会导致三维结构弯曲。通过这种方式，生育酚和生育三烯酚可以抑制该酶的活性；这种抑制作用可能对人类产生深远影响。
