Department of Chemical Sciences and Technologies, University of Rome, Tor Vergata, Rome, Italy.
FEBS Lett. 2011 Jan 21;585(2):341-5. doi: 10.1016/j.febslet.2010.12.009. Epub 2010 Dec 14.
Glutathione transferase reaches 0.5-0.8 mM concentration in the cell so it works in vivo under the unusual conditions of, [S]≪[E]. As glutathione transferase lowers the pK(a) of glutathione (GSH) bound to the active site, it increases the cytosolic concentration of deprotonated GSH about five times and speeds its conjugation with toxic compounds that are non-typical substrates of this enzyme. This acceleration becomes more efficient in case of GSH depletion and/or cell acidification. Interestingly, the enzymatic conjugation of GSH to these toxic compounds does not require the assumption of a substrate-enzyme complex; it can be explained by a simple bimolecular collision between enzyme and substrate. Even with typical substrates, the astonishing concentration of glutathione transferase present in hepatocytes, causes an unusual "inverted" kinetics whereby the classical trends of v versus E and v versus S are reversed.
谷胱甘肽转移酶在细胞中的浓度达到 0.5-0.8mM，因此在[S]≪[E]的特殊条件下在体内发挥作用。由于谷胱甘肽转移酶降低了与活性位点结合的谷胱甘肽 (GSH) 的 pK(a)，它将胞质中去质子化 GSH 的浓度增加了约五倍，并加速了其与非典型酶底物的毒性化合物的结合。在 GSH 耗竭和/或细胞酸化的情况下，这种加速变得更加有效。有趣的是，GSH 与这些毒性化合物的酶促结合不需要假定底物-酶复合物；它可以通过酶和底物之间的简单双分子碰撞来解释。即使对于典型的底物，肝细胞中存在的惊人浓度的谷胱甘肽转移酶也会导致异常的“倒置”动力学，其中经典的 v 对 E 和 v 对 S 的趋势被反转。
