胆红素对人胎盘谷胱甘肽S-转移酶的别构效应

The Allosteric Effect of Bilirubin on Human Placenta Glutathione S-transferase

胆红素是人胎盘谷胱甘肽S—转移酶(GST—π)的别构效应剂,在胆红素存在下,底物谷胱甘肽(GSH)呈同促正协同效应:胆红素浓度愈高,Hill氏系数(n_H)也愈大,胆红素本身对酶的结合也呈同促正协同效应。胆红素还能加速GST-π在缺乏疏基保护剂时的自然失活,加速GST-π的氨基被2,4,6—三硝基苯磺酸(TNBS)、胍基被丁二酮以及羧基被N-乙基-N’-(3-二甲胺基丙基)羧二亚胺(EDC)的修饰,但却抑制N-乙基顺丁二酰亚胺(NEMI)对疏基的修饰,胆红素这种对失活作用的影响可能和胆红素引起GST-π空间构象的变化有关,对其他可能性也作了讨论。

Bilirubin is an allosteric inhibitor of human placenta glutathione S-tran sferase(GST-π) .In the presence of bilirubin, the binding of substrate GSH to GST-π was shown to be homotropic positive cooperation. The higher the bilirubin concentration was, the higher the Hill's constant (nH). Bilirubin itself was also a homo tropic positive cooperative ligand with respect to GST-π. Bilirubin could accelerate the natural inactivation of GST-π in the absence of sulfhydryl group protecting reagent, and the modification of amino-, guanidino and carboxyl-groups by 2,4,6-trinitrobenzene sulphonic acid (TNBS), diacetyl and l-ethyl-3-(3-dimethylamino-propyl)-carbodiimide (EDC) respectively .However, bilirubin conld inhibit the modification of sulfhydryl group by N-ethyl-maleimide (NEMI). These effects of bilirubin on the modification reactions may be the result of the conformation alteration of GST-π caused by bilirubin binding. Other posibilities were also discussed.