人胎盘谷胱甘肽S-转移酶动力学及抑制剂的研究

研究了人胎盘型谷胱甘肽S-转移酶(GST-π)的动力学。底物GSH和1-氯-2,4-二硝基苯(CDNB)的km分别为0.109和0.870mmol/L。苯唑青霉素和先锋霉素Ⅰ能抑制GST—π,以先锋霉素较明显,属非竞争性抑制。溴磺酜对CDNB也是非竞争作用,但胆红素则对CDNB竞争而对GSH非竞争地抑制酶活力。S-正辛烷和S-正已烷谷胱甘肽与GSH竞争而与CDNB非竞争地抑制GST-π。已充分证明GST-π所催化的双底物反应属随机顺序机制。化学修饰实验发现:巯基、胍基、氨基、羧基和吲哚基可能参与酶活性中心的组成。

Studies on the Kinetics and Inhibitors Of Human Placenta Glutathione S-Transferase

The kinetics and inhibitors of purified glutathione S-transf erase from-human placenta (GST-π) were studied. The Km of substrate glutathione(GSH) and 1-chlore-2,4-dinitrobenzene (CDNB) were 0.109 and 0.870 m mol/L respectively, Oxacillin and cephalothin were shown to inhnbit GST-π, and inhibition with cephalothin was more obvious and noncompetitive. Bromosulfophthalein was also noncompetitive inhibitor with respect to CDNB, whereas bilirubin was competitive with CDNB and noncompetitive with GSH in inhibiting GST-π. Two derivatives of GSH, S-n-octy-lglutathione and S-n-hexylglutathione, were competitively with GSH and noncompe-titively with CDNB to inhibit GST-π. It was well proved that the mechanism of GST-π catalyzed reaction was random sequential. Chemical modification studies showed that the sulfhydryl, guanido, amino, carboxyl and indolyl groups may par ticipate in the active center of the enzyme.