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目的半胱氨酸蛋白酶参与了很多动植物生理过程和病理过程,是Hg2+及其化合物作用的潜在靶点。木瓜蛋白酶是半胱氨酸蛋白酶家族中最具代表性、研究最为广泛深入的一种蛋白酶,本文以木瓜蛋白酶为模型, 研究了汞等金属离子及其化合物对半胱氨酸蛋白酶活性的抑制作用。结果 Hg2+对木瓜蛋白酶活性的抑制能力很强(Ki=2×10-7 mol·L-1)。过量的还原型谷胱甘肽和半胱氨酸能够恢复木瓜蛋白酶的活性。多种金属离子(Cu2+、Ag+、Au3+、Zn2+、Cd2+、Fe3+、Mn2+、Pb2+、Yb3+)对木瓜蛋白酶的活性具有抑制能力,而且抑制能力与金属离子自身的软硬度具有良好的相关性。研究结果表明 Hg2+ 可能作用于木瓜蛋白酶的活性中心。此外,本文首次研究了汞多硫化物复合物对木瓜蛋白酶活性的抑制作用,发现其表观抑制常数(Ki= 7×10-6 mol·L-1)与柳硫汞(Ki=2.7×10-6mol·L-1)十分接近,而且其caco-2细胞单层的表观渗透能力(1.9×10-5cm/s) 也较好。结论汞多硫化物复合物可能通过与半胱氨酸蛋白酶或者其它含巯基蛋白分子作用,发挥生物学活性。本文的研究工作可能有助于阐明汞化合物( 特别是朱砂等不溶性汞化合物) 的毒理及药理作用的机制。
The purpose of cysteine protease involved in many plant and animal physiological processes and pathological processes, is a potential target Hg2 + and its compounds. Papain is one of the most representative and most extensively studied proteases in the cysteine protease family. In this paper, papain was used as a model to study the inhibition of cysteine protease activity by metal ions such as mercury and their compounds . Results Hg2 + had a strong inhibitory activity on papain activity (Ki = 2 × 10-7 mol·L-1). Excess glutathione and cysteine restore papain activity. Many kinds of metal ions (Cu2 +, Ag +, Au3 +, Zn2 +, Cd2 +, Fe3 +, Mn2 +, Pb2 +, Yb3 +) have inhibitory activity on the activity of papain, and the inhibition ability has a good correlation with the hardness of metal ions themselves. The results show that Hg2 + may act on the active center of papain. In addition, this paper firstly studied the inhibitory effect of mercury polysulfide complex on papain activity and found that the apparent inhibition constant (Ki = 7 × 10-6 mol·L-1) and thimerosal (Ki = 2.7 × 10 -6 mol·L-1), and the apparent permeability (1.9 × 10 -5 cm / s) of the caco-2 cell monolayer was also good. Conclusions Mercury polysulfide complexes may exert their biological activity through interaction with cysteine protease or other thiol-containing proteins. The research work in this article may help elucidate the toxicological and pharmacological mechanisms of mercury compounds (especially insoluble mercury compounds such as cinnabar).