Inhibition of peroxidase and catalase activities and modulation of hydrogen peroxide level by inositol phosphoglycan-like compounds
Inhibition of peroxidase and catalase activities and modulation of hydrogen peroxide level by inositol phosphoglycan-like compounds
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DOI：
10.1055/s-2007-957341
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发表时间：
2007-01-01
影响因子：
2.2
通讯作者：
Krawiec, L.
中科院分区：
文献类型：
--
作者：
Thomasz, L.;Aran, M.;Krawiec, L.
肌醇磷酸聚糖样化合物通过膜结合糖基磷酸肌醇水解产生。除了作为胰岛素作用的短期介质外，它们还抑制过氧化物酶和过氧化氢酶，增加细胞过氧化氢的浓度。虽然高浓度的过氧化氢是有毒的，但其基础水平的适度增加是不同代谢途径的信号。抑制剂位于细胞的胞质溶胶中，作用于同一组织（同源作用）和其他组织或生物体（异源作用）的过氧化物酶和过氧化氢酶。肌醇磷酸聚糖样化合物抑制具有不同辅基的过氧化物酶，即含有铁的过氧化物酶，如：甲状腺过氧化物酶、乳过氧化物酶、辣根过氧化物酶、大豆过氧化物酶;和含有硒的过氧化物酶，如谷胱甘肽过氧化物酶和2-半胱氨酸过氧化物氧还蛋白，不具有辅基。除了过氧化物酶，肌醇磷酸聚糖类化合物抑制过氧化氢酶，另一种血红素酶。抑制动力学表现出非竞争性效应。作用位点不是辅基，因为在存在或不存在过氧化氢的情况下，抑制剂不会对Soret区域中的峰产生任何影响。总之，肌醇磷酸聚糖样化合物是参与过氧化氢水平调节的过氧化物酶和过氧化氢酶的一般抑制剂，其在不同的代谢途径中作为信号转导物起作用。
Inositol phosphoglycan-like compounds are produced by the hydrolysis of the membrane bound glycosyl phosphoinositides. Besides being short term mediators of insulin action, they inhibit peroxidases and catalase, increasing the concentration of cellular hydrogen peroxide. Although high concentrations of hydrogen peroxide are toxic, moderate increases of its basal level are signals for different metabolic pathways. The inhibitor, localized in the cytosol of the cell, acts on peroxidases and catalase of the same tissue (homologous action) and of other tissues or organisms (heterologous action). The inositol phosphoglycan-like compound inhibits peroxidases with different prosthetic groups, i.e. containing iron such as: thyroid peroxidase, lactoperoxidase, horseradish peroxidase, soy bean peroxidase; and containing selenium such as glutathione peroxidase and 2-cys peroxiredoxin with no prosthetic group. Besides peroxidases, the inositol phosphoglycan-like compound inhibits catalase, another heme enzyme. The inhibition kinetics demonstrates a noncompetitive effect. The site of action is not the prosthetic group, given that the inhibitor does not produce any effect on the peak in the Soret region in the presence or absence of hydrogen peroxide. In conclusion, the inositol phosphoglycan-like compound is the general inhibitor of peroxidases and catalase involved in the modulation of hydrogen peroxide level that acts in different metabolic pathways as a signal transducer.