Takebe Gen, Yarimizu Junko, Saito Yoshiro, Hayashi Takaaki, Nakamura Hajime, Yodoi Junji, Nagasawa Shigeharu, Takahashi Kazuhiko
Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
J Biol Chem. 2002 Oct 25;277(43):41254-8. doi: 10.1074/jbc.M202773200. Epub 2002 Aug 15.
Glutathione peroxidase catalyzes the reduction of hydrogen peroxide and organic hydroperoxide by glutathione and functions in the protection of cells against oxidative damage. Glutathione peroxidase exists in several forms that differ in their primary structure and localization. We have also shown that selenoprotein P exhibits a glutathione peroxidase-like activity (Saito, Y., Hayashi, T., Tanaka, A., Watanabe, Y., Suzuki, M., Saito, E., and Takahashi, K. (1999) J. Biol. Chem. 274, 2866-2871). To understand the physiological significance of the diversity among these enzymes, a comparative study on the peroxide substrate specificity of three types of ubiquitous glutathione peroxidase (cellular glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, and extracellular glutathione peroxidase) and of selenoprotein P purified from human origins was done. The specific activities and kinetic parameters against two hydroperoxides (hydrogen peroxide and phosphatidylcholine hydroperoxide) were determined. We next examined the thiol specificity and found that thioredoxin is the preferred electron donor for selenoprotein P. These four enzymes exhibit different peroxide and thiol specificities and collaborate to protect biological molecules from oxidative stress both inside and outside the cells.
谷胱甘肽过氧化物酶催化谷胱甘肽还原过氧化氢和有机氢过氧化物，并在保护细胞免受氧化损伤中发挥作用。谷胱甘肽过氧化物酶以几种形式存在，它们的一级结构和定位各不相同。我们还表明，硒蛋白P具有类似谷胱甘肽过氧化物酶的活性（斋藤洋、林彻、田中明、渡边洋、铃木真、斋藤英和高桥健（1999年）《生物化学杂志》274卷，2866 - 2871页）。为了解这些酶之间多样性的生理意义，我们对三种普遍存在的谷胱甘肽过氧化物酶（细胞谷胱甘肽过氧化物酶、磷脂氢过氧化物谷胱甘肽过氧化物酶和细胞外谷胱甘肽过氧化物酶）以及从人源纯化的硒蛋白P的过氧化物底物特异性进行了比较研究。测定了它们针对两种氢过氧化物（过氧化氢和磷脂酰胆碱氢过氧化物）的比活性和动力学参数。接下来我们研究了硫醇特异性，发现硫氧还蛋白是硒蛋白P的首选电子供体。这四种酶表现出不同的过氧化物和硫醇特异性，并协同作用以保护细胞内外的生物分子免受氧化应激。
