A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P.
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.
Takebe
Gen
G
Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12 Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Yarimizu
Junko
J
Saito
Yoshiro
Y
Hayashi
Takaaki
T
Nakamura
Hajime
H
Yodoi
Junji
J
Nagasawa
Shigeharu
S
Takahashi
Kazuhiko
K
D005979:Glutathione Peroxidase / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007700:Kinetics; D011506:Proteins / Q000378:metabolism*; D051149:Selenoprotein P; D051140:Selenoproteins; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase