Abstract
The present state of knowledge on glutathione peroxidases (GPxs) is reviewed with particular emphasis on general catalytic principles and the biology of mammalian glutathione peroxidases. GPxs make up a ubiquitous family of proteins defined by sequence homology, the common functional denominator being their ability to reduce hydroperoxides by thiols. Catalysis is mediated by an active-site selenocysteine or cysteine. Eight distinct GPxs have been identified in mammals, five of them being selenoproteins in man. While glutathione specificity prevails in vertebrate GPxs, thioredoxins or related redoxins appear to be common substrates in plant, bacterial and protist GPxs. Specific reactions of GPxs with other protein thiols are also observed. The basic catalytic scheme allows the enzymes to adopt diversified biological roles ranging from defence against peroxide challenge, redox regulation of metabolic processes and transcription, apoptosis to cellular differentiation. The roles of the individual mammalian GPxs are discussed in the light of distinct substrate specificities, distribution, subcellular compartmentation, expression patterns and data from inverse genetics. It is outlined that the multiple coexisting GPxs and functionally related peroxiredoxins likely build up a system of enzymes that, with discrete functional overlap, complement each other in meeting specific biological tasks far beyond fighting oxidative stress.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Flohé L, Günzler WA, Schock HH (1973) FEBS Lett 32: 132
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG (1973) Science 179: 588
Flohé L (2009) Biochim Biophys Acta 1790: 1389
Tujebajeva RM, Copeland PR, Xu XM, Carlson BA, Harney JW, Driscoll DM, Hatfield DL, Berry MJ (2000) EMBO Rep 1: 158
Yoshizawa S, Böck A (2009) Biochim Biophys Acta 1790: 1404
Xu XM, Carlson BA, Zhang Y, Mix H, Kryukov GV, Glass RS, Berry MJ, Gladyshev VN, Hatfield DL (2007) Biol Trace Elem Res 119: 234
Allmang C, Wurth L, Krol A (2009) Biochim Biophys Acta 1790: 1415
Squires JE, Berry MJ (2008) IUBMB Life 60: 232
Maiorino M, Roche C, Kiess M, Koenig K, Gawlik D, Matthes M, Naldini E, Pierce R, Flohé L (1996) Eur J Biochem 238: 838
Salinas G, Lobanov AV, Gladyshev VN (2006) In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 355
Bae YA, Cai GB, Kim SH, Zo YG, Kong Y (2009) BMC Evol Biol 9: 72
Cossio-Bayugar R, Niranda E, Holman PJ (2005) Insect Biochem, Mol, Biol 35: 1378
Gladyshev VN (2006) In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 99
Maiorino M, Ursini F, Bosello V, Toppo S, Tosatto SC, Mauri P, Becker K, Roveri A, Bulato C, Benazzi L, De Palma A, Flohé L (2007) J Mol Biol 365: 1033
Schlecker T, Comini MA, Melchers J, Ruppert T, Krauth-Siegel RL (2007) Biochem J 405: 445
Delaunay A, Pflieger D, Barrault MB, Vinh J, Toledano MB (2002) Cell 111: 471
Flohé L, Günzler W, Jung G, Schaich E, Schneider F (1971) Hoppe Seylers Z Physiol Chem 352: 159
Godeas C, Tramer F, Micali F, Roveri A, Maiorino M, Nisii C, Sandri G, Panfili E (1996) Biochem Mol Med 59: 118
Maiorino M, Roveri A, Benazzi L, Bosello V, Mauri P, Toppo S, Tosatto SC, Ursini F (2005) J Biol Chem 280: 38395
Tosatto SC, Bosello V, Fogolari F, Mauri P, Roveri A, Toppo S, Flohé L, Ursini F, Maiorino M (2008) Antioxid Redox Signal 10: 1515
Ursini F, Heim S, Kiess M, Maiorino M, Roveri A, Wissing J, Flohé L (1999) Science 285: 1393
Mauri P, Benazzi L, Flohé L, Maiorino M, Pietta PG, Pilawa S, Roveri A, Ursini F (2003) Biol Chem 384: 575
Toppo S, Vanin S, Bosello V, Tosatto SC (2008) Antioxid Redox Signal 10: 1501
Lawrence RA, Burk RF (1976) Biochem Biophys Res Commun 71: 952
Saito Y, Sato N, Hirashima M, Takebe G, Nagasawa S, Takahashi K (2004) Biochem J 381: 841
Schremmer B, Manevich Y, Feinstein SI, Fisher AB (2007) In: Flohé L, Harris JR (eds) Peroxiredoxin Systems, Structure and Functions. Springer, New York, Subcell Biochem, 44: 317
Toppo S, Flohé L, Ursini F, Vanin S, Maiorino M (2009) Biochim Biophys Acta 1790: 1486
Trujillo M, Ferrer-Sueta G, Thomson L, Flohé L, Radi R (2007) In: Flohé L, Harris JR (eds) Peroxiredoxin Systems, Structure and Functions. Springer, New York, Subcell Biochem, 44: 83
Sunde RA (2006) In: Hatfield, DL, Berry, MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 149
Flohé L, Brigelius-Flohé R (2006) In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 161
Brigelius-Flohé R (2006) Biol Chem 387: 1329
Fourquet S, Huang ME, D’Autreaux B, Toledano MB (2008) Antioxid Redox Signal 10: 1565
Flohé L (2007) Biol, Chem 388: 987
Boitani C, Puglisi R (2008) In: Cheng CY (ed) Molecular Mechanisms in Spermatogenesis. Springer, New York: 65
Nakagawa Y (2004) Biol Pharm Bull 27: 956
Loscalzo J (2008) Cell Metab 8: 182
Beck MA (2006) In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 287
Schmutzler C, Mentrup B, Schomburg L, Hoang-Vu C, Herzog V, K.hrle J (2007) Biol Chem 388: 1053
Schweizer U, Schomburg L (2006) In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 233
Hatfield DL, Berry MJ, Gladyshev VN (eds) (2006) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York
Flohé L, Harris JR (2007) In: Flohé L, Harris JR (eds) Peroxiredoxin Systems, Structure and Functions. Springer, New York, Subcell Biochem, 44: 1
Ostwald W (1906) Leitlinien der Chemie, Sieben gemeinverständliche, Vorträge aus der Geschichte der Chemie. Akademische Verlagsgesellschaft m, b H, Leipzig: 274
Dalziel K (1957) Acta Chem Scand 11: 1706
Flohé L, Loschen G, Günzler WA, Eichele E (1972) Hoppe Seylers Z Physiol Chem 353: 987
Takebe G, Yarimizu J, Saito Y, Hayashi T, Nakamura H, Yodoi J, Nagasawa S, Takahashi K (2002) J Biol Chem 277: 41254
Maiorino M, Roveri A, Gregolin C, Ursini F (1986) Arch Biochem Biophys 251: 600
Kehr S, Malinouski M, Finney L, Vogt S, Labunskyy VM, Kasaikina MV, Carlson BA, Zhou Y, Hatfield DL, Gladyshev VN (2009) J Mol Biol 389: 808
Winterbourn CC, Metodiewa D (1999) Free Radic Biol Med 27: 322
Maiorino M, Aumann KD, Brigelius-Flohé R, Doria D, van den Heuvel J, McCarthy J, Roveri A, Ursini F, Flohé L (1995) Biol Chem Hoppe Seyler 376: 651
Ma LH, Takanishi CL, Wood MJ (2007) J Biol Chem 282: 31429
Rocher C, Lalanne JL, Chaudière J (1992) Eur J Biochem 205: 955
Epp O, Ladenstein R, Wendel A (1983) Eur J Biochem 133: 51
Koh CS, Didierjean C, Navrot N, Panjikar S, Mulliert G, Rouhier N, Jacquot JP, Aubry A, Shawkataly O, Corbier C (2007) J Mol Biol 370: 512
Jung BG, Lee KO, Lee SS, Chi YH, Jang HH, Kang SS, Lee K, Lim D, Yoon SC, Yun DJ, Inoue Y, Cho MJ, Lee SY (2002) J Biol Chem 277: 12572
Poole L (2007) In: Flohé L, Harris JR (eds) Peroxiredoxin Systems, Structure and Functions. Springer, New York, Subcell Biochem, 44: 61
Ursini F (2009) Personal communication
Sies H (1994) Methods Enzymol 234: 476
Salmeen A, Andersen JN, Myers MP, Meng TC, Hinks JA, Tonks NK, Barford D (2003) Nature 423: 769
van Montfort RL, Congreve M, Tisi D, Carr R, Jhoti H (2003) Nature 423: 773
Yang J, Groen A, Lemeer S, Jans A, Slijper M, Roe SM, den Hertog J, Barford D (2007) Biochemistry 46: 709
Ursini F, Maiorino M, Brigelius-Flohé R, Aumann KD, Roveri A, Schomburg D, Flohé L (1995) Methods Enzymol 252: 38
Aumann KD, Bedorf N, Brigelius-Flohé R, Schomburg D, Flohé L (1997) Biomed Environ Sci 10: 136
Esworthy RS, Chu FF, Geiger P, Girotti AW, Doroshow JH (1993) Arch Biochem Biophys 307: 29
Bjørnstedt M, Xue J, Huang W, Akesson B, Holmgren A (1994) J Biol Chem 269: 29382
Grossmann A, Wendel A (1983) Eur J Biochem 135: 549
Sevanian A, Muakkassah-Kelly SF, Montestruque S (1983) Arch Biochem Biophys 223: 441
Flohé L (1989) In: Dolphin D, Poulson R, Avramovic O (eds) Glutathione: Chemical,Biochemical and Medical Aspects-Part A. John Wiley & Sons, Inc: 643
Flohé L, Schlegel W (1971) Hoppe Seylers Z Physiol Chem 352: 1401
Mills GC (1957) J biol Chem 229: 189
Beutler E (1983) Biomed Biochim Acta 42: S234
Ho YS, Magnenat JL, Bronson RT, Cao J, Gargano M, Sugawara M, Funk CD (1997) J Biol Chem 272: 16644
Beck MA, Shi Q, Morris VC, Levander OA (1995) Nat Med 1: 433
Beck MA (2006) In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 287
Li W, Beck MA (2007) Exp Biol Med (Maywood) 232: 412
Kretz-Remy C, Mehlen P, Mirault ME, Arrigo AP (1996) J Cell Biol 133: 1083
Sandstrom PA, Murray J, Folks TM, Diamond AM (1998) Free Radic Biol Med 24: 1485
Mirochnitchenko O, Weisbrot-Lefkowitz M, Reuhl K, Chen L, Yang C, Inouye M (1999) J Biol Chem 274: 10349
Lu YP, Lou YR, Yen P, Newmark HL, Mirochnitchenko OI, Inouye M, Huang MT (1997) Cancer Res 57: 1468
McClung JP, Roneker CA, Mu W, Lisk DJ, Langlais P, Liu F, Lei XG, (2004) Proc Natl Acad Sci USA 101: 8852
Fu Y, Sies H, Lei XG (2001) J Biol Chem 276: 43004
Briviba K, Kissner R, Koppenol WH, Sies H (1998) Chem Res Toxicol 11: 1398
Jiang D, Akopian G, Ho YS, Walsh JP, Andersen JK (2000) Exp Neurol 164: 257
Jornot L, Junod AF (1997) Biochem J 326: 117
Merante F, Altamentova SM, Mickle DA, Weisel RD, Thatcher BJ, Martin BM, Marshall JG, Tumiati LC, Cowan DB, Li RK (2002) Mol Cell Biochem 229: 73
Pinto RE, Bartley W (1969) Biochem J 115: 449
Vina J, Sastre J, Pallardo FV, Gambini J, Borras C (2008) Biol Chem 389: 273
Throm SL, Klemsz MJ (2003) J Leukoc Biol 74: 111
Wu Y, Zhang X, Bardag-Gorce F, Robel RC, Aguilo J, Chen L, Zeng Y, Hwang, K, French SW, Lu SC, Wan YJ (2004) Mol Pharmacol 65: 550
Gladyshev VN, Factor VM, Housseau F, Hatfield DL (1998) Biochem Biophys Res Commun 251: 488
Tan M, Li S, Swaroop M, Guan K, Oberley LW, Sun Y (1999) J Biol Chem 274: 12061
Chu FF, Doroshow JH, Esworthy RS (1993) J Biol Chem 268: 2571
Brigelius-Flohé R, Kipp A (2009) Biochim Biophys Acta 1790: 1555
Florian S, Wingler K, Schmehl K, Jacobasch G, Kreuzer OJ, Meyerhof W, Brigelius-Flohé R (2001) Free Radic Res 35: 655
Chu FF, Esworthy RS (1995) Arch Biochem Biophys 323: 288
Esworthy RS, Aranda R, Martin MG, Doroshow JH, Binder SW, Chu FF (2001) Am J Physiol Gastrointest Liver Physiol 281: G848
Lee DH, Esworthy RS, Chu C, Pfeifer GP, Chu FF (2006) Cancer Res 66: 9845
Yan W, Chen X (2006) J Biol Chem 281: 7856
Chu FF, Esworthy RS, Lee L, Wilczynski S (1999) J Nutr 129: 1846
Banning A, Deubel S, Kluth D, Zhou Z, Brigelius-Flohé R (2005) Mol Cell Biol 25: 4914
Kipp A, Banning A, Brigelius-Flohé R (2007) Biol Chem 388: 1027
Takahashi K, Avissar N, Whitin J, Cohen H (1987) Arch Biochem Biophys 256: 677
Avissar N, Ornt DB, Yagil Y, Horowitz S, Watkins RH, Kerl EA, Takahashi K, Palmer IS, Cohen HJ (1994) Am J Physiol 266: C367
Yamasaki T, Tahara K, Takano S, Inoue-Murayama M, Rose MT, Minashima T, Aso H, Ito S (2006) Cell Tissue Res 326: 139
Comhair SA, Bhathena PR, Farver C, Thunnissen FB, Erzurum SC (2001) Faseb J 15: 70
Avissar N, Finkelstein JN, Horowitz S, Willey JC, Coy E, Frampton MW, Watkins RH, Khullar P, Xu YL, Cohen HJ (1996) Am J Physiol 270: L173
Burk RF (2009) Personal communication
Bierl C, Voetsch B, Jin RC, Handy DE, Loscalzo J (2004) J Biol Chem 279: 26839
Ursini F, Maiorino M, Valente M, Ferri L, Gregolin C (1982) Biochim Biophys Acta 710: 197
Schuckelt R, Brigelius-Flohé R, Maiorino M, Roveri A, Reumkens J, Strassburger W, Ursini F, Wolf B, Flohé L (1991) Free Radic Res Commun 14: 343
Arai M, Imai H, Sumi D, Imanaka T, Takano T, Chiba N, Nakagawa Y (1996) Biochem Biophys Res Commun 227: 433
Maiorino M, Scapin M, Ursini F, Biasolo M, Bosello V, Flohé L (2003) J Biol Chem 278: 34286
Moreno SG, Laux G, Brielmeier M, Bornkamm GW, Conrad M (2003) Biol Chem 384: 635
Tramer F, Vetere A, Martinelli M, Paroni F, Marsich E, Boitani C, Sandri G, Panfili E (2004) Biochem J 383: 179
Imai H, Saito M, Kirai N, Hasegawa J, Konishi K, Hattori H, Nishimura M, Naito S, Nakagawa Y (2006) J Biochem 140: 573
Pfeifer H, Conrad M, Roethlein D, Kyriakopoulos A, Brielmeier M, Bornkamm GW, Behne D (2001) Faseb J 15: 1236
Huang HS, Chen CJ, Chang WC (1999) FEBS Lett 455: 111
Hattori H, Imai H, Kirai N, Furuhama K, Sato O, Konishi K, Nakagawa Y (2007) Biochem J 408: 277
Ufer C, Wang CC, Fahling M, Schiebel H, Thiele BJ, Billett EE, Kuhn H, Borchert A (2008) Genes Dev 22: 1838
Hattori H, Imai H, Hanamoto A, Furuhama K, Nakagawa Y (2005) Biochem J 389: 279
Hattori H, Imai H, Furuhama K, Sato O, Nakagawa Y (2005) Biochem Biophys Res Commun 337: 464
Sneddon AA, Wu HC, Farquharson A, Grant I, Arthur JR, Rotondo D, Choe SN, Wahle KW (2003) Atherosclerosis 171: 57
Nam SY, Baek IJ, Lee BJ, In CH, Jung EY, Yon JM, Ahn B, Kang JK, Yu WJ, Yun YW (2003) J Reprod Dev 49: 389
Lapointe J, Kimmins S, Maclaren LA, Bilodeau JF (2005) Endocrinology 146: 2583
Roveri A, Casasco A, Maiorino M, Dalan P, Calligaro A, Ursini F (1992) J Biol Chem 267: 6142
Maiorino M, Wissing JB, Brigelius-Flohé R, Calabrese F, Roveri A, Steinert P, Ursini F, Flohé L (1998) Faseb J 12: 1359
Imai H, Hirao F, Sakamoto T, Sekine K, Mizukura Y, Saito M, Kitamoto T, Hayasaka M, Hanaoka K, Nakagawa Y (2003) Biochem Biophys Res Commun 305: 278
Conrad M, Moreno SG, Sinowatz F, Ursini F, Kolle S, Roveri A, Brielmeier M, Wurst W, Maiorino M, Bornkamm GW (2005) Mol Cell Biol 25: 7637
Schneider M, Forster H, Boersma A, Seiler A, Wehnes H, Sinowatz F, Neumuller C, Deutsch MJ, Walch A, Hrabe de Angelis M, Wurst W, Ursini F, Roveri A, Maleszewski M, Maiorino M, Conrad M (2009) Faseb J 23: 3233
Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E, Radmark O, Wurst W, Bornkamm GW, Schweizer U, Conrad M (2008) Cell Metab 8: 237
Rapoport SM, Schewe T, Wiesner R, Halangk W, Ludwig P, Janicke-Hohne M, Tannert C, Hiebsch C, Klatt D (1979) Eur J Biochem 96: 545
Foresta C, Flohé L, Garolla A, Roveri A, Ursini F, Maiorino M (2002) Biol, Reprod 67: 967
Burk RF, Olson GE, Hill KE (2007) In: Hatfield DL, Berry MJ, Gladyshev VN (eds) Selenium, Its Molecular Biology and Role in Human Health. 2nd Ed., Springer, New York: 111
Imai H, Koumura T, Nakajima R, Nomura K, Nakagawa Y (2003) Biochem J 371: 799
Nomura K, Imai H, Koumura T, Kobayashi T, Nakagawa Y (2000) Biochem J 351: 183
Brielmeier M, Bechet JM, Suppmann S, Conrad M, Laux G, Bornkamm GW (2001) Biofactors 14: 179
Brandes N, Schmitt S, Jakob U (2008) Antioxid Redox Signal 11: 997
Cook HW, Lands WE (1976) Nature 260: 630
Weitzel F, Wendel A (1993) J Biol Chem 268: 6288
Imai H, Nakagawa Y (2003) Free Radic Biol Med 34: 145
Heirman I, Ginneberge D, Brigelius-Flohé R, Hendrickx N, Agostinis P, Brouckaert P, Rottiers P, Grooten J (2006) Free Radic Biol Med 40: 285
Banning A, Brigelius-Flohé R (2005) Antioxid Redox Signal 7: 889
Wenk J, Schuller J, Hinrichs C, Syrovets T, Azoitei N, Podda M, Wlaschek M, Brenneisen P, Schneider LA, Sabiwalsky A, Peters T, Sulyok S, Dissemond J, Schauen M, Krieg T, Wirth T, Simmet T, Scharffetter-Kochanek K (2004) J Biol Chem 279: 45634
Brigelius-Flohé R, Maurer S, Lotzer K, Böl G, Kallionpaa H, Lehtolainen P, Viita H, Yla-Herttuala S (2000) Atherosclerosis 152: 307
Vernet P, Rigaudiere N, Ghyselinck N, Dufaure JP, Drevet JR (1996) Biochem Cell Biol 74: 125
Drevet JR, Lareyre JJ, Schwaab V, Vernet P, Dufaure JP (1998) Mol Reprod Dev 49: 131
Chabory E, Damon C, Lenoir A, Kauselmann G, Kern H, Zevnik B, Garrel C, Saez F, Cadet R, Henry-Berger J, Schoor M, Gottwald U, Habenicht U, Drevet JR, Vernet P (2009) J Clin Invest 119: 2074
Dear TN, Campbell K, Rabbitts TH (1991) Biochemistry 30: 10376
Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Science 300: 1439
Utomo A, Jiang X, Furuta S, Yun J, Levin DS, Wang YC, Desai KV, Green JE, Chen PL, Lee WH (2004) J Biol Chem 279: 43522
Rhee SG, Kang SW, Jeong W, Chang TS, Yang KS, Woo HA (2005) Curr Opin Cell Biol 17: 183
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2011 Zhejiang University Press, Hangzhou and Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Flohé, L. (2011). Glutathione Peroxidases. In: Selenoproteins and Mimics. Advanced Topics in Science and Technology in China. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22236-8_1
Download citation
DOI: https://doi.org/10.1007/978-3-642-22236-8_1
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-22235-1
Online ISBN: 978-3-642-22236-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)