Low-molecular-mass antioxidants in parasites

Antioxidants and Redox Signaling

Volumn 17, Issue 4, 2012, Pages 583-607

  Krauth Siegel, R Luise ^a   Leroux, Alejandro E ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; ASCORBIC ACID; CYSTEINE; GLUTATHIONE; GLUTATHIONE REDUCTASE; OVOTHIOL A; SYNTHETASE; THIOL; TRYPANOTHIONE; TRYPANOTHIONE REDUCTASE; TRYPANOTHIONE SYNTHETASE; UNCLASSIFIED DRUG;

AMINO ACID METABOLISM; AMINO ACID TRANSPORT; BIOSYNTHESIS; ENTAMOEBA; ENZYME ACTIVITY; GIARDIA; GLUTATHIONE METABOLISM; LEISHMANIA; MOLECULAR WEIGHT; NONHUMAN; OXIDATION REDUCTION REACTION; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTEIN DEPLETION; REVIEW; RNA INTERFERENCE; SCHISTOSOMA; SIGNAL TRANSDUCTION; TRICHOMONAS; TRYPANOSOMA;

ANIMALS; ANTIOXIDANTS; ASCORBIC ACID; CYSTEINE; GLUTATHIONE; MOLECULAR WEIGHT; OXIDATION-REDUCTION; PARASITES;

EID: 84860341694     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2011.4392     Document Type: Review

References (287)

1. Adak S and Datta AK. Leishmania major encodes an unusual peroxidase that is a close homologue of plant ascorbate peroxidase: a novel role of the transmembrane domain. Biochem J 390: 465-474, 2005. (Pubitemid 41337108)
2. Agorio A, Chalar C, Cardozo S, and Salinas G. Alternative mRNAs arising from trans-splicing code for mitochondrial and cytosolic variants of Echinococcus granulosus thioredoxin Glutathione reductase. J Biol Chem 278: 12920-12928, 2003. (Pubitemid 36800057)
3. Akerman SE and Müller S. 2-Cys peroxiredoxin PfTrx-Px1 is involved in the antioxidant defence of Plasmodium falciparum. Mol Biochem Parasitol 130: 75-81, 2003. (Pubitemid 37289125)
4. Alger HM and Williams DL. The disulfide redox system of Schistosoma mansoni and the importance of a multifunctional enzyme, thioredoxin glutathione reductase. Mol Biochem Parasitol 121: 129-139, 2002. (Pubitemid 34457840)
5. Alphey MS, Leonard GA, Gourley DG, Tetaud E, Fairlamb AH, and Hunter WN. The high resolution crystal structure of recombinant Crithidia fasciculata tryparedoxin-I. J Biol Chem 274: 25613-25622, 1999.
6. Alvarez MN, Peluffo G, Piacenza L, and Radi R. Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: consequences for oxidative killing and role of microbial peroxiredoxins in infectivity. J Biol Chem 286: 6627-6640, 2011.
7. Arias DG, Cabeza MS, Erben ED, Carranza PG, Lujan HD, Tellez Inon MT, Iglesias AA, and Guerrero SA. Functional characterization of methionine sulfoxide reductase A from Trypanosoma spp. Free Radic Biol Med 50: 37-46, 2011.
8. Ariyanayagam MR and Fairlamb AH. Ovothiol and trypanothione as antioxidants in trypanosomatids. Mol Biochem Parasitol 115: 189-198, 2001. (Pubitemid 32566228)
9. Ariyanayagam MR, Oza SL, Guther ML, and Fairlamb AH. Phenotypic analysis of trypanothione synthetase knockdown in the African trypanosome. Biochem J 391: 425-432, 2005. (Pubitemid 41532441)
10. Ariyanayagam MR, Oza SL, Mehlert A, and Fairlamb AH. Bis(glutathionyl) spermine and other novel trypanothione analogues in Trypanosoma cruzi. J Biol Chem 278: 27612-27619, 2003. (Pubitemid 36899947)
11. Ariza A, Vickers TJ, Greig N, Armour KA, Dixon MJ, Eggleston IM, Fairlamb AH, and Bond CS. Specificity of the trypanothione-dependent Leishmania major glyoxalase I: structure and biochemical comparison with the human enzyme. Mol Microbiol 59: 1239-1248, 2006.
12. Arrick BA, Griffith OW, and Cerami A. Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanosomiasis. J Exp Med 153: 720-725, 1981. (Pubitemid 11155805)
13. Atamna H and Ginsburg H. The malaria parasite supplies glutathione to its host cell - investigation of glutathione transport and metabolism in human erythrocytes infected with Plasmodium falciparum. Eur J Biochem 250: 670-679, 1997. (Pubitemid 28022483)
14. Azeez S, Babu RO, Aykkal R, and Narayanan R. Virtual screening and in vitro assay of potential drug like inhibitors from spices against glutathione-S-transferase of filarial nematodes. J Mol Model 2011 [Epub ahead of print]. DOI: 10.1007/s00894-011-1035-2.
15. Barker RH Jr., Liu H, Hirth B, Celatka CA, Fitzpatrick R, Xiang Y, Willert EK, Phillips MA, Kaiser M, Bacchi CJ, Rodriguez A, Yarlett N, Klinger JD, and Sybertz E. Novel Sadenosylmethionine decarboxylase inhibitors for the treatment of human African trypanosomiasis. Antimicrob Agents Chemother 53: 2052-2058, 2009.
16. Basselin M, Coombs GH, and Barrett MP. Putrescine and spermidine transport in Leishmania. Mol Biochem Parasitol 109: 37-46, 2000. (Pubitemid 30621374)
17. Becker K, Rahlfs S, Nickel C, and Schirmer RH. Glutathione - functions and metabolism in the malarial parasite Plasmodium falciparum. Biol Chem 384: 551-566, 2003. (Pubitemid 36609171)
18. Bennuru S, Semnani R, Meng Z, Ribeiro JM, Veenstra TD, and Nutman TB. Brugia malayi excreted/secreted proteins at the host/parasite interface: stage- and gender-specific proteomic profiling. PLoS Negl Trop Dis 3: e410, 2009.
19. Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE, Haas B, Bohme U, Hannick L, Aslett MA, Shallom J, Marcello L, Hou L, Wickstead B, Alsmark UC, Arrowsmith C, Atkin RJ, Barron AJ, Bringaud F, Brooks K, Carrington M, Cherevach I, Chillingworth TJ, Churcher C, Clark LN, Corton CH, Cronin A, Davies RM, Doggett J, Djikeng A, Feldblyum T, Field MC, Fraser A, Goodhead I, Hance Z, Harper D, Harris BR, Hauser H, Hostetler J, Ivens A, Jagels K, Johnson D, Johnson J, Jones K, Kerhornou AX, Koo H, Larke N, Landfear S, Larkin C, Leech V, Line A, Lord A, Macleod A, Mooney PJ, Moule S, Martin DM, Morgan GW, Mungall K, Norbertczak H, Ormond D, Pai G, Peacock CS, Peterson J, Quail MA, Rabbinowitsch E, Rajandream MA, Reitter C, Salzberg SL, Sanders M, Schobel S, Sharp S, Simmonds M, Simpson AJ, Tallon L, Turner CM, Tait A, Tivey AR, Van Aken S, Walker D, Wanless D, Wang S, White B, White O, Whitehead S, Woodward J, Wortman J, Adams MD, Embley TM, Gull K, Ullu E, Barry JD, Fairlamb AH, Opperdoes F, Barrell BG, Donelson JE, Hall N, Fraser CM, Melville SE, and El-Sayed NM. The genome of the African trypanosome Trypanosoma brucei. Science 309: 416-422, 2005.
20. Beswick TC, Willert EK, and Phillips MA. Mechanisms of allosteric regulation of Trypanosoma cruzi S-adenosylmethionine decarboxylase. Biochemistry 45: 7797-7807, 2006. (Pubitemid 44185496)
21. Bhattacharya J and Swarup-Mitra S. Reduction in erythrocytic GSH level and stability in Plasmodium vivax malaria. Trans R Soc Trop Med Hyg 81: 64-66, 1987.
22. Bitonti AJ, Byers TL, Bush TL, Casara PJ, Bacchi CJ, Clarkson AB Jr., McCann PP, and Sjoerdsma A. Cure of Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense infections in mice with an irreversible inhibitor of Sadenosylmethionine decarboxylase. Antimicrob Agents Chemother 34: 1485-1490, 1990. (Pubitemid 20257593)
23. Bitonti AJ, Dumont JA, and McCann PP. Characterization of Trypanosoma brucei brucei S-adenosyl-L-methionine decarboxylase and its inhibition by Berenil, pentamidine and methylglyoxal bis(guanylhydrazone). Biochem J 237: 685-689, 1986. (Pubitemid 16003770)
24. Bitonti AJ, Kelly SE, and McCann PP. Characterization of spermidine synthase from Trypanosoma brucei brucei. Mol Biochem Parasitol 13: 21-28, 1984. (Pubitemid 14024944)
25. Bocedi A, Dawood KF, Fabrini R, Federici G, Gradoni L, Pedersen JZ, and Ricci G. Trypanothione efficiently intercepts nitric oxide as a harmless iron complex in trypanosomatid parasites. FASEB J 24: 1035-1042, 2010.
26. Boitz JM, Yates PA, Kline C, Gaur U, Wilson ME, Ullman B, and Roberts SC. Leishmania donovani ornithine decarboxylase is indispensable for parasite survival in the mammalian host. Infect Immun 77: 756-763, 2009.
27. Bollinger JM Jr., Kwon DS, Huisman GW, Kolter R, and Walsh CT. Glutathionylspermidine metabolism in Escherichia coli. Purification, cloning, overproduction, and characterization of a bifunctional glutathionylspermidine synthetase/amidase. J Biol Chem 270: 14031-14041, 1995.
28. Bonilla M, Denicola A, Novoselov SV, Turanov AA, Protasio A, Izmendi D, Gladyshev VN, and Salinas G. Platyhelminth mitochondrial and cytosolic redox homeostasis is controlled by a single thioredoxin glutathione reductase and dependent on selenium and glutathione. J Biol Chem 283: 17898-17907, 2008.
29. Braunshausen A and Seebeck FP. Identification and characterization of the first ovothiol biosynthetic enzyme. J Am Chem Soc 133: 1757-1759, 2011.
30. Brown DM, Upcroft JA, and Upcroft P. Cysteine is the major low-molecular weight thiol in Giardia duodenalis. Mol Biochem Parasitol 61: 155-158, 1993.
31. Brown DM, Upcroft JA, and Upcroft P. A thioredoxin reductase-class of disulphide reductase in the protozoan parasite Giardia duodenalis. Mol Biochem Parasitol 83: 211- 220, 1996.
32. Bruchhaus I, Richter S, and Tannich E. Recombinant expression and biochemical characterization of an NADPH:flavin oxidoreductase from Entamoeba histolytica. Biochem J 330 (Pt 3): 1217-1221, 1998.
33. Buchholz K, Putrianti ED, Rahlfs S, Schirmer RH, Becker K, and Matuschewski K. Molecular genetics evidence for the in vivo roles of the two major NADPH-dependent disulfide reductases in the malaria parasite. J Biol Chem 285: 37388-37395, 2010.
34. Budde H, Flohé L, Hecht HJ, Hofmann B, Stehr M, Wissing J, and Lunsdorf H. Kinetics and redox-sensitive oligomerisation reveal negative subunit cooperativity in tryparedoxin peroxidase of Trypanosoma brucei brucei. Biol Chem 384: 619-633, 2003. (Pubitemid 36609177)
35. Camargo EP, Coelho JA, Moraes G, and Figueiredo EN. Trypanosoma spp., Leishmania spp. and Leptomonas spp.: enzymes of ornithine-arginine metabolism. Exp Parasitol 46: 141-144, 1978. (Pubitemid 9090528)
36. Canepa GE, Bouvier LA, Miranda MR, Uttaro AD, and Pereira CA. Characterization of Trypanosoma cruzi L-cysteine transport mechanisms and their adaptive regulation. FEMS Microbiol Lett 292: 27-32, 2009.
37. Carnieri EG, Moreno SN, and Docampo R. Trypanothione-dependent peroxide metabolism in Trypanosoma cruzi different stages. Mol Biochem Parasitol 61: 79-86, 1993.
38. Carrillo C, Canepa GE, Algranati ID, and Pereira CA. Molecular and functional characterization of a spermidine transporter (TcPAT12) from Trypanosoma cruzi. Biochem Biophys Res Commun 344: 936-940, 2006.
39. Carrillo C, Cejas S, Gonzalez NS, and Algranati ID. Trypanosoma cruzi epimastigotes lack ornithine decarboxylase but can express a foreign gene encoding this enzyme. FEBS Lett 454: 192-196, 1999. (Pubitemid 29304598)
40. Castro H, Budde H, Flohé L, Hofmann B, Lunsdorf H, Wissing J, and Tomás AM. Specificity and kinetics of a mitochondrial peroxiredoxin of Leishmania infantum. Free Radic Biol Med 33: 1563-1574, 2002. (Pubitemid 35351600)
41. Castro H, Romao S, Carvalho S, Teixeira F, Sousa C, and Tomás AM. Mitochondrial redox metabolism in trypanosomatids is independent of tryparedoxin activity. PLoS One 5: e12607, 2010.
42. Castro H, Sousa C, Novais M, Santos M, Budde H, Cordeiro-da-Silva A, Flohé L, and Tomás AM. Two linked genes of Leishmania infantum encode tryparedoxins localised to cytosol and mitochondrion. Mol Biochem Parasitol 136: 137-147, 2004. (Pubitemid 38757982)
43. Castro H, Sousa C, Santos M, Cordeiro-da-Silva A, Flohé L, and Tomás AM. Complementary antioxidant defense by cytoplasmic and mitochondrial peroxiredoxins in Leishmania infantum. Free Radic Biol Med 33: 1552-1562, 2002. (Pubitemid 35351599)
44. Castro H, Teixeira F, Romao S, Santos M, Cruz T, Flórido M, Appelberg R, Oliveira P, Ferreira-da-Silva F, and Tomás AM. Leishmania mitochondrial peroxiredoxin plays a crucial peroxidase-unrelated role during infection: insight into its novel chaperone activity. PLoS Pathog 7: e1002325, 2011.
45. Castro H and Tomás AM. Peroxidases of trypanosomatids. Antioxid Redox Signal 10: 1593-1606, 2008. (Pubitemid 351934269)
46. Ceylan S, Seidel V, Ziebart N, Berndt C, Dirdjaja N, and Krauth-Siegel RL. The dithiol glutaredoxins of African trypanosomes have distinct roles and are closely linked to the unique trypanothione metabolism. J Biol Chem 285: 35224-35237, 2010.
47. Clark D, Albrecht M, and Arevalo J. Ascorbate variations and dehydroascorbate reductase activity in Trypanosoma cruzi epimastigotes and trypomastigotes. Mol Biochem Parasitol 66: 143-145, 1994. (Pubitemid 24250062)
48. Cobbold SA, Martin RE, and Kirk K. Methionine transport in the malaria parasite Plasmodium falciparum. Int J Parasitol 41: 125-135, 2011.
49. Comini M, Menge U, Wissing J, and Flohé L. Trypanothione synthesis in crithidia revisited. J Biol Chem 280: 6850-6860, 2005. (Pubitemid 40341240)
50. Comini MA, Guerrero SA, Haile S, Menge U, Lunsdorf H, and Flohé L. Validation of Trypanosoma brucei trypanothione synthetase as drug target. Free Radic Biol Med 36: 1289-1302, 2004. (Pubitemid 38526323)
51. Comini MA, Krauth-Siegel RL, and Flohé L. Depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in African trypanosomes. Biochem J 402: 43-49, 2007.
52. Comini MA, Rettig J, Dirdjaja N, Hanschmann EM, Berndt C, and Krauth-Siegel RL. Monothiol glutaredoxin-1 is an essential iron-sulfur protein in the mitochondrion of African trypanosomes. J Biol Chem 283: 27785-27798, 2008.
53. Cookson E, Blaxter ML, and Selkirk ME. Identification of the major soluble cuticular glycoprotein of lymphatic filarial nematode parasites (gp29) as a secretory homolog of glutathione peroxidase. Proc Natl Acad Sci U S A 89: 5837- 5841, 1992.
54. Coombs GH, Westrop GD, Suchan P, Puzova G, Hirt RP, Embley TM, Mottram JC, and Müller S. The amitochondriate eukaryote Trichomonas vaginalis contains a divergent thioredoxin-linked peroxiredoxin antioxidant system. J Biol Chem 279: 5249-5256, 2004. (Pubitemid 38220544)
55. Cruz F and Ferry JG. Interaction of iron-sulfur flavoprotein with oxygen and hydrogen peroxide. Biochim Biophys Acta 1760: 858-864, 2006. (Pubitemid 43816182)
56. Cunningham ML and Fairlamb AH. Trypanothione reductase from Leishmania donovani. Purification, characterisation and inhibition by trivalent antimonials. Eur J Biochem 230: 460-468, 1995.
57. da Silva ER, da Silva MF, Fischer H, Mortara RA, Mayer MG, Framesqui K, Silber AM, and Floeter-Winter LM. Biochemical and biophysical properties of a highly active recombinant arginase from Leishmania (Leishmania) amazonensis and subcellular localization of native enzyme. Mol Biochem Parasitol 159: 104-111, 2008. (Pubitemid 351621903)
58. Dalle-Donne I, Milzani A, Gagliano N, Colombo R, Giustarini D, and Rossi R. Molecular mechanisms and potential clinical significance of S-glutathionylation. Antioxid Redox Signal 10: 445-473, 2008.
59. Deponte M, Rahlfs S, and Becker K. Peroxiredoxin systems of protozoal parasites. Subcell Biochem 44: 219-229, 2007.
60. 2-scavenging flavodiiron protein in the human parasite Giardia intestinalis. J Biol Chem 283: 4061-4068, 2008.
61. Diechtierow M and Krauth-Siegel RL. A tryparedoxin-dependent peroxidase protects African trypanosomes from membrane damage. Free Radic Biol Med 51: 856-868, 2011.
62. Dolai S, Yadav RK, Pal S, and Adak S. Leishmania major ascorbate peroxidase overexpression protects cells against reactive oxygen species-mediated cardiolipin oxidation. Free Radic Biol Med 45: 1520-1529, 2008.
63. Dolai S, Yadav RK, Pal S, and Adak S. Overexpression of mitochondrial Leishmania major ascorbate peroxidase enhances tolerance to oxidative stress-induced programmed cell death and protein damage. Eukaryot Cell 8: 1721-1731, 2009.
64. Dormeyer M, Reckenfelderbaumer N, Lüdemann H, and Krauth-Siegel RL. Trypanothione-dependent synthesis of deoxyribonucleotides by Trypanosoma brucei ribonucleotide reductase. J Biol Chem 276: 10602-10606, 2001. (Pubitemid 38094248)
65. Drummelsmith J, Girard I, Trudel N, and Ouellette M. Differential protein expression analysis of Leishmania major reveals novel roles for methionine adenosyltransferase and S-adenosylmethionine in methotrexate resistance. J Biol Chem 279: 33273-33280, 2004. (Pubitemid 39062974)
66. Dumas C, Ouellette M, Tovar J, Cunningham ML, Fairlamb AH, Tamar S, Olivier M, and Papadopoulou B. Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages. EMBO J 16: 2590-2598, 1997. (Pubitemid 27226198)
67. Duszenko M, Muhlstadt K, and Broder A. Cysteine is an essential growth factor for Trypanosoma brucei bloodstream forms. Mol Biochem Parasitol 50: 269-273, 1992.
68. Eckman JR and Eaton JW. Dependence of plasmodial glutathione metabolism on the host cell. Nature 278: 754-756, 1979. (Pubitemid 9160284)
69. Ekstrom JL, Tolbert WD, Xiong H, Pegg AE, and Ealick SE. Structure of a human S-adenosylmethionine decarboxylase self-processing ester intermediate and mechanism of putrescine stimulation of processing as revealed by the H243A mutant. Biochemistry 40: 9495- 9504, 2001.
70. El-Sayed NM, Myler PJ, Bartholomeu DC, Nilsson D, Aggarwal G, Tran AN, Ghedin E, Worthey EA, Delcher AL, Blandin G, Westenberger SJ, Caler E, Cerqueira GC, Branche C, Haas B, Anupama A, Arner E, Aslund L, Attipoe P, Bontempi E, Bringaud F, Burton P, Cadag E, Campbell DA, Carrington M, Crabtree J, Darban H, da Silveira JF, de Jong P, Edwards K, Englund PT, Fazelina G, Feldblyum T, Ferella M, Frasch AC, Gull K, Horn D, Hou L, Huang Y, Kindlund E, Klingbeil M, Kluge S, Koo H, Lacerda D, Levin MJ, Lorenzi H, Louie T, Machado CR, McCulloch R, McKenna A, Mizuno Y, Mottram JC, Nelson S, Ochaya S, Osoegawa K, Pai G, Parsons M, Pentony M, Pettersson U, Pop M, Ramirez JL, Rinta J, Robertson L, Salzberg SL, Sanchez DO, Seyler A, Sharma R, Shetty J, Simpson AJ, Sisk E, Tammi MT, Tarleton R, Teixeira S, Van Aken S, Vogt C, Ward PN, Wickstead B, Wortman J, White O, Fraser CM, Stuart KD, and Andersson B. The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 309: 409-415, 2005.
71. Fahey RC, Newton GL, Arrick B, Overdank-Bogart T, and Aley SB. Entamoeba histolytica: a eukaryote without glutathione metabolism. Science 224: 70-72, 1984. (Pubitemid 14171643)
72. Fairlamb AH, Blackburn P, Ulrich P, Chait BT, and Cerami A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 227: 1485-1487, 1985. (Pubitemid 15146992)
73. Fairlamb AH and Cerami A. Metabolism and functions of trypanothione in the Kinetoplastida. Annu Rev Microbiol 46: 695-729, 1992.
74. Färber PM, Becker K, Müller S, Schirmer RH, and Franklin RM. Molecular cloning and characterization of a putative glutathione reductase gene, the PfGR2 gene, from Plasmodium falciparum. Eur J Biochem 239: 655-661, 1996. (Pubitemid 26253037)
75. Filser M, Comini MA, Molina-Navarro MM, Dirdjaja N, Herrero E, and Krauth-Siegel RL. Cloning, functional analysis, and mitochondrial localization of Trypanosoma brucei monothiol glutaredoxin-1. Biol Chem 389: 21-32, 2008. (Pubitemid 350308201)
76. Flohé L, Budde H, Bruns K, Castro H, Clos J, Hofmann B, Kansal-Kalavar S, Krumme D, Menge U, Plank-Schumacher K, Sztajer H, Wissing J, Wylegalla C, and Hecht HJ. Tryparedoxin peroxidase of Leishmania donovani: molecular cloning, heterologous expression, specificity, and catalytic mechanism. Arch Biochem Biophys 397: 324-335, 2002. (Pubitemid 34852299)
77. Flohé L, Hecht HJ, and Steinert P. Glutathione and trypanothione in parasitic hydroperoxide metabolism. Free Radic Biol Med 27: 966-984, 1999. (Pubitemid 29507470)
78. Francis SE, Sullivan DJ Jr., and Goldberg DE. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu Rev Microbiol 51: 97-123, 1997. (Pubitemid 27433044)
79. Fritz-Wolf K, Becker A, Rahlfs S, Harwaldt P, Schirmer RH, Kabsch W, and Becker K. X-ray structure of glutathione Stransferase from the malarial parasite Plasmodium falciparum. Proc Natl Acad Sci U S A 100: 13821-13826, 2003. (Pubitemid 37499150)
80. Fyfe PK, Alphey MS, and Hunter WN. Structure of Trypanosoma brucei glutathione synthetase: domain and loop alterations in the catalytic cycle of a highly conserved enzyme. Mol Biochem Parasitol 170: 93-99, 2010.
81. Fyfe PK, Oza SL, Fairlamb AH, and Hunter WN. Leishmania trypanothione synthetase-amidase structure reveals a basis for regulation of conflicting synthetic and hydrolytic activities. J Biol Chem 283: 17672-17680, 2008.
82. Gaur U, Roberts SC, Dalvi RP, Corraliza I, Ullman B, and Wilson ME. An effect of parasite-encoded arginase on the outcome of murine cutaneous leishmaniasis. J Immunol 179: 8446-8453, 2007.
83. Ghoda L, Phillips MA, Bass KE, Wang CC, and Coffino P. Trypanosome ornithine decarboxylase is stable because it lacks sequences found in the carboxyl terminus of the mouse enzyme which target the latter for intracellular degradation. J Biol Chem 265: 11823-11826, 1990. (Pubitemid 20219354)
84. Ghoda L, van Daalen Wetters T, Macrae M, Ascherman D, and Coffino P. Prevention of rapid intracellular degradation of ODC by a carboxyl-terminal truncation. Science 243: 1493-1495, 1989. (Pubitemid 19087139)
85. Gilbert HF. Molecular and cellular aspects of thiol-disulfide exchange. Adv Enzymol Relat Areas Mol Biol 63: 69-172, 1990.
86. Gillin FD and Diamond LS. Attachment of Entamoeba histolytica to glass in a defined maintenance medium: specific requirement for cysteine and ascorbic acid. J Protozool 27: 474-478, 1980. (Pubitemid 11097626)
87. Gilroy C, Olenyik T, Roberts SC, and Ullman B. Spermidine synthase is required for virulence of Leishmania donovani. Infect Immun 79: 2764-2769, 2011.
88. Gommel DU, Nogoceke E, Morr M, Kiess M, Kalisz HM, and Flohé L. Catalytic characteristics of tryparedoxin. Eur J Biochem 248: 913-918, 1997. (Pubitemid 27400049)
89. Gonzalez NS, Ceriani C, and Algranati ID. Differential regulation of putrescine uptake in Trypanosoma cruzi and other trypanosomatids. Biochem Biophys Res Commun 188: 120-128, 1992.
90. Greig N, Wyllie S, Vickers TJ, and Fairlamb AH. Trypanothione- dependent glyoxalase I in Trypanosoma cruzi. Biochem J 400: 217-223, 2006. (Pubitemid 44852035)
91. Grondin K, Haimeur A, Mukhopadhyay R, Rosen BP, and Ouellette M. Co-amplification of the gamma-glutamylcysteine synthetase gene gsh1 and of the ABC transporter gene pgpA in arsenite-resistant Leishmania tarentolae. EMBO J 16: 3057-3065, 1997. (Pubitemid 27234945)
92. Guevara-Flores A, Del Arenal IP, Mendoza-Hernandez G, Pardo JP, Flores-Herrera O, and Rendon JL. Mitochondrial thioredoxin-glutathione reductase from larval Taenia crassiceps (Cysticerci). J Parasitol Res 2010: pii 719856, 2010.
93. Guimond C, Trudel N, Brochu C, Marquis N, El Fadili A, Peytavi R, Briand G, Richard D, Messier N, Papadopoulou B, Corbeil J, Bergeron MG, Legare D, and Ouellette M. Modulation of gene expression in Leishmania drug resistant mutants as determined by targeted DNA microarrays. Nucleic Acids Res 31: 5886-5896, 2003. (Pubitemid 37442315)
94. Hanson S, Adelman J, and Ullman B. Amplification and molecular cloning of the ornithine decarboxylase gene of Leishmania donovani. J Biol Chem 267: 2350-2559, 1992.
95. Hasne MP and Ullman B. Identification and characterization of a polyamine permease from the protozoan parasite Leishmania major. J Biol Chem 280: 15188-15194, 2005. (Pubitemid 40562874)
96. Henderson GB, Fairlamb AH, and Cerami A. Trypanothione dependent peroxide metabolism in Crithidia fasciculata and Trypanosoma brucei. Mol Biochem Parasitol 24: 39-45, 1987. (Pubitemid 17067030)
97. Henderson GB, Yamaguchi M, Novoa L, Fairlamb AH, and Cerami A. Biosynthesis of the trypanosomatid metabolite trypanothione: purification and characterization of trypanothione synthetase from Crithidia fasciculata. Biochemistry 29: 3924-3929, 1990.
98. Herbas MS and Suzuki H. Vitamin C deficiency fails to protect mice from malaria. Exp Anim 59: 239-243, 2010.
99. Hewitson JP, Harcus YM, Curwen RS, Dowle AA, Atmadja AK, Ashton PD, Wilson A, and Maizels RM. The secretome of the filarial parasite, Brugia malayi: proteomic profile of adult excretory-secretory products. Mol Biochem Parasitol 160: 8-21, 2008. (Pubitemid 351694354)
100. Hillebrand H, Schmidt A, and Krauth-Siegel RL. A second class of peroxidases linked to the trypanothione metabolism. J Biol Chem 278: 6809-6815, 2003. (Pubitemid 36800670)
101. Hiller N, Fritz-Wolf K, Deponte M, Wende W, Zimmermann H, and Becker K. Plasmodium falciparum glutathione S-transferase-structural and mechanistic studies on ligand binding and enzyme inhibition. Protein Sci 15: 281-289, 2006. (Pubitemid 43145000)
102. Hofmann B, Budde H, Bruns K, Guerrero SA, Kalisz HM, Menge U, Montemartini M, Nogoceke E, Steinert P, Wissing JB, Flohé L, and Hecht HJ. Structures of tryparedoxins revealing interaction with trypanothione. Biol Chem 382: 459-471, 2001. (Pubitemid 32372490)
103. Hunter KJ, Le Quesne SA, and Fairlamb AH. Identification and biosynthesis of N1,N9-bis(glutathionyl)aminopropylcadaverine (homotrypanothione) in Trypanosoma cruzi. Eur J Biochem 226: 1019-1027, 1994.
104. Husain A, Jeelani G, Sato D, and Nozaki T. Global analysis of gene expression in response to L-Cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica. BMC Genomics 12: 275, 2011.
105. Husain A, Sato D, Jeelani G, Mi-ichi F, Ali V, Suematsu M, Soga T, and Nozaki T. Metabolome analysis revealed increase in S-methylcysteine and phosphatidylisopropanolamine synthesis upon L-cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica. J Biol Chem 285: 39160-39170, 2010.
106. Hussain S, Ali V, Jeelani G, and Nozaki T. Isoformdependent feedback regulation of serine O-acetyltransferase isoenzymes involved in L-cysteine biosynthesis of Entamoeba histolytica. Mol Biochem Parasitol 163: 39-47, 2009.
107. Huynh TT, Huynh VT, Harmon MA, and Phillips MA. Gene knockdown of gamma-glutamylcysteine synthetase by RNAi in the parasitic protozoa Trypanosoma brucei demonstrates that it is an essential enzyme. J Biol Chem 278: 39794-39800, 2003. (Pubitemid 37248541)
108. Iheanacho EN, Stocker R, and Hunt NH. Redox metabolism of vitamin C in blood of normal and malaria-infected mice. Biochim Biophys Acta 1182: 15-21, 1993. (Pubitemid 23233668)
109. Irsch T and Krauth-Siegel RL. Glyoxalase II of African trypanosomes is trypanothione-dependent. J Biol Chem 279: 22209-22217, 2004. (Pubitemid 38679416)
110. Ivens AC, Peacock CS, Worthey EA, Murphy L, Aggarwal G, Berriman M, Sisk E, Rajandream MA, Adlem E, Aert R, Anupama A, Apostolou Z, Attipoe P, Bason N, Bauser C, Beck A, Beverley SM, Bianchettin G, Borzym K, Bothe G, Bruschi CV, Collins M, Cadag E, Ciarloni L, Clayton C, Coulson RM, Cronin A, Cruz AK, Davies RM, De Gaudenzi J, Dobson DE, Duesterhoeft A, Fazelina G, Fosker N, Frasch AC, Fraser A, Fuchs M, Gabel C, Goble A, Goffeau A, Harris D, Hertz-Fowler C, Hilbert H, Horn D, Huang Y, Klages S, Knights A, Kube M, Larke N, Litvin L, Lord A, Louie T, Marra M, Masuy D, Matthews K, Michaeli S, Mottram JC, Muller-Auer S, Munden H, Nelson S, Norbertczak H, Oliver K, O'Neil S, Pentony M, Pohl TM, Price C, Purnelle B, Quail MA, Rabbinowitsch E, Reinhardt R, Rieger M, Rinta J, Robben J, Robertson L, Ruiz JC, Rutter S, Saunders D, Schafer M, Schein J, Schwartz DC, Seeger K, Seyler A, Sharp S, Shin H, Sivam D, Squares R, Squares S, Tosato V, Vogt C, Volckaert G, Wambutt R, Warren T, Wedler H, Woodward J, Zhou S, Zimmermann W, Smith DF, Blackwell JM, Stuart KD, Barrell B, and Myler PJ. The genome of the kinetoplastid parasite, Leishmania major. Science 309: 436-442, 2005.
111. Jaeger T and Flohé L. The thiol-based redox networks of pathogens: unexploited targets in the search for new drugs. Biofactors 27: 109-120, 2006. (Pubitemid 44444593)
112. Jeelani G, Husain A, Sato D, Ali V, Suematsu M, Soga T, and Nozaki T. Two atypical L-cysteine-regulated NADPHdependent oxidoreductases involved in redox maintenance, L-cystine and iron reduction, and metronidazole activation in the enteric protozoan Entamoeba histolytica. J Biol Chem 285: 26889-26899, 2010.
113. Jiang Y, Roberts SC, Jardim A, Carter NS, Shih S, Ariyanayagam M, Fairlamb AH, and Ullman B. Ornithine decarboxylase gene deletion mutants of Leishmania donovani. J Biol Chem 274: 3781-3788, 1999. (Pubitemid 29077226)
114. Jocelyn PC. The standard redox potential of cysteinecystine from the thiol-disulphide exchange reaction with glutathione and lipoic acid. Eur J Biochem 2: 327-331, 1967.
115. Jones DC, Ariza A, Chow WH, Oza SL, and Fairlamb AH. Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi. Mol Biochem Parasitol 169: 12-19, 2010.
116. Kandpal M and Tekwani BL. Polyamine transport systems of Leishmania donovani promastigotes. Life Sci 60: 1793-1801, 1997. (Pubitemid 27225909)
117. Kanzok SM, Schirmer RH, Turbachova I, Iozef R, and Becker K. The thioredoxin system of the malaria parasite Plasmodium falciparum. Glutathione reduction revisited. J Biol Chem 275: 40180-40186, 2000. (Pubitemid 32064647)
118. Kawazu S, Komaki K, Tsuji N, Kawai S, Ikenoue N, Hatabu T, Ishikawa H, Matsumoto Y, Himeno K, and Kano S. Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum. Mol Biochem Parasitol 116: 73-79, 2001. (Pubitemid 32706428)
119. Kehr S, Jortzik E, Delahunty C, Yates JR, Rahlfs S, and Becker K. Protein S-glutathionylation in malaria parasites. Antioxid Redox Signal 15: 2855-2865, 2011.
120. Kehr S, Sturm N, Rahlfs S, Przyborski JM, and Becker K. Compartmentation of redox metabolism in malaria parasites. PLoS Pathog 6: e1001242, 2010.
121. Kinch LN, Scott JR, Ullman B, and Phillips MA. Cloning and kinetic characterization of the Trypanosoma cruzi Sadenosylmethionine decarboxylase. Mol Biochem Parasitol 101: 1-11, 1999. (Pubitemid 29257836)
122. Komaki-Yasuda K, Kawazu S, and Kano S. Disruption of the Plasmodium falciparum 2-Cys peroxiredoxin gene renders parasites hypersensitive to reactive oxygen and nitrogen species. FEBS Lett 547: 140-144, 2003. (Pubitemid 36829394)
123. König J and Fairlamb AH. A comparative study of type I and type II tryparedoxin peroxidases in Leishmania major. FEBS J 274: 5643-5658, 2007. (Pubitemid 47622078)
124. Krauth-Siegel LR, Comini MA, and Schlecker T. The trypanothione system. Subcell Biochem 44: 231-251, 2007.
125. Krauth-Siegel RL, Bauer H, and Schirmer RH. Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new drug targets in trypanosomes and malaria-causing plasmodia. Angew Chem Int Ed Engl 44: 690-715, 2005. (Pubitemid 40203977)
126. Krauth-Siegel RL and Comini MA. Redox control in trypanosomatids, parasitic protozoa with trypanothionebased thiol metabolism. Biochim Biophys Acta 1780: 1236- 1248, 2008.
127. Krauth-Siegel RL, Enders B, Henderson GB, Fairlamb AH, and Schirmer RH. Trypanothione reductase from Trypanosoma cruzi. Purification and characterization of the crystalline enzyme. Eur J Biochem 164: 123-128, 1987. (Pubitemid 17053675)
128. Krauth-Siegel RL and Lüdemann H. Reduction of dehydroascorbate by trypanothione. Mol Biochem Parasitol 80: 203-208, 1996. (Pubitemid 26313383)
129. Krauth-Siegel RL, Müller JG, Lottspeich F, and Schirmer RH. Glutathione reductase and glutamate dehydrogenase of Plasmodium falciparum, the causative agent of tropical malaria. Eur J Biochem 235: 345-350, 1996. (Pubitemid 26045450)
130. Krauth-Siegel RL and Schöneck R. Flavoprotein structure and mechanism. 5. Trypanothione reductase and lipoamide dehydrogenase as targets for a structure-based drug design. FASEB J 9: 1138-1146, 1995.
131. Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, Krauth-Siegel RL, and Clayton C. Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Mol Microbiol 35: 542-552, 2000. (Pubitemid 30085272)
132. Krnajski Z, Walter RD, and Müller S. Isolation and functional analysis of two thioredoxin peroxidases (peroxiredoxins) from Plasmodium falciparum. Mol Biochem Parasitol 113: 303-308, 2001. (Pubitemid 32274303)
133. Kudryashova EV, Leferink NG, Slot IG, and van Berkel WJ. Galactonolactone
134. Kumar B, Chaubey S, Shah P, Tanveer A, Charan M, Siddiqi MI, and Habib S. Interaction between sulphur mobilisation proteins SufB and SufC: evidence for an ironsulphur cluster biogenesis pathway in the apicoplast of Plasmodium falciparum. Int J Parasitol 41: 991-999, 2011.
135. Kumar C, Igbaria A, D'Autreaux B, Planson AG, Junot C, Godat E, Bachhawat AK, Delaunay-Moisan A, and Toledano MB. Glutathione revisited: a vital function in iron metabolism and ancillary role in thiol-redox control. EMBO J 30: 2044-2056, 2011.
136. Kunchithapautham K, Padmavathi B, Narayanan RB, Kaliraj P, and Scott AL. Thioredoxin from Brugia malayi: defining a 16-kilodalton class of thioredoxins from nematodes. Infect Immun 71: 4119-4126, 2003. (Pubitemid 36753741)
137. Kuntz AN, Davioud-Charvet E, Sayed AA, Califf LL, Dessolin J, Arner ES, and Williams DL. Thioredoxin glutathione reductase from Schistosoma mansoni: an essential parasite enzyme and a key drug target. PLoS Med 4: e206, 2007.
138. Le Quesne SA and Fairlamb AH. Regulation of a highaffinity diamine transport system in Trypanosoma cruzi epimastigotes. Biochem J 316 (Pt 2): 481-486, 1996. (Pubitemid 26182145)
139. Leitsch D, Kolarich D, Binder M, Stadlmann J, Altmann F, and Duchene M. Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. Mol Microbiol 72: 518-536, 2009.
140. Li F, Hua SB, Wang CC, and Gottesdiener KM. Procyclic Trypanosoma brucei cell lines deficient in ornithine decarboxylase activity. Mol Biochem Parasitol 78: 227-236, 1996. (Pubitemid 26201620)
141. Liebau E, Dawood KF, Fabrini R, Fischer-Riepe L, Perbandt M, Stella L, Pedersen JZ, Bocedi A, Petrarca P, Federici G, and Ricci G. Tetramerization and cooperativity in Plasmodium falciparum glutathione S-transferase are mediated by atypic loop 113-119. J Biol Chem 284: 22133-22139, 2009.
142. Liebau E, De Maria F, Burmeister C, Perbandt M, Turella P, Antonini G, Federici G, Giansanti F, Stella L, Lo Bello M, Caccuri AM, and Ricci G. Cooperativity and pseudo-cooperativity in the glutathione S-transferase from Plasmodium falciparum. J Biol Chem 280: 26121-26128, 2005. (Pubitemid 41022206)
143. Lill R and Muhlenhoff U. Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases. Annu Rev Biochem 77: 669-700, 2008.
144. Lin YC, Hsu JY, Chiang SC, and Lee ST. Distinct overexpression of cytosolic and mitochondrial tryparedoxin peroxidases results in preferential detoxification of different oxidants in arsenite-resistant Leishmania amazonensis with and without DNA amplification. Mol Biochem Parasitol 142: 66-75, 2005. (Pubitemid 40720129)
145. Lindley H. A study of the kinetics of the reaction between thiol compounds and choloracetamide. Biochem J 74: 577- 584, 1960.
146. Loftus B, Anderson I, Davies R, Alsmark UC, Samuelson J, Amedeo P, Roncaglia P, Berriman M, Hirt RP, Mann BJ, Nozaki T, Suh B, Pop M, Duchene M, Ackers J, Tannich E, Leippe M, Hofer M, Bruchhaus I, Willhoeft U, Bhattacharya A, Chillingworth T, Churcher C, Hance Z, Harris B, Harris D, Jagels K, Moule S, Mungall K, Ormond D, Squares R, Whitehead S, Quail MA, Rabbinowitsch E, Norbertczak H, Price C, Wang Z, Guillen N, Gilchrist C, Stroup SE, Bhattacharya S, Lohia A, Foster PG, Sicheritz-Ponten T, Weber C, Singh U, Mukherjee C, El-Sayed NM, Petri WA, Jr., Clark CG, Embley TM, Barrell B, Fraser CM, and Hall N. The genome of the protist parasite Entamoeba histolytica. Nature 433: 865-868, 2005. (Pubitemid 40314894)
147. Logan FJ, Taylor MC, Wilkinson SR, Kaur H, and Kelly JM. The terminal step in vitamin C biosynthesis in Trypanosoma cruzi is mediated by a FMN-dependent galactonolactone oxidase. Biochem J 407: 419-426, 2007. (Pubitemid 350058475)
148. Lopez JA, Carvalho TU, de Souza W, Flohé L, Guerrero SA, Montemartini M, Kalisz HM, Nogoceke E, Singh M, Alves MJ, and Colli W. Evidence for a trypanothione-dependent peroxidase system in Trypanosoma cruzi. Free Radic Biol Med 28: 767-772, 2000. (Pubitemid 30171290)
149. Lüdemann H, Dormeyer M, Sticherling C, Stallmann D, Follmann H, and Krauth-Siegel RL. Trypanosoma brucei tryparedoxin, a thioredoxin-like protein in African trypanosomes. FEBS Lett 431: 381-385, 1998. (Pubitemid 28352394)
150. Lueder DV and Phillips MA. Characterization of Trypanosoma brucei gamma-glutamylcysteine synthetase, an essential enzyme in the biosynthesis of trypanothione (diglutathionylspermidine). J Biol Chem 271: 17485-17490, 1996. (Pubitemid 26244315)
151. Lüersen K, Müller S, Hussein A, Liebau E, and Walter RD. The gamma-glutamylcysteine synthetase of Onchocerca volvulus. Mol Biochem Parasitol 111: 243-251, 2000.
152. Lüersen K, Walter RD, and Müller S. The putative gammaglutamylcysteine synthetase from Plasmodium falciparum contains large insertions and a variable tandem repeat. Mol Biochem Parasitol 98: 131-142, 1999. (Pubitemid 29027935)
153. Lüersen K, Walter RD, and Müller S. Plasmodium falciparum- infected red blood cells depend on a functional glutathione de novo synthesis attributable to an enhanced loss of glutathione. Biochem J 346 Pt 2: 545-552, 2000. (Pubitemid 30148144)
154. Lujan HD and Nash TE. The uptake and metabolism of cysteine by Giardia lamblia trophozoites. J Eukaryot Microbiol 41: 169-175, 1994. (Pubitemid 2084153)
155. Luo JL, Huang CS, Babaoglu K, and Anderson ME. Novel kinetics of mammalian glutathione synthetase: characterization of gamma-glutamyl substrate cooperative binding. Biochem Biophys Res Commun 275: 577-581, 2000.
156. Maiorino M, Pierce R, and Flohé L. Product of the Schistosoma mansoni glutathione peroxidase gene is a selenium containing phospholipid hydroperoxide glutathione peroxidase (PHGPx) sharing molecular weight and substrate specificity with its mammalian counterpart. Biomed Environ Sci 10: 209-213, 1997. (Pubitemid 127472081)
157. Marquez VE, Arias DG, Piattoni CV, Robello C, Iglesias AA, and Guerrero SA. Cloning, expression, and characterization of a dithiol glutaredoxin from Trypanosoma cruzi. Antioxid Redox Signal 12: 787-792, 2010.
158. Marva E, Golenser J, Cohen A, Kitrossky N, Har-el R, and Chevion M. The effects of ascorbate-induced free radicals on Plasmodium falciparum. Trop Med Parasitol 43: 17-23, 1992.
159. Mei H, Thakur A, Schwartz J, and Lo Verde PT. Expression and characterization of glutathione peroxidase activity in the human blood fluke Schistosoma mansoni. Infect Immun 64: 4299-4306, 1996. (Pubitemid 26318156)
160. Meierjohann S, Walter RD, and Müller S. Glutathione synthetase from Plasmodium falciparum. Biochem J 363: 833- 838, 2002.
161. Milman N, Motyka SA, Englund PT, Robinson D, and Shlomai J. Mitochondrial origin-binding protein UMSBP mediates DNA replication and segregation in trypanosomes. Proc Natl Acad Sci U S A 104: 19250-19255, 2007.
162. Montemartini M, Nogoceke E, Singh M, Steinert P, Flohé L, and Kalisz HM. Sequence analysis of the tryparedoxin peroxidase gene from Crithidia fasciculata and its functional expression in Escherichia coli. J Biol Chem 273: 4864-4871, 1998. (Pubitemid 28108635)
163. Morrison HG, McArthur AG, Gillin FD, Aley SB, Adam RD, Olsen GJ, Best AA, Cande WZ, Chen F, Cipriano MJ, Davids BJ, Dawson SC, Elmendorf HG, Hehl AB, Holder ME, Huse SM, Kim UU, Lasek-Nesselquist E, Manning G, Nigam A, Nixon JE, Palm D, Passamaneck NE, Prabhu A, Reich CI, Reiner DS, Samuelson J, Svard SG, and Sogin ML. Genomic minimalism in the early diverging intestinal parasite Giardia lamblia. Science 317: 1921-1926, 2007. (Pubitemid 47509437)
164. Motyka SA, Drew ME, Yildirir G, and Englund PT. Overexpression of a cytochrome b5 reductase-like protein causes kinetoplast DNA loss in Trypanosoma brucei. J Biol Chem 281: 18499-18506, 2006. (Pubitemid 44035509)
165. Moutiez M, Aumercier M, Teissier E, Parmentier B, Tartar A, and Sergheraert C. Reduction of a trisulfide derivative of glutathione by glutathione reductase. Biochem Biophys Res Commun 202: 1380-1386, 1994. (Pubitemid 24265920)
166. Moutiez M, Meziene-Cherif D, Aumercier M, Sergheraert C, and Tartar A. Compared reactivities of trypanothione and glutathione in conjugation reactions. Chem Pharm Bull 42: 2641-2644, 1994.
167. Mueller EG. Trafficking in persulfides: delivering sulfur in biosynthetic pathways. Nat Chem Biol 2: 185-194, 2006.
168. Mukherjee A, Roy G, Guimond C, and Ouellette M. The gamma- glutamylcysteine synthetase gene of Leishmania is essential and involved in response to oxidants. Mol Microbiol 74: 914-927, 2009.
169. Müller S. Redox and antioxidant systems of the malaria parasite Plasmodium falciparum. Mol Microbiol 53: 1291-1305, 2004. (Pubitemid 39209105)
170. Müller S, Gilberger TW, Fairlamb AH, and Walter RD. Molecular characterization and expression of Onchocerca volvulus glutathione reductase. Biochem J 325 (Pt 3): 645-651, 1997. (Pubitemid 27367753)
171. Müller T, Johann L, Jannack B, Bruckner M, Lanfranchi DA, Bauer H, Sanchez C, Yardley V, Deregnaucourt C, Schrevel J, Lanzer M, Schirmer RH, and Davioud-Charvet E. Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones-a new strategy to combat malarial parasites. J Am Chem Soc 133: 11557-11571, 2011.
172. Murray HW and Nathan CF. Macrophage microbicidal mechanisms in vivo: reactive nitrogen versus oxygen intermediates in the killing of intracellular visceral Leishmania donovani. J Exp Med 189: 741-746, 1999. (Pubitemid 29193376)
173. Nickel C, Rahlfs S, Deponte M, Koncarevic S, and Becker K. Thioredoxin networks in the malarial parasite Plasmodium falciparum. Antioxid Redox Signal 8: 1227-1239, 2006. (Pubitemid 44182421)
174. Nogoceke E, Gommel DU, Kiess M, Kalisz HM, and Flohé L. A unique cascade of oxidoreductases catalyses trypanothione- mediated peroxide metabolism in Crithidia fasciculata. Biol Chem 378: 827-836, 1997. (Pubitemid 27388943)
175. Nozaki T, Ali V, and Tokoro M. Sulfur-containing amino acid metabolism in parasitic protozoa. Adv Parasitol 60: 1-99, 2005. (Pubitemid 41446921)
176. Nozaki T, Asai T, Sanchez LB, Kobayashi S, Nakazawa M, and Takeuchi T. Characterization of the gene encoding serine acetyltransferase, a regulated enzyme of cysteine biosynthesis from the protist parasites Entamoeba histolytica and Entamoeba dispar. Regulation and possible function of the cysteine biosynthetic pathway in Entamoeba. J Biol Chem 274: 32445-32452, 1999.
177. Nozaki T, Shigeta Y, Saito-Nakano Y, Imada M, and Kruger WD. Characterization of transsulfuration and cysteine biosynthetic pathways in the protozoan hemoflagellate, Trypanosoma cruzi. Isolation and molecular characterization of cystathionine beta-synthase and serine acetyltransferase from Trypanosoma. J Biol Chem 276: 6516-6523, 2001.
178. Olin-Sandoval V, Moreno-Sanchez R, and Saavedra E. Targeting trypanothione metabolism in trypanosomatid human parasites. Curr Drug Targets 11: 1614-1630, 2010.
179. Onn I, Milman-Shtepel N, and Shlomai J. Redox potential regulates binding of universal minicircle sequence binding protein at the kinetoplast DNA replication origin. Eukaryot Cell 3: 277-287, 2004. (Pubitemid 38497967)
180. Otero L, Bonilla M, Protasio AV, Fernandez C, Gladyshev VN, and Salinas G. Thioredoxin and glutathione systems differ in parasitic and free-living platyhelminths. BMC Genomics 11: 237, 2010.
181. Oza SL, Ariyanayagam MR, Aitcheson N, and Fairlamb AH. Properties of trypanothione synthetase from Trypanosoma brucei. Mol Biochem Parasitol 131: 25-33, 2003. (Pubitemid 37101176)
182. Oza SL, Ariyanayagam MR, and Fairlamb AH. Characterization of recombinant glutathionylspermidine synthetase/ amidase from Crithidia fasciculata. Biochem J 364: 679-686, 2002. (Pubitemid 34680843)
183. Oza SL, Chen S, Wyllie S, Coward JK, and Fairlamb AH. ATP-dependent ligases in trypanothione biosynthesis-kinetics of catalysis and inhibition by phosphinic acid pseudopeptides. FEBS J 275: 5408-5421, 2008.
184. Oza SL, Shaw MP, Wyllie S, and Fairlamb AH. Trypanothione biosynthesis in Leishmania major. Mol Biochem Parasitol 139: 107-116, 2005. (Pubitemid 40029602)
185. Oza SL, Tetaud E, Ariyanayagam MR, Warnon SS, and Fairlamb AH. A single enzyme catalyses formation of trypanothione from glutathione and spermidine in Trypanosoma cruzi. J Biol Chem 277: 35853-35861, 2002.
186. Padmanabhan PK, Mukherjee A, and Madhubala R. Characterization of the gene encoding glyoxalase II from Leishmania donovani: a potential target for anti-parasite drugs. Biochem J 393: 227-234, 2006. (Pubitemid 43049319)
187. Padmanabhan PK, Mukherjee A, Singh S, Chattopadhyaya S, Gowri VS, Myler PJ, Srinivasan N, and Madhubala R. Glyoxalase I from Leishmania donovani: a potential target for anti-parasite drug. Biochem Biophys Res Commun 337: 1237-1248, 2005. (Pubitemid 41505256)
188. Page-Sharp M, Behm CA, and Smith GD. Tritrichomonas foetus and Trichomonas vaginalis: the pattern of inactivation of hydrogenase activity by oxygen and activities of catalase and ascorbate peroxidase. Microbiology 142 (Pt 1): 207-211, 1996. (Pubitemid 26032063)
189. Pal S, Dolai S, Yadav RK, and Adak S. Ascorbate peroxidase from Leishmania major controls the virulence of infective stage of promastigotes by regulating oxidative stress. PLoS One 5: e11271, 2010.
190. Pastrana-Mena R, Dinglasan RR, Franke-Fayard B, Vega- Rodriguez J, Fuentes-Caraballo M, Baerga-Ortiz A, Coppens I, Jacobs-Lorena M, Janse CJ, and Serrano AE. Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito. J Biol Chem 285: 27045-27056, 2010.
191. Penketh PG, Kennedy WP, Patton CL, and Sartorelli AC. Trypanosomatid hydrogen peroxide metabolism. FEBS Lett 221: 427-431, 1987.
192. Penketh PG and Klein RA. Hydrogen peroxide metabolism in Trypanosoma brucei. Mol Biochem Parasitol 20: 111-121, 1986. (Pubitemid 16058243)
193. Perez-Pertejo Y, Reguera RM, Villa H, Garcia-Estrada C, Balana-Fouce R, Pajares MA, and Ordonez D. Leishmania donovani methionine adenosyltransferase. Role of cysteine residues in the recombinant enzyme. Eur J Biochem 270: 28-35, 2003. (Pubitemid 36056935)
194. Persson K, Aslund L, Grahn B, Hanke J, and Heby O. Trypanosoma cruzi has not lost its S-adenosylmethionine decarboxylase: characterization of the gene and the encoded enzyme. Biochem J 333 (Pt 3): 527-537, 1998. (Pubitemid 28398517)
195. Persson L. Ornithine decarboxylase and S-adenosylmethionine decarboxylase in trypanosomatids. Biochem Soc Trans 35: 314-317, 2007. (Pubitemid 46596498)
196. Phillips MA, Coffino P, and Wang CC. Cloning and sequencing of the ornithine decarboxylase gene from Trypanosoma brucei. Implications for enzyme turnover and selective difluoromethylornithine inhibition. J Biol Chem 262: 8721-8727, 1987. (Pubitemid 17102675)
197. Phillips MA, Coffino P, and Wang CC. Trypanosoma brucei ornithine decarboxylase: enzyme purification, characterization, and expression in Escherichia coli. J Biol Chem 263: 17933-17941, 1988. (Pubitemid 19005068)
198. Piacenza L, Peluffo G, Alvarez MN, Kelly JM, Wilkinson SR, and Radi R. Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage- and endogenously- derived peroxynitrite. Biochem J 410: 359-368, 2008. (Pubitemid 351346194)
199. Piacenza L, Zago MP, Peluffo G, Alvarez MN, Basombrio MA, and Radi R. Enzymes of the antioxidant network as novel determiners of Trypanosoma cruzi virulence. Int J Parasitol 39: 1455-1464, 2009.
200. Piattoni CV, Blancato VS, Miglietta H, Iglesias AA, and Guerrero SA. On the occurrence of thioredoxin in Trypanosoma cruzi. Acta Trop 97: 151-160, 2006. (Pubitemid 43087748)
201. Piñeyro MD, Parodi-Talice A, Portela M, Arias DG, Guerrero SA, and Robello C. Molecular characterization and interactome analysis of Trypanosoma cruzi Tryparedoxin 1. J Proteomics 74: 1683-1692, 2011.
202. Rada P, Smid O, Sutak R, Dolezal P, Pyrih J, Zarsky V, Montagne JJ, Hrdy I, Camadro JM, and Tachezy J. The monothiol single-domain glutaredoxin is conserved in the highly reduced mitochondria of Giardia intestinalis. Eukaryot Cell 8: 1584-1591, 2009.
203. Rahlfs S, Fischer M, and Becker K. Plasmodium falciparum possesses a classical glutaredoxin and a second, glutaredoxin- like protein with a PICOT homology domain. J Biol Chem 276: 37133-37140, 2001.
204. Rajan TV, Paciorkowski N, Kalajzic I, and McGuiness C. Ascorbic acid is a requirement for the morphogenesis of the human filarial parasite Brugia malayi. J Parasitol 89: 868-870, 2003. (Pubitemid 37151601)
205. Ray D and Williams DL. Characterization of the phytochelatin synthase of Schistosoma mansoni. PLoS Negl Trop Dis 5: e1168, 2011.
206. Reckenfelderbäumer N and Krauth-Siegel RL. Catalytic properties, thiol pK value, and redox potential of Trypanosoma brucei tryparedoxin. J Biol Chem 277: 17548-17555, 2002. (Pubitemid 34967556)
207. Reckenfelderbäumer N, Lüdemann H, Schmidt H, Steverding D, and Krauth-Siegel RL. Identification and functional characterization of thioredoxin from Trypanosoma brucei brucei. J Biol Chem 275: 7547-7552, 2000. (Pubitemid 30159652)
208. Reguera RM, Balana-Fouce R, Perez-Pertejo Y, Fernandez FJ, Garcia-Estrada C, Cubria JC, Ordonez C, and Ordonez D. Cloning expression and characterization of methionine adenosyltransferase in Leishmania infantum promastigotes. J Biol Chem 277: 3158-3167, 2002. (Pubitemid 34953177)
209. Reguera RM, Balana-Fouce R, Showalter M, Hickerson S, and Beverley SM. Leishmania major lacking arginase (ARG) are auxotrophic for polyamines but retain infectivity to susceptible BALB/c mice. Mol Biochem Parasitol 165: 48- 56, 2009.
210. Reguera RM, Redondo CM, Perez-Pertejo Y, and Balana- Fouce R. S-Adenosylmethionine in protozoan parasites: functions, synthesis and regulation. Mol Biochem Parasitol 152: 1-10, 2007.
211. Roberts SC, Jiang Y, Jardim A, Carter NS, Heby O, and Ullman B. Genetic analysis of spermidine synthase from Leishmania donovani. Mol Biochem Parasitol 115: 217- 226, 2001.
212. Roberts SC, Scott J, Gasteier JE, Jiang Y, Brooks B, Jardim A, Carter NS, Heby O, and Ullman B. S-adenosylmethionine decarboxylase from Leishmania donovani. Molecular, genetic, and biochemical characterization of null mutants and overproducers. J Biol Chem 277: 5902-5909, 2002. (Pubitemid 34968370)
213. Roberts SC, Tancer MJ, Polinsky MR, Gibson KM, Heby O, and Ullman B. Arginase plays a pivotal role in polyamine precursor metabolism in Leishmania. Characterization of gene deletion mutants. J Biol Chem 279: 23668-23678, 2004. (Pubitemid 38685683)
214. Romao S, Castro H, Sousa C, Carvalho S, and Tomas AM. The cytosolic tryparedoxin of Leishmania infantum is essential for parasite survival. Int J Parasitol 39: 703-711, 2009.
215. Sarma GN, Savvides SN, Becker K, Schirmer M, Schirmer RH, and Karplus PA. Glutathione reductase of the malarial parasite Plasmodium falciparum: crystal structure and inhibitor development. J Mol Biol 328: 893-907, 2003. (Pubitemid 36506894)
216. Schlecker T, Schmidt A, Dirdjaja N, Voncken F, Clayton C, and Krauth-Siegel RL. Substrate specificity, localization, and essential role of the glutathione peroxidase-type tryparedoxin peroxidases in Trypanosoma brucei. J Biol Chem 280: 14385-14394, 2005. (Pubitemid 40562777)
217. Schmidt A, Clayton CE, and Krauth-Siegel RL. Silencing of the thioredoxin gene in Trypanosoma brucei brucei. Mol Biochem Parasitol 125: 207-210, 2002. (Pubitemid 35449261)
218. Schmidt H and Krauth-Siegel RL. Functional and physicochemical characterization of the thioredoxin system in Trypanosoma brucei. J Biol Chem 278: 46329-46336, 2003. (Pubitemid 37452203)
219. Seiler A, Schneider M, Forster H, Roth S, Wirth EK, Culmsee C, Plesnila N, Kremmer E, Radmark O, Wurst W, Bornkamm GW, Schweizer U, and Conrad M. Glutathione peroxidase 4 senses and translates oxidative stress into 12/ 15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8: 237-248, 2008.
220. Sela D, Yaffe N, and Shlomai J. Enzymatic mechanism controls redox-mediated protein-DNA interactions at the replication origin of kinetoplast DNA minicircles. J Biol Chem 283: 32034-32044, 2008.
221. Selkirk ME, Smith VP, Thomas GR, and Gounaris K. Resistance of filarial nematode parasites to oxidative stress. Int J Parasitol 28: 1315-1332, 1998. (Pubitemid 28386943)
222. Selzer PM, Hesse F, Hamm-Kunzelmann B, Muhlstadt K, Echner H, and Duszenko M. Down regulation of S-adenosyl- L-methionine decarboxylase activity of Trypanosoma brucei during transition from long slender to short stumpylike forms in axenic culture. Eur J Cell Biol 69: 173-179, 1996. (Pubitemid 26052528)
223. Shahi SK, Krauth-Siegel RL, and Clayton CE. Overexpression of the putative thiol conjugate transporter TbMRPA causes melarsoprol resistance in Trypanosoma brucei. Mol Microbiol 43: 1129-1138, 2002. (Pubitemid 34304532)
224. Shames SL, Fairlamb AH, Cerami A, and Walsh CT. Purification and characterization of trypanothione reductase from Crithidia fasciculata, a newly discovered member of the family of disulfide-containing flavoprotein reductases. Biochemistry 25: 3519-3526, 1986.
225. Sherman IW. Transport of amino acids and nucleic acid precursors in malarial parasites. Bull World Health Organ 55: 211-225, 1977. (Pubitemid 8234190)
226. Sherman IW. Biochemistry of Plasmodium (malarial parasites). Microbiol Rev 43: 453-495, 1979. (Pubitemid 10125952)
227. Shim H and Fairlamb AH. Levels of polyamines, glutathione and glutathione-spermidine conjugates during growth of the insect trypanosomatid Crithidia fasciculata. J Gen Microbiol 134: 807-817, 1988. (Pubitemid 18085133)
228. Steenkamp DJ. Trypanosomal antioxidants and emerging aspects of redox regulation in the trypanosomatids. Antioxid Redox Signal 4: 105-121, 2002. (Pubitemid 34260691)
229. Steenkamp DJ and Spies HS. Identification of a major low-molecular-mass thiol of the trypanosomatid Crithidia fasciculata as ovothiol A. Facile isolation and structural analysis of the bimane derivative. Eur J Biochem 223: 43-50, 1994. (Pubitemid 24221644)
230. Steenkamp DJ, Weldrick D, and Spies HS. Studies on the biosynthesis of ovothiol A. Identification of 4-mercaptohistidine as an intermediate. Eur J Biochem 242: 557-566, 1996.
231. Steinert P, Plank-Schumacher K, Montemartini M, Hecht HJ, and Flohé L. Permutation of the active site motif of tryparedoxin 2. Biol Chem 381: 211-219, 2000. (Pubitemid 30179555)
232. Stocker R, Hunt NH, Buffinton GD, Weidemann MJ, Lewis- Hughes PH, and Clark IA. Oxidative stress and protective mechanisms in erythrocytes in relation to Plasmodium vinckei load. Proc Natl Acad Sci U S A 82: 548-551, 1985. (Pubitemid 15128305)
233. Stocker R, Hunt NH, Weidemann MJ, and Clark IA. Protection of vitamin E from oxidation by increased ascorbic acid content within Plasmodium vinckei-infected erythrocytes. Biochim Biophys Acta 876: 294-299, 1986. (Pubitemid 16014864)
234. Stocker R, Weidemann MJ, and Hunt NH. Possible mechanisms responsible for the increased ascorbic acid content of Plasmodium vinckei-infected mouse erythrocytes. Biochim Biophys Acta 881: 391-397, 1986. (Pubitemid 16033455)
235. Sturm N, Jortzik E, Mailu BM, Koncarevic S, Deponte M, Forchhammer K, Rahlfs S, and Becker K. Identification of proteins targeted by the thioredoxin superfamily in Plasmodium falciparum. PLoS Pathog 5: e1000383, 2009.
236. Sullivan FX, Shames SL, and Walsh CT. Expression of Trypanosoma congolense trypanothione reductase in Escherichia coli: overproduction, purification, and characterization. Biochemistry 28: 4986-4992, 1989. (Pubitemid 19162743)
237. Sun QA, Kirnarsky L, Sherman S, and Gladyshev VN. Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems. Proc Natl Acad Sci U S A 98: 3673-3678, 2001. (Pubitemid 32249829)
238. Sztajer H, Gamain B, Aumann KD, Slomianny C, Becker K, Brigelius-Flohe R, and Flohé L. The putative glutathione peroxidase gene of Plasmodium falciparum codes for a thioredoxin peroxidase. J Biol Chem 276: 7397-7403, 2001.
239. Tabor H and Tabor CW. Isolation, characterization, and turnover of glutathionylspermidine from Escherichia coli. J Biol Chem 250: 2648-2654, 1975.
240. Taladriz S, Ramiro MJ, Hanke T, and Larraga V. Sadenosylmethionine decarboxylase from Leishmania infantum promastigotes: molecular cloning and differential expression. Parasitol Res 88: 421-426, 2002. (Pubitemid 34328088)
241. Tang L, Gounaris K, Griffiths C, and Selkirk ME. Heterologous expression and enzymatic properties of a selenium-independent glutathione peroxidase from the parasitic nematode Brugia pahangi. J Biol Chem 270: 18313- 18318, 1995.
242. Taylor MC, Kaur H, Blessington B, Kelly JM, and Wilkinson SR. Validation of spermidine synthase as a drug target in African trypanosomes. Biochem J 409: 563- 569, 2008.
243. Tekwani BL, Bacchi CJ, and Pegg AE. Putrescine activated S-adenosylmethionine decarboxylase from Trypanosoma brucei brucei. Mol Cell Biochem 117: 53-61, 1992.
244. Tekwani BL and Mehlotra RK. Molecular basis of defence against oxidative stress in Entamoeba histolytica and Giardia lamblia. Microbes Infect 1: 385-394, 1999.
245. Tetaud E, Giroud C, Prescott AR, Parkin DW, Baltz D, Biteau N, Baltz T, and Fairlamb AH. Molecular characterisation of mitochondrial and cytosolic trypanothionedependent tryparedoxin peroxidases in Trypanosoma brucei. Mol Biochem Parasitol 116: 171-183, 2001. (Pubitemid 32777826)
246. Tetaud E, Manai F, Barrett MP, Nadeau K, Walsh CT, and Fairlamb AH. Cloning and characterization of the two enzymes responsible for trypanothione biosynthesis in Crithidia fasciculata. J Biol Chem 273: 19383-19390, 1998. (Pubitemid 28366984)
247. Torrie LS, Wyllie S, Spinks D, Oza SL, Thompson S, Harrison JR, Gilbert IH, Wyatt PG, Fairlamb AH, and Frearson JA. Chemical validation of trypanothione synthetase: a potential drug target for human trypanosomiasis. J Biol Chem 284: 36137-36145, 2009.
248. Tovar J, CunninghamML, Smith AC, Croft SL, and Fairlamb AH. Down-regulation of Leishmania donovani trypanothione reductase by heterologous expression of a trans-dominant mutant homologue: effect on parasite intracellular survival. Proc Natl Acad Sci U S A 95: 5311-5316, 1998. (Pubitemid 28208594)
249. Trujillo M, Budde H, Piñeyro MD, Stehr M, Robello C, Flohé L, and Radi R. Trypanosoma brucei and Trypanosoma cruzi tryparedoxin peroxidases catalytically detoxify peroxynitrite via oxidation of fast reacting thiols. J Biol Chem 279: 34175-34182, 2004. (Pubitemid 39318040)
250. Trujillo M, Ferrer-Sueta G, Thomson L, Flohé L, and Radi R. Kinetics of peroxiredoxins and their role in the decomposition of peroxynitrite. Subcell Biochem 44: 83-113, 2007.
251. Turner E, Hager LJ, and Shapiro BM. Ovothiol replaces glutathione peroxidase as a hydrogen peroxide scavenger in sea urchin eggs. Science 242: 939-941, 1988.
252. Turner E, Klevit R, Hager LJ, and Shapiro BM. Ovothiols, a family of redox-active mercaptohistidine compounds from marine invertebrate eggs. Biochemistry 26: 4028-4036, 1987.
253. Urscher M, Alisch R, and Deponte M. The glyoxalase system of malaria parasites - implications for cell biology and general glyoxalase research. Semin Cell Dev Biol 22: 262-270, 2011.
254. Van Dobbenburgh OA, Houwen B, Jurjens H, Marrink J, Halie MR, and Nieweg HO. Plasma spermidine concentrations as early indication of response to therapy in human myeloma. J Clin Pathol 36: 804-807, 1983. (Pubitemid 13069315)
255. van Zandbergen G, Bollinger A, Wenzel A, Kamhawi S, Voll R, Klinger M, Müller A, Hölscher C, Herrmann M, Sacks D, Solbach W, and Laskay T. Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum. Proc Natl Acad Sci U S A 103: 13837-13842, 2006. (Pubitemid 44413994)
256. Vega-Rodriguez J, Franke-Fayard B, Dinglasan RR, Janse CJ, Pastrana-Mena R, Waters AP, Coppens I, Rodriguez- Orengo JF, Srinivasan P, Jacobs-Lorena M, and Serrano AE. The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission. PLoS Pathog 5: e1000302, 2009.
257. Vicente JB, Ehrenkaufer GM, Saraiva LM, Teixeira M, and Singh U. Entamoeba histolytica modulates a complex repertoire of novel genes in response to oxidative and nitrosative stresses: implications for amebic pathogenesis. Cell Microbiol 11: 51-69, 2009.
258. Vickers TJ, Greig N, and Fairlamb AH. A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in Leishmania major. Proc Natl Acad Sci U S A 101: 13186-13191, 2004. (Pubitemid 39209640)
259. Vickers TJ, Wyllie S, and Fairlamb AH. Leishmania major elongation factor 1B complex has trypanothione S-transferase and peroxidase activity. J Biol Chem 279: 49003-49009, 2004. (Pubitemid 39642165)
260. Vogt RN, Spies HS, and Steenkamp DJ. The biosynthesis of ovothiol A (N-methyl-4-mercaptohistidine). Identification of S-(4¢-L-histidyl)-L- cysteine sulfoxide as an intermediate and the products of the sulfoxide lyase reaction. Eur J Biochem 268: 5229-5241, 2001. (Pubitemid 32948348)
261. Vogt RN and Steenkamp DJ. The metabolism of Snitrosothiols in the trypanosomatids: the role of ovothiol A and trypanothione. Biochem J 371: 49-59, 2003. (Pubitemid 36458078)
262. Wanderley JL, Pinto da Silva LH, Deolindo P, Soong L, Borges VM, Prates DB, de Souza AP, Barral A, Balanco JM, do Nascimento MT, Saraiva EM, and Barcinski MA. Cooperation between apoptotic and viable metacyclics enhances the pathogenesis of Leishmaniasis. PLoS One 4: e5733, 2009.
263. Wang XF and Cynader MS. Pyruvate released by astrocytes protects neurons from copper-catalyzed cysteine neurotoxicity. J Neurosci 21: 3322-3331, 2001. (Pubitemid 32422797)
264. Weaver KH and Rabenstein DL. Thiol/disulfide exchange reactions of ovothiol A with glutathione. J Org Chem 60: 1904-1907, 1995.
265. Wendler A, Irsch T, Rabbani N, Thornalley PJ, and Krauth- Siegel RL. Glyoxalase II does not support methylglyoxal detoxification but serves as a general trypanothione thioesterase in African trypanosomes. Mol Biochem Parasitol 163: 19-27, 2009.
266. Westrop GD, Georg I, and Coombs GH. The mercaptopyruvate sulfurtransferase of Trichomonas vaginalis links cysteine catabolism to the production of thioredoxin persulfide. J Biol Chem 284: 33485-33494, 2009.
267. Westrop GD, Goodall G, Mottram JC, and Coombs GH. Cysteine biosynthesis in Trichomonas vaginalis involves cysteine synthase utilizing O-phosphoserine. J Biol Chem 281: 25062-25075, 2006. (Pubitemid 44401894)
268. Wilkinson SR, Horn D, Prathalingam SR, and Kelly JM. RNA interference identifies two hydroperoxide metabolizing enzymes that are essential to the bloodstream form of the African trypanosome. J Biol Chem 278: 31640-31646, 2003. (Pubitemid 37048342)
269. Wilkinson SR, Meyer DJ, and Kelly JM. Biochemical characterization of a trypanosome enzyme with glutathione- dependent peroxidase activity. Biochem J 352: 755-761, 2000. (Pubitemid 32015032)
270. Wilkinson SR, Meyer DJ, Taylor MC, Bromley EV, Miles MA, and Kelly JM. The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin. J Biol Chem 277: 17062-17071, 2002. (Pubitemid 34967736)
271. Wilkinson SR, Obado SO, Mauricio IL, and Kelly JM. Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum. Proc Natl Acad Sci U S A 99: 13453-13458, 2002. (Pubitemid 35215402)
272. Wilkinson SR, Prathalingam SR, Taylor MC, Horn D, and Kelly JM. Vitamin C biosynthesis in trypanosomes: a role for the glycosome. Proc Natl Acad Sci U S A 102: 11645- 11650, 2005.
273. Wilkinson SR, Taylor MC, Touitha S, Mauricio IL, Meyer DJ, and Kelly JM. TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum. Biochem J 364: 787- 794, 2002.
274. Wilkinson SR, Temperton NJ, Mondragon A, and Kelly JM. Distinct mitochondrial and cytosolic enzymes mediate trypanothione-dependent peroxide metabolism in Trypanosoma cruzi. J Biol Chem 275: 8220-8225, 2000. (Pubitemid 30159739)
275. Willert EK, Fitzpatrick R, and Phillips MA. Allosteric regulation of an essential trypanosome polyamine biosynthetic enzyme by a catalytically dead homolog. Proc Natl Acad Sci U S A 104: 8275-8280, 2007. (Pubitemid 47175478)
276. Williams RA, Kelly SM, Mottram JC, and Coombs GH. 3- Mercaptopyruvate sulfurtransferase of Leishmania contains an unusual C-terminal extension and is involved in thioredoxin and antioxidant metabolism. J Biol Chem 278: 1480- 1486, 2003.
277. Williams RA, Westrop GD, and Coombs GH. Two pathways for cysteine biosynthesis in Leishmania major. Biochem J 420: 451-462, 2009.
278. Wyatt PG, Gilbert IH, Read KD, and Fairlamb AH. Target validation: linking target and chemical properties to desired product profile. Curr Top Med Chem 11: 1275-1283, 2011.
279. Wyllie S, Mandal G, Singh N, Sundar S, Fairlamb AH, and Chatterjee M. Elevated levels of tryparedoxin peroxidase in antimony unresponsive Leishmania donovani field isolates. Mol Biochem Parasitol 173: 162-164, 2010.
280. Wyllie S, Oza SL, Patterson S, Spinks D, Thompson S, and Fairlamb AH. Dissecting the essentiality of the bifunctional trypanothione synthetase-amidase in Trypanosoma brucei using chemical and genetic methods. Mol Microbiol 74: 529- 540, 2009.
281. Wyllie S, Vickers TJ, and Fairlamb AH. Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials. Antimicrob Agents Chemother 52: 1359-1365, 2008. (Pubitemid 351521999)
282. Xiao Y, McCloskey DE, and Phillips MA. RNA interference-mediated silencing of ornithine decarboxylase and spermidine synthase genes in Trypanosoma brucei provides insight into regulation of polyamine biosynthesis. Eukaryot Cell 8: 747-755, 2009.
283. Xue M, Rabbani N, and Thornalley PJ. Glyoxalase in ageing. Semin Cell Dev Biol 22: 293-301, 2011.
284. Yarlett N, Garofalo J, Goldberg B, Ciminelli MA, Ruggiero V, Sufrin JR, and Bacchi CJ. S-adenosylmethionine synthetase in bloodstream Trypanosoma brucei. Biochim Biophys Acta 1181: 68-76, 1993. (Pubitemid 23087524)
285. Yoo MH, Gu X, Xu XM, Kim JY, Carlson BA, Patterson AD, Cai H, Gladyshev VN, and Hatfield DL. Delineating the role of glutathione peroxidase 4 in protecting cells against lipid hydroperoxide damage and in Alzheimer's disease. Antioxid Redox Signal 12: 819-827, 2010.
286. Zhang Y, Konig I, and Schirmer RH. Glutathione reductase- deficient erythrocytes as host cells of malarial parasites. Biochem Pharmacol 37: 861-865, 1988. (Pubitemid 18058457)
287. Zhang YA, Hempelmann E, and Schirmer RH. Glutathione reductase inhibitors as potential antimalarial drugs. Effects of nitrosoureas on Plasmodium falciparum in vitro. Biochem Pharmacol 37: 855-860, 1988. (Pubitemid 18058456)