December 2007 - The Indian Society for Parasitology

98 Banyal and Sharmatransmembrane ectoenzyme. The majority of the exposure to ROS (Rahlfs et al., 2003).protein is extracellular with only the N-terminalmethionine and three lysine residues located inside theCONCLUSIONplasma membrane (Ruedig and Dringen, 2004). The There is a good evidence that glutathione playsenzyme hydrolyses glutamyl groups from glutathione important role in destroying ROS, free-radicals and(GSH) or glutathione-S-conjugates. In doing so, it can detoxification of xenobiotics that are formed duringtransfer γ-glutamyl groups to an amino acid, metabolism. As a result parasitic protozoa are a welldipeptide,water or another molecule of GSH. Through protected target for oxidant drugs. Only inhibitorsthe operation of the gammaglutamylcyclotransferase targeted to specific component of glutathionecycle, this enzyme has been implicated in the transport metabolism are able to destroy the parasite. Thisof amino acids into cells. Although GGT is most indirect parasite killing is particularly effective inactively operative in cells of the proximal tubules of drug resistant parasitic protozoa. Enzymes like γ-kidney but absent in human and rabbit erythrocytes GCS, GS, GR and GST of this metabolism have been(Srivastava et al., 2005). In Ascaris suum the enzyme studied among various protozoa. But still noshowed a molecular mass of 70 kDa, and was found to information is available about the other enzymes ofbe composed of two non-identical subunits of glutathione metabolism such as 5-oxoprolinase,molecular mass 43 and 30 kDa (Hussein and Walter,dipeptidase, γ-glutamyl transpeptidase and γ-1999).glutamylcyclotransferase. The identification andfunctional analysis of these protozoan enzymes8. γ-glutamyl cyclotransferase [(5-L-glutamyl)-Linvolvedin glutathione metabolism may be ofamino-acid 5-glutamyltrasferase (cyclizing) ECimportance in the context of improved chemotherapy.2.3.2.4)]: γ-glutamyl cyclotransferase catalyses thesynthesis of pyroglutamate from a gamma-glutamyl REFERENCESamino acid, also releasing the free amino acid. The Anderson ME. 1985. Determination of glutathione andenzyme acts on derivatives of glutamate, 2- glutathione disulphide in biological samples. Methodsaminobutyrate, alanine and glycine. The enzyme has Enzymol 113:548-555.been proposed to have a role in a gamma-glutamylAriyanayagam MR and Fairlamb AH. 1999. Entamoebacycle for amino acid transport into cells (Srivastava et histolytica lacks trypanothione metabolism. Mol Biochemal., 2005). Parasitol 103:61-69.OTHER SYSTEMS AND GLUTATHIONE Arrick BA, Griffith OW and Cerami A. 1981. Inhibition ofMETABOLISMglutathione synthesis as a chemotherapeutic strategy fortrypanosomiasis. J Exp Med 153:720-725.Thioredoxin system: Trichomonas and apicomplexanAtamna H and Ginsburg H. 1997. The malaria parasite suppliesprotozoan parasites have thioredoxin system glutathione to its host cell-investigation of glutathioneconsisting of a small low molecular weight transport and metabolism in human erythrocytes infectedthioredoxin (Trx) with a redox active disulphide (- with Plasmodium falciparum. Eur J Biochem 250:670-679.Cys-Gly-Pro-Cys-) that is reduced to a dithiol byAyi K, Cappadoro M, Branca M, Turini F and Arese P. 1998.NADPH and flavoprotein thioredoxin reductase Plasmodium falciparum glutathione metabolism and(TrxR) (Kanzok et al., 2000; Coombs et al., 2004). growth are independent of glutathione system of hostTrxR/Trx catalyzed the reduction of GSSG to GSH. A erythrocyte. FEBS Lett 424:257-261.high rate of reduction was observed in glutathioneBanyal HS and Fitch CD. 1982. Ferriprotoporphyrin IXreductase-deficient cells, which is helpful for certain binding substances and the mode of action of chloroquinestages of parasite (Kanzok et al., 2000). against malaria. Life Sc 31:1141-1144.Becker K, Tilley L, Vennerstrom JL, Roberts D, Rogerson S andGinsburg H. 2004. Oxidative stress in malaria parasite-Glutaredoxin system: Plasmodium possessesglutaredoxin system composed of small proteinglutaredoxin which also has a redox active disulphide(Cys-Pro-Tyr-Cys) that is reduced to dithiol by GSH,NADPH and GSSG reductase. Such reduction doesnot occur with thioredoxin reductase. The protein isinvolved in the reduction of protein-GS mixeddisulphides that are inevitably formed duringBanyal HS and Inselberg J. 1986. Plasmodium falciparum:induction, selection and characterization of pyrimethamineresistant mutants. Exp Parasitol 62:61-70.Becker K, Rahlfs S, Nickel C and Schirmer RH. 2003.Glutathione – functions and metabolism in the malarialparasite Plasmodium falciparum. Biol Chem 384:551-566.