Trypanothione (Mr = 721. 86 g/mol) is an unusual form of glutathione containing two molecules of glutathione joined by a spermidine (polyamine) linker. Glutathione ( GSH) is a Tripeptide. It contains an unusual Peptide linkage between the amine group of Cysteine and the Carboxyl Spermidine is a Polyamine involved in Cellular metabolism that can be used to stimulate the enzyme T7 RNA polymerase, a type of RNA polymerase The polyamines are organic compounds having two or more primary Amino groups - such as Putrescine, Cadaverine, Spermidine, and Spermine It is found in parasitic protozoa such as leishmania and trypanosomes. Leishmania is a Genus of Trypanosome Protozoa, and is the Parasite responsible for the disease Leishmaniasis. Trypanosomes are a group of Kinetoplastid protozoa distinguished by having only a single Flagellum. [1] These protozoal parasites are the cause of leishmaniasis, sleeping sickness and Chagas' disease. Leishmaniasis is a Disease caused by Protozoan Parasites that belong to the genus Leishmania and is transmitted by the bite of certain Sleeping sickness or human African trypanosomiasis is a Parasitic Disease of people and animals caused by Protozoa of species Chagas disease (doença de Chagas enfermedad de Chagas mal de Chagas in both languages also called American trypanosomiasis) is a tropical Parasitic Trypanothione was discovered by Alan Fairlamb. Alan Hutchison Fairlamb CBE, FRSE, FLS (born 30 April 1947, Newcastle upon Tyne, England) is a Wellcome It is unique to the Kinetoplastida and not found in other parasitic protozoa such as Entamoeba histolytica. The kinetoplastids are a group of Flagellate Protozoa, including a number of Parasites responsible for serious diseases in humans and other animals as well For the infection and disease caused by this parasite refer to Amoebiasis. [2] Since this thiol is absent from humans and is essential for the survival of the parasites, the enzymes that make and use this molecule are targets for the development of new drugs to treat these diseases. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins [3]
Trypanothione-dependent enzymes include reductases, peroxidases, glyoxalases and transferases. A reductase is an Enzyme which lowers the Activation energy for a reduction reaction. Peroxidases ( EC number 1111x are a large family of Enzymes A majority of peroxidase protein sequences can be found in the PeroxiBase database The glyoxalase system is a set of enzymes that carry out the Detoxification of Methylglyoxal and the other reactive Aldehydes that are produced as a normal In Biochemistry, a transferase is an Enzyme that catalyzes the transfer of a Functional group (e Trypanothione reductase (TryR) was the first trypanothione-dependent enzyme to be discovered (EC 1.8.1.12). It is an NADPH-dependent flavoenzyme that reduces trypanothione disulfide. TryR is essential for survival of these parasites both in vitro and in the human host. [4][5]
A major function of trypanothione is in the defence against oxidative stress. Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily [6] Here, trypanothione-dependent enzymes such as tryparedoxin peroxidase (TryP) reduce peroxides using electrons donated either directly from trypanothione, or via the redox intermediate tryparedoxin (TryX). A peroxide is a compound containing an Oxygen -oxygen single bond. Trypanothione-dependent hydrogen peroxide metabolism is particularly important in these organisms because they lack catalase. Hydrogen peroxide (H2O2 is a very pale blue liquid which appears colorless in a dilute solution slightly more Viscous than water Catalase is a common Enzyme found in nearly all living organisms where it functions to catalyze the decomposition of Hydrogen peroxide to Since the trypanosomatids also lack an equivalent of thioredoxin reductase, trypanothione reductase is the sole path that electrons can take from NADPH to these antioxidant enzymes. Thioredoxin Reductase (TR TrxR ( are the only known enzymes to reduce Thioredoxin (Trx
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References
- ^ Metabolism and functions of trypanothione in the Kinetoplastida. Fairlamb AH, Cerami A. Annu Rev Microbiol. 1992;46:695-729.
- ^ Entamoeba histolytica lacks trypanothione metabolism. Ariyanayagam MR, Fairlamb AH. Mol Biochem Parasitol. 1999 Sep 20;103(1):61-9.
- ^ Enzymes of the trypanothione metabolism as targets for antitrypanosomal drug development. Schmidt A, Krauth-Siegel RL. Curr Top Med Chem. 2002 Nov;2(11):1239-59.
- ^ Evidence that trypanothione reductase is an essential enzyme in Leishmania by targeted replacement of the tryA gene locus. Tovar J, Wilkinson S, Mottram JC, Fairlamb AH. Mol Microbiol. 1998 Jul;29(2):653-60.
- ^ Trypanosomes lacking trypanothione reductase are avirulent and show increased sensitivity to oxidative stress. Krieger S, Schwarz W, Ariyanayagam MR, Fairlamb AH, Krauth-Siegel RL, Clayton C. Mol Microbiol. 2000 Feb;35(3):542-52.
- ^ The parasite-specific trypanothione metabolism of trypanosoma and leishmania. Krauth-Siegel RL, Meiering SK, Schmidt H. Biol Chem. 2003 Apr;384(4):539-49.
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