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Trypanothione. The glutathione moieties are shown in black and the polyamine linker in red.

Trypanothione (Mr = 721.86 g/mol) is a unusual form of glutathione containing two molecules of glutathione joined by a spermidine (polyamine) linker. It is found in parasitic protozoa such as leishmania and trypanosomes.[1] These protozoal parasites are the cause of leishmaniasis, sleeping sickness and Chagas' disease. Trypanothione was discovered by Alan Fairlamb. It is unique to the Kinetoplastida and not found in other parasitic protozoa such as Entamoeba histolytica.[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.[3]

Trypanothione-dependent enzymes include reductases, peroxidases, glyoxalases and transferases. Trypanothione reductase (TryR) was the first trypanothione-dependent enzyme to be discovered (EC It is a NADPH-dependent flavoenzyme that reduces trypanothione disulphide. 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.[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). Trypanothione-dependent hydrogen peroxide metabolism is particularly important in these organisms because they lack catalase. 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.

File:TryP cycle.jpg

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