Trypanothione is a unusual form of glutathione that 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 contains two molecules of glutathione joined by a polyamine linker. Trypanothione is not present in humans and is essential for the survival of the parasites. The enzymes that make and use this molecule are therefore seen as targets for the development of new drugs to treat these diseases (2). Glutathione (GSH), whose IUPAC name is 2-amino-5-{[2-[(carboxymethyl)amino]-1-(mercaptomethyl)-2-oxoethyl]amino}-5-oxopentanoic acid, is γ-glutamylcysteinylglycine, a tripeptide. ... Species see text Leishmania is a genus of trypanosome protozoa, and is the parasite responsible for the disease leishmaniasis. ... Genera Blastocrithidia Crithidia Endotrypanum Herpetomonas Leishmania Leptomonas Phytomonas Trypanosoma Wallaceina Trypanosomes are a group of kinetoplastid protozoa distinguished by having only a single flagellum. ... Sleeping sickness or African trypanosomiasis is a parasitic disease in people and in animals. ... The polyamines are organic compounds, that have two or more primary amino groups, such as putrescine, spermidine, and spermine, that are growth factors in both eucaryotic and procaryotic cells. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ...

Trypanothione-dependent enzymes include reductases, peroxidases, glyoxalases and transferases. Trypanothione reductase (TryR) was the first trypanothione-dependent enzyme to be discovered (EC 1.8.1.12). It is a NADPH-dependent flavoenzyme that reduces trypanothione disulphide. TryR is essential for the survival of these parasites both in vitro and in the human host.

A major function of trypanothione is in the defence against oxidative stress (3). 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 particulaly 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. Oxidative stress is a medical term for damage to animal or plant cells (and thereby the organs and tissues composed of those cells) caused by reactive oxygen species, which include (but are not limited to) superoxide, singlet oxygen, peroxynitrite or hydrogen peroxide. ... Peroxide has three distinct meanings: Colloquial meaning In common usage, peroxide is an aqueous solution of hydrogen peroxide (HOOH or H2O2) sold for use as a disinfectant or mild bleach. ... Hydrogen peroxide (H2O2) is a clear liquid, slightly more viscous than water. ... Catalase Catalase (human erythrocyte catalase: PDB 1DGF, EC 1. ... Thioredoxin Reductase (TR, TrxR) are the only known enzymes to reduce thioredoxin (Trx). ...

Image File history File links TryP_cycle. ...

External link

• Fairlamb lab

References