Trypanothione is an unusual form of

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...

containing two molecules of glutathione joined by a

spermidine Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen. Function Spermidine is an aliphatic polyamine. Spermidine synthase (SP ...

( polyamine) linker. It is found in parasitic protozoa such as leishmania and trypanosomes. These protozoal parasites are the cause of leishmaniasis,

sleeping sickness African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species ''Trypanosoma brucei''. Humans are infected by two typ ...

and Chagas' disease. Trypanothione was discovered by Alan Fairlamb. Its structure was proven by chemical synthesis. It is unique to the

Kinetoplastida Kinetoplastida (or Kinetoplastea, as a class) is a group of flagellated protists belonging to the phylum Euglenozoa, and characterised by the presence of an organelle with a large massed DNA called kinetoplast (hence the name). The organisms are ...

and not found in other parasitic protozoa such as ''

Entamoeba histolytica ''Entamoeba histolytica'' is an anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 million people worldwid ...

''. 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. Trypanothione-dependent enzymes include reductases,

peroxidase Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides. Functionality Peroxidases typically ca ...

s, glyoxalases and

transferase A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups (e.g. a methyl or glycosyl group) from one molecule (called the donor) to another (called the acceptor). They are involved in hundreds of ...

s. Trypanothione-disulfide 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. A major function of trypanothione is in the defence against

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

. Here, trypanothione-dependent enzymes such as tryparedoxin peroxidase
TryP
reduce

peroxides In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable. The most common peroxide is hydrogen p ...

using electrons donated either directly from trypanothione, or via the redox intermediate tryparedoxin
TryX
. Trypanothione-dependent

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%� ...

metabolism is particularly important in these organisms because they lack catalase. Since the trypanosomatids also lack an equivalent of

thioredoxin reductase Thioredoxin reductases (TR, TrxR) () are enzymes that reduce thioredoxin (Trx). Two classes of thioredoxin reductase have been identified: one class in bacteria and some eukaryotes and one in animals. In bacteria TrxR also catalyzes the reduction ...

, trypanothione reductase is the sole path that electrons can take from NADPH to these antioxidant enzymes.

References

{{reflist Thiols Peptides