Trypanothione is an unusual form of

glutathione Glutathione (GSH, ) is an organic compound with the chemical formula . It 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 ...

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. Function Spermidine is an Aliphatic compound, aliphatic polyamine. Spermidine synthase (SPDS) catalyzes its form ...

(

polyamine A polyamine is an organic compound having two or more amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. ...

) linker. It is found in parasitic protozoa such as

leishmania ''Leishmania'' () is a genus of parasitic protozoans, single-celled eukaryotic organisms of the trypanosomatid group that are responsible for the disease leishmaniasis. The parasites are transmitted by sandflies of the genus '' Phlebotomus'' ...

and trypanosomes. These protozoal parasites are the cause of

leishmaniasis Leishmaniasis is a wide array of clinical manifestations caused by protozoal parasites of the Trypanosomatida genus ''Leishmania''. It is generally spread through the bite of Phlebotominae, phlebotomine Sandfly, sandflies, ''Phlebotomus'' an ...

sleeping sickness African trypanosomiasis is an insect-borne parasitic infection of humans and other animals. Human African trypanosomiasis (HAT), also known as African sleeping sickness or simply sleeping sickness, is caused by the species '' Trypanosoma b ...

and

Chagas' disease Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by ''Trypanosoma cruzi''. It is spread mostly by insects in the subfamily Triatominae, known as "kissing bugs". The symptoms change throughout the in ...

. Trypanothione was discovered by Alan Fairlamb. Its structure was proven by chemical synthesis. It is present mainly in the Kinetoplastida but can be found in other parasitic protozoa such as ''

Entamoeba histolytica ''Entamoeba histolytica'' is an anaerobic organism, 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 mil ...

''. Since this thiol is absent from humans and is essential for the survival of the parasites, the

enzymes An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...

that make and use this molecule are targets for the development of new drugs to treat these diseases. Trypanothione-dependent enzymes include

reductase In biochemistry, an oxidoreductase is an enzyme that catalyzes the transfer of electrons from one molecule, the reductant, also called the electron donor, to another, the oxidant, also called the electron acceptor. This group of enzymes usually uti ...

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, and should not be confused with other ...

s, glyoxalases and

transferase In biochemistry, 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 ...

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 the R's represent a radical (a portion of a complete molecule; not necessarily a free radical) and O's are single oxygen atoms. Oxygen atoms are joined to each other and ...

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 viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...

metabolism is particularly important in these organisms because they lack

catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting ...

. 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. Bacterial 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