The bis(glutathionyl)spermidine trypanothione exclusively
occurs in parasitic protozoa of the order Kinetoplastida,
such as trypanosomes and leishmania,
some of which are the causative agents of several
tropical diseases. The dithiol is kept reduced by the
flavoenzyme trypanothione reductase and the trypanothione
system replaces in these parasites the nearly
ubiquitous glutathione/glutathione reductase couple.
Trypanothione is a reductant of thioredoxin and tryparedoxin,
small dithiol proteins, which in turn deliver
reducing equivalents for the synthesis of deoxyribonucleotides
as well as for the detoxification of hydroperoxides
by different peroxidases. Depending on
the individual organism and the developmental state,
the parasites also contain significant amounts of glutathione,
mono-glutathionylspermidine and ovothiol,
whereby all four low molecular mass thiols are directly
(trypanothione and monoglutathionylspermidine)
or indirectly (glutathione and ovothiol) maintained in
the reduced state by trypanothione reductase. Thus
the trypanothione system is central for any thiol regeneration
and trypanothione reductase has been
shown to be an essential enzyme in these parasites.
The absence of this pathway from the mammalian
host and the sensitivity of trypanosomatids toward
oxidative stress render the enzymes of the trypanothione
metabolism attractive target molecules for the
rational development of new drugs against African
sleeping sickness, Chagas' disease and the different
forms of leishmaniasis.
Biological Chemistry keeps you up-to-date with the latest advances in the molecular life sciences. The journal publishes Research Articles, Short Communications, Reviews and Minireviews. Areas include: general biochemistry/pathobiochemistry, structural biology, molecular and cellular biology, genetics and epigenetics, virology, molecular medicine, plant molecular biology/biochemistry and novel experimental methodologies.