Related Experiment Video
Updated: Jun 18, 2026
14:26
Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers (Diethylaminoethyl-cellulose Columns)
Published on: April 6, 2019
Trypanothione efficiently intercepts nitric oxide as a harmless iron complex in trypanosomatid parasites
Alessio Bocedi1, Kutayba F Dawood, Raffaele Fabrini
1Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, via della Ricerca Scientifica 1, 00133 Rome, Italy.
Summary
Trypanosomatid parasites utilize trypanothione (T(SH)(2)) to effectively neutralize harmful nitric oxide and iron. This unique defense mechanism, unlike in mammalian cells, prevents enzyme inactivation and explains T(SH)(2)
Area of Science:
- Parasitology
- Biochemistry
- Molecular Biology
Background:
- Trypanosomatids cause significant human diseases like sleeping sickness and leishmaniasis.
- These parasites uniquely use trypanothione (T(SH)(2)) instead of glutathione (GSH) for redox balance.
- The biological role of T(SH)(2) in parasites has been an ongoing scientific question.
Purpose of the Study:
- To investigate the function of trypanothione (T(SH)(2)) in trypanosomatid parasites.
- To determine the interaction of T(SH)(2) with nitric oxide (NO) and iron.
- To compare the protective mechanisms of T(SH)(2) in parasites with glutathione (GSH) in mammalian cells.
Main Methods:
- Studied the binding affinity of T(SH)(2) and GSH to nitric oxide and iron.
- Observed the formation of dinitrosyl-iron complexes in vivo in Trypanosoma brucei and Leishmania infantum.
- Assessed the inhibitory effects of these complexes on trypanothione reductase (TR) and glutathione reductase (GR).
Main Results:
- T(SH)(2) binds nitric oxide and iron with significantly higher affinity (over 600x) than GSH.
- Paramagnetic dinitrosyl-trypanothionyl iron complexes were detected in NO-exposed parasites.
- The T(SH)(2)-iron complex did not inhibit TR, unlike the GSH-iron complex which inhibited GR.
Conclusions:
- T(SH)(2) efficiently sequesters nitric oxide and iron into a stable, harmless complex in trypanosomatids.
- This unique biochemical pathway explains T(SH)(2)'s prevalence in parasites exposed to NO.
- The findings offer insights into parasite survival mechanisms and potential therapeutic targets.
Related Concept Videos
01:21Antiprotozoal Agents
Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...
01:22American Trypanosomiasis
Chagas disease, or American trypanosomiasis, is a vector-borne parasitic infection caused by Trypanosoma cruzi, a flagellated protozoan (kinetoplastid) of the family Trypanosomatidae. The disease is endemic in Latin America, although cases are increasingly reported worldwide due to human migration. Transmission most commonly occurs when feces of infected triatomine bugs contaminate bite wounds or mucosal surfaces; additional routes include congenital, transfusional, transplant-related, and oral...
01:30The Electron Transport Chain
The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
01:15Anthelminthic Agents
Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
01:28Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
01:202° Amines to N-Nitrosamines: Reaction with NaNO2
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.