Transsulfuration is an active pathway for cysteine biosynthesis in Trypanosoma rangeli

Particle and Fibre Toxicology

Edmundo Carlos Grisard¹  Alvaro José Romanha²  Mario Steindel¹  Lais Eiko Yamanaka¹  Jair Téllez¹  Ibeth Romero¹ 

[1]Laboratórios de Protozoologia e de Bioinformática, Departamento de Microbiologia, Imunologia e Parasitologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-970, Brasil

[2]Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, MG, Brasil

关键词: Antioxidant defence;    Thiol metabolism;    T. rangeli;    Cysteine synthase;    Cystathionine β-synthase;    Cysteine biosynthesis;   

Others  :  807094
DOI  :  10.1186/1756-3305-7-197

 received in 2013-12-19, accepted in 2014-04-15,  发布年份 2014

【 摘 要 】

Background

Cysteine, a sulfur-containing amino acid, plays an important role in a variety of cellular functions such as protein biosynthesis, methylation, and polyamine and glutathione syntheses. In trypanosomatids, glutathione is conjugated with spermidine to form the specific antioxidant thiol trypanothione (T[SH]₂) that plays a central role in maintaining intracellular redox homeostasis and providing defence against oxidative stress.

Methods

We cloned and characterised genes coding for a cystathionine β-synthase (CβS) and cysteine synthase (CS), key enzymes of the transsulfuration and assimilatory pathways, respectively, from the hemoflagellate protozoan parasite Trypanosoma rangeli.

Results

Our results show that T. rangeli CβS (TrCβS), similar to its homologs in T. cruzi, contains the catalytic domain essential for enzymatic activity. Unlike the enzymes in bacteria, plants, and other parasites, T. rangeli CS lacks two of the four lysine residues (Lys²⁶ and Lys¹⁸⁴) required for activity. Enzymatic studies using T. rangeli extracts confirmed the absence of CS activity but confirmed the expression of an active CβS. Moreover, CβS biochemical assays revealed that the T. rangeli CβS enzyme also has serine sulfhydrylase activity.

Conclusion

These findings demonstrate that the RTS pathway is active in T. rangeli, suggesting that this may be the only pathway for cysteine biosynthesis in this parasite. In this sense, the RTS pathway appears to have an important functional role during the insect stage of the life cycle of this protozoan parasite.

【 授权许可】

   
2014 Romero et al.; licensee BioMed Central Ltd.

【 图 表 】

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