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Tocopherol biosynthesis in Leishmania (L.) amazonensis promastigotes
- Source :
- FEBS Open Bio
- Publication Year :
- 2019
- Publisher :
- John Wiley and Sons Inc., 2019.
-
Abstract
- Leishmaniasis is a neglected disease caused by a trypanosomatid protozoan of the genus Leishmania. Most drugs used to treat leishmaniasis are highly toxic, and the emergence of drug-resistant strains has been observed. Therefore, new therapeutic targets against leishmaniasis are required. Several isoprenoid compounds, including dolichols or ubiquinones, have been shown to be important for cell viability and proliferation in various trypanosomatid species. Here, we detected the biosynthesis of tocopherol in Leishmania (L.) amazonensis promastigotes in vitro through metabolic labelling with [1-(n)-3H]-phytol. Subsequently, we confirmed the presence of vitamin E in the parasite by gas chromatography-mass spectrometry. Treatment with usnic acid or nitisinone, inhibitors of precursors of vitamin E synthesis, inhibited growth of the parasite in a concentration-dependent manner. This study provides the first evidence of tocopherol biosynthesis in a trypanosomatid and suggests that inhibitors of the enzyme 4-hydroxyphenylpyruvate dioxygenase may be suitable for use as antileishmanial compounds. Database The amino acid sequence of a conserved hypothetical protein [Leishmania mexicana MHOM/GT/2001/U1103] has been deposited in GenBank (CBZ28005.1).
- Subjects :
- 0301 basic medicine
Leishmania (L.) amazonensis
Hypothetical protein
Tocopherols
trypanosomatid
4-Hydroxyphenylpyruvate Dioxygenase
General Biochemistry, Genetics and Molecular Biology
Leishmania mexicana
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Biosynthesis
parasitic diseases
medicine
Tocopherol
Enzyme Inhibitors
Research Articles
Benzofurans
chemistry.chemical_classification
Leishmania
nitisinone, tocopherol
biology
isoprenoid
Cyclohexanones
usnic acid
Usnic acid
Leishmaniasis
medicine.disease
biology.organism_classification
030104 developmental biology
Enzyme
chemistry
Biochemistry
030220 oncology & carcinogenesis
Nitrobenzoates
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 22115463
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- FEBS Open Bio
- Accession number :
- edsair.doi.dedup.....48eeff7de698bfb0d03dfb6a422f8afe