Saturday, January 15, 2011

What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2011 Jan 15
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results
Items 1 - 2 of 2

1. Int J Parasitol. 2011 Jan 10. [Epub ahead of print]

Inhibition profile of Leishmania mexicana arginase reveals differences with human arginase I.

Riley E, Roberts SC, Ullman B.

Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Rd., Portland, OR, 97239-3098 USA.

Abstract

Arginase (ARG), the enzyme that catalyzes the conversion of arginine to ornithine and urea, is the first and committed step in polyamine biosynthesis in Leishmania. The creation of a conditionally lethal Δarg null mutant in Leishmania mexicana has established that ARG is an essential enzyme for the promastigote form of the parasite and that the enzyme provides an important defense mechanism for parasite survival in the eukaryotic host. Furthermore, human ARGI (HsARGI) has also been implicated as a key factor in parasite proliferation. Thus, inhibitors of ARG offer a rational paradigm for drug design. To initiate a search for inhibitors of the L. mexicana ARG (LmARG), recombinant LmARG and HsARGI enzymes were purified from Escherichia coli. Both LmARG and HsARGI were specific for L-arginine and exhibited no activity with either D-arginine or agmatine as possible substrates. LmARG exhibited a K(m) of 25 ± 4 mM for L-arginine, a pH optimum ∼9.0, and was dependent upon the presence of a divalent cation, preferentially manganese. A K(m) of 13.5 ± 2 mM for L-arginine was calculated for the HsARGI. A collection of 37 compounds was evaluated against both enzymes. Twelve of these compounds were identified as being either strong inhibitors of both LmARG and HsARGI or differential inhibitors between the two enzymes. Of the 12 compounds, six were selected for further analysis and the type and extent of inhibition determined.

Copyright © 2011. Published by Elsevier Ltd.
PMID: 21232540 [PubMed - as supplied by publisher]
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2. FEBS J. 2011 Jan 13. doi: 10.1111/j.1742-4658.2011.08012.x. [Epub ahead of print]

Trypanosoma brucei: a model microorganism to study eukaryotic phospholipid biosynthesis.

Serricchio M, Bütikofer P.

Institute of Biochemistry & Molecular Medicine, University of Bern, Bern, Switzerland.

Abstract

Although the protozoan parasite, Trypanosoma brucei, can acquire lipids from its environment, recent reports have shown that it is also capable of de novo synthesis of all major phospholipids. In this paper, we provide an overview of the biosynthetic pathways involved in phospholipid formation in T. brucei and highlight differences to corresponding pathways in other eukaryotes, with the aim to promote trypanosomes as an attractive model organism to study lipid biosynthesis. We review that de novo synthesis of phosphatidylethanolamine involving CDP-activated intermediates is essential in T. brucei and that a reduction in its cellular content affects mitochondrial morphology and ultrastructure. In addition, we highlight that reduced levels of phosphatidylcholine inhibit nuclear division, suggesting a role for PC formation in the control of cell division. Furthermore, we discuss possible routes leading to phosphatidylserine and cardiolipin formation in T. brucei and review the biosynthesis of phosphatidylinositol, which seems to take place in two separate compartments. Finally, we emphasize that T. brucei represents the only eukaryote so far that synthesizes all three sphingophospholipid classes, sphingomyelin, inositolphosphorylceramide and ethanolaminephosphorylceramide, and that their production is developmentally regulated.

Journal compilation © 2011 Federation of European Biochemical Societies.
PMID: 21232016 [PubMed - as supplied by publisher]
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