Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids
Chagas disease is caused by Trypanosoma cruzi and is endemic to North, Central and South American countries. Current therapy against this disease is only partially effective and produces adverse side effects. Studies on the metabolic pathways of T. cruzi, in particular those with no equivalent in ma...
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todo:paper_10665234_v58_n2_p79_DeLederkremer2023-10-03T16:02:09Z Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids De Lederkremer, R.M. Agusti, R. Docampo, R. Glycosylinositolphospholipids glycosylphosphatidylinositol inositolphosphoceramide phospholipase C sphingolipids Trypanosoma ceramide glycosphingolipid inositolphosphoceramides protozoal protein cell organelle drug endemic species enzyme activity fatty acid inhibition lipid mammal metabolism molecular analysis parasitic disease protein protozoan biosynthesis comparative study genetics Kinetoplastida metabolism review Trypanosoma cruzi Biosynthetic Pathways Ceramides Glycosphingolipids Protozoan Proteins Trypanosoma cruzi Trypanosomatina Kinetoplastida Mammalia Protista Trypanosoma Trypanosoma brucei Trypanosoma cruzi Trypanosomatidae Chagas disease is caused by Trypanosoma cruzi and is endemic to North, Central and South American countries. Current therapy against this disease is only partially effective and produces adverse side effects. Studies on the metabolic pathways of T. cruzi, in particular those with no equivalent in mammalian cells, might identify targets for the development of new drugs. Ceramide is metabolized to inositolphosphoceramide (IPC) in T. cruzi and other kinetoplastid protists whereas in mammals it is mainly incorporated into sphingomyelin. In T. cruzi, in contrast to Trypanosoma brucei and Leishmania spp., IPC functions as lipid anchor constituent of glycoproteins and free glycosylinositolphospholipids (GIPLs). Inhibition of IPC and GIPLs biosynthesis impairs differentiation of trypomastigotes into the intracellular amastigote forms. The gene encoding IPC synthase in T. cruzi has been identified and the enzyme has been expressed in a cell-free system. The enzyme involved in IPC degradation and the remodelases responsible for the incorporation of ceramide into free GIPLs or into the glycosylphosphatidylinositols anchoring glycoproteins, and in fatty acid modifications of these molecules of T. cruzi have been understudied. Inositolphosphoceramide metabolism and remodeling could be exploited as targets for Chagas disease chemotherapy. © 2011 The Author(s). Fil:De Lederkremer, R.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Agusti, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_10665234_v58_n2_p79_DeLederkremer |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Glycosylinositolphospholipids glycosylphosphatidylinositol inositolphosphoceramide phospholipase C sphingolipids Trypanosoma ceramide glycosphingolipid inositolphosphoceramides protozoal protein cell organelle drug endemic species enzyme activity fatty acid inhibition lipid mammal metabolism molecular analysis parasitic disease protein protozoan biosynthesis comparative study genetics Kinetoplastida metabolism review Trypanosoma cruzi Biosynthetic Pathways Ceramides Glycosphingolipids Protozoan Proteins Trypanosoma cruzi Trypanosomatina Kinetoplastida Mammalia Protista Trypanosoma Trypanosoma brucei Trypanosoma cruzi Trypanosomatidae |
| spellingShingle |
Glycosylinositolphospholipids glycosylphosphatidylinositol inositolphosphoceramide phospholipase C sphingolipids Trypanosoma ceramide glycosphingolipid inositolphosphoceramides protozoal protein cell organelle drug endemic species enzyme activity fatty acid inhibition lipid mammal metabolism molecular analysis parasitic disease protein protozoan biosynthesis comparative study genetics Kinetoplastida metabolism review Trypanosoma cruzi Biosynthetic Pathways Ceramides Glycosphingolipids Protozoan Proteins Trypanosoma cruzi Trypanosomatina Kinetoplastida Mammalia Protista Trypanosoma Trypanosoma brucei Trypanosoma cruzi Trypanosomatidae De Lederkremer, R.M. Agusti, R. Docampo, R. Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids |
| topic_facet |
Glycosylinositolphospholipids glycosylphosphatidylinositol inositolphosphoceramide phospholipase C sphingolipids Trypanosoma ceramide glycosphingolipid inositolphosphoceramides protozoal protein cell organelle drug endemic species enzyme activity fatty acid inhibition lipid mammal metabolism molecular analysis parasitic disease protein protozoan biosynthesis comparative study genetics Kinetoplastida metabolism review Trypanosoma cruzi Biosynthetic Pathways Ceramides Glycosphingolipids Protozoan Proteins Trypanosoma cruzi Trypanosomatina Kinetoplastida Mammalia Protista Trypanosoma Trypanosoma brucei Trypanosoma cruzi Trypanosomatidae |
| description |
Chagas disease is caused by Trypanosoma cruzi and is endemic to North, Central and South American countries. Current therapy against this disease is only partially effective and produces adverse side effects. Studies on the metabolic pathways of T. cruzi, in particular those with no equivalent in mammalian cells, might identify targets for the development of new drugs. Ceramide is metabolized to inositolphosphoceramide (IPC) in T. cruzi and other kinetoplastid protists whereas in mammals it is mainly incorporated into sphingomyelin. In T. cruzi, in contrast to Trypanosoma brucei and Leishmania spp., IPC functions as lipid anchor constituent of glycoproteins and free glycosylinositolphospholipids (GIPLs). Inhibition of IPC and GIPLs biosynthesis impairs differentiation of trypomastigotes into the intracellular amastigote forms. The gene encoding IPC synthase in T. cruzi has been identified and the enzyme has been expressed in a cell-free system. The enzyme involved in IPC degradation and the remodelases responsible for the incorporation of ceramide into free GIPLs or into the glycosylphosphatidylinositols anchoring glycoproteins, and in fatty acid modifications of these molecules of T. cruzi have been understudied. Inositolphosphoceramide metabolism and remodeling could be exploited as targets for Chagas disease chemotherapy. © 2011 The Author(s). |
| format |
JOUR |
| author |
De Lederkremer, R.M. Agusti, R. Docampo, R. |
| author_facet |
De Lederkremer, R.M. Agusti, R. Docampo, R. |
| author_sort |
De Lederkremer, R.M. |
| title |
Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids |
| title_short |
Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids |
| title_full |
Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids |
| title_fullStr |
Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids |
| title_full_unstemmed |
Inositolphosphoceramide metabolism in Trypanosoma cruzi as compared with other trypanosomatids |
| title_sort |
inositolphosphoceramide metabolism in trypanosoma cruzi as compared with other trypanosomatids |
| url |
http://hdl.handle.net/20.500.12110/paper_10665234_v58_n2_p79_DeLederkremer |
| work_keys_str_mv |
AT delederkremerrm inositolphosphoceramidemetabolismintrypanosomacruziascomparedwithothertrypanosomatids AT agustir inositolphosphoceramidemetabolismintrypanosomacruziascomparedwithothertrypanosomatids AT docampor inositolphosphoceramidemetabolismintrypanosomacruziascomparedwithothertrypanosomatids |
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1807323305354461184 |