5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi

Background and aims: Trypanosoma cruzi is the causative agent of Chagas disease or American trypanosomiasis. The parasite manifests a nutritional requirement for heme compounds because of its biosynthesis deficiency. The aim of this study has been to investigate the presence of metabolites and enzym...

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Autores principales:	Lombardo, María Elisa, Araujo, Lidia Susana, Batlle, Alcira María del Carmen
Publicado:	2003
Materias:	5-Aminolevulinic acid 5-Aminolevulinic acid synthetase inhibition Heme synthesis Trypanosoma cruzi 4,5 dioxovaleric transaminase 5 aminolevulinate synthase aminolevulinic acid aminotransferase bacterial enzyme heme porphobilinogen porphobilinogen synthase porphyrin porphyrin derivative succinyl coenzyme A synthetase unclassified drug amino acid metabolism article cell free system cytotoxicity enzyme activity epimastigote metabolite molecular weight nonhuman synthesis thermostability Bacteria (microorganisms) Trypanosoma
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v35_n8_p1263_Lombardo http://hdl.handle.net/20.500.12110/paper_13572725_v35_n8_p1263_Lombardo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_13572725_v35_n8_p1263_Lombardo2023-06-08T16:11:17Z 5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi Lombardo, María Elisa Araujo, Lidia Susana Batlle, Alcira María del Carmen 5-Aminolevulinic acid 5-Aminolevulinic acid synthetase inhibition Heme synthesis Trypanosoma cruzi 4,5 dioxovaleric transaminase 5 aminolevulinate synthase aminolevulinic acid aminotransferase bacterial enzyme heme porphobilinogen porphobilinogen synthase porphyrin porphyrin derivative succinyl coenzyme A synthetase unclassified drug amino acid metabolism article cell free system cytotoxicity enzyme activity epimastigote metabolite molecular weight nonhuman synthesis thermostability Trypanosoma cruzi Bacteria (microorganisms) Trypanosoma Trypanosoma cruzi Trypanosoma cruzi Background and aims: Trypanosoma cruzi is the causative agent of Chagas disease or American trypanosomiasis. The parasite manifests a nutritional requirement for heme compounds because of its biosynthesis deficiency. The aim of this study has been to investigate the presence of metabolites and enzymes of porphyrin pathway, as well as ALA formation in epimastigotes of T. cruzi, Tulahuén strain, Tul 2 stock. Methods: Succinyl CoA synthetase, 5-aminolevulinic acid (ALA) synthetase, 4,5-dioxovaleric (DOVA) transaminase, ALA dehydratase and porphobilinogenase activities, as well as ALA, porphobilinogen (PBG), free porphyrins and heme content were measured in a parasite cells-free extract. Extracellular content of these metabolites was also determined. Results: DOVA, PBG, porphyrins and heme were not detected in acellular extracts of T. cruzi. However ALA was detected both intra- and extracellularly This is the first time that the presence of ALA (98% of intracellularly formed ALA) is demonstrated in the extracellular medium of a parasite culture. Regarding the ALA synthesizing enzymes, DOVA transaminase levels found were low (7.13±0.49EU/mg protein), whilst ALA synthetase (ALA-S) activity was undetectable. A compound of non-protein nature, low molecular weight, heat unstable, inhibiting bacterial ALA-S activity was detected in an acellular extract of T. cruzi. This inhibitor could not be identified with either ALA, DOVA or heme. Conclusions: ALA synthesis is functional in the parasite and it would be regulated by the heme levels, both directly and through the inhibitor factor detected. ALA formed can not be metabolized further, because the necessary enzymes are not active, therefore it should be excreted to avoid intracellular cytotoxicity. © 2003 Elsevier Science Ltd. All rights reserved. Fil:Lombardo, M.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Araujo, L.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2003 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v35_n8_p1263_Lombardo http://hdl.handle.net/20.500.12110/paper_13572725_v35_n8_p1263_Lombardo
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	5-Aminolevulinic acid 5-Aminolevulinic acid synthetase inhibition Heme synthesis Trypanosoma cruzi 4,5 dioxovaleric transaminase 5 aminolevulinate synthase aminolevulinic acid aminotransferase bacterial enzyme heme porphobilinogen porphobilinogen synthase porphyrin porphyrin derivative succinyl coenzyme A synthetase unclassified drug amino acid metabolism article cell free system cytotoxicity enzyme activity epimastigote metabolite molecular weight nonhuman synthesis thermostability Trypanosoma cruzi Bacteria (microorganisms) Trypanosoma Trypanosoma cruzi Trypanosoma cruzi
spellingShingle	5-Aminolevulinic acid 5-Aminolevulinic acid synthetase inhibition Heme synthesis Trypanosoma cruzi 4,5 dioxovaleric transaminase 5 aminolevulinate synthase aminolevulinic acid aminotransferase bacterial enzyme heme porphobilinogen porphobilinogen synthase porphyrin porphyrin derivative succinyl coenzyme A synthetase unclassified drug amino acid metabolism article cell free system cytotoxicity enzyme activity epimastigote metabolite molecular weight nonhuman synthesis thermostability Trypanosoma cruzi Bacteria (microorganisms) Trypanosoma Trypanosoma cruzi Trypanosoma cruzi Lombardo, María Elisa Araujo, Lidia Susana Batlle, Alcira María del Carmen 5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi
topic_facet	5-Aminolevulinic acid 5-Aminolevulinic acid synthetase inhibition Heme synthesis Trypanosoma cruzi 4,5 dioxovaleric transaminase 5 aminolevulinate synthase aminolevulinic acid aminotransferase bacterial enzyme heme porphobilinogen porphobilinogen synthase porphyrin porphyrin derivative succinyl coenzyme A synthetase unclassified drug amino acid metabolism article cell free system cytotoxicity enzyme activity epimastigote metabolite molecular weight nonhuman synthesis thermostability Trypanosoma cruzi Bacteria (microorganisms) Trypanosoma Trypanosoma cruzi Trypanosoma cruzi
description	Background and aims: Trypanosoma cruzi is the causative agent of Chagas disease or American trypanosomiasis. The parasite manifests a nutritional requirement for heme compounds because of its biosynthesis deficiency. The aim of this study has been to investigate the presence of metabolites and enzymes of porphyrin pathway, as well as ALA formation in epimastigotes of T. cruzi, Tulahuén strain, Tul 2 stock. Methods: Succinyl CoA synthetase, 5-aminolevulinic acid (ALA) synthetase, 4,5-dioxovaleric (DOVA) transaminase, ALA dehydratase and porphobilinogenase activities, as well as ALA, porphobilinogen (PBG), free porphyrins and heme content were measured in a parasite cells-free extract. Extracellular content of these metabolites was also determined. Results: DOVA, PBG, porphyrins and heme were not detected in acellular extracts of T. cruzi. However ALA was detected both intra- and extracellularly This is the first time that the presence of ALA (98% of intracellularly formed ALA) is demonstrated in the extracellular medium of a parasite culture. Regarding the ALA synthesizing enzymes, DOVA transaminase levels found were low (7.13±0.49EU/mg protein), whilst ALA synthetase (ALA-S) activity was undetectable. A compound of non-protein nature, low molecular weight, heat unstable, inhibiting bacterial ALA-S activity was detected in an acellular extract of T. cruzi. This inhibitor could not be identified with either ALA, DOVA or heme. Conclusions: ALA synthesis is functional in the parasite and it would be regulated by the heme levels, both directly and through the inhibitor factor detected. ALA formed can not be metabolized further, because the necessary enzymes are not active, therefore it should be excreted to avoid intracellular cytotoxicity. © 2003 Elsevier Science Ltd. All rights reserved.
author	Lombardo, María Elisa Araujo, Lidia Susana Batlle, Alcira María del Carmen
author_facet	Lombardo, María Elisa Araujo, Lidia Susana Batlle, Alcira María del Carmen
author_sort	Lombardo, María Elisa
title	5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi
title_short	5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi
title_full	5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi
title_fullStr	5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi
title_full_unstemmed	5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi
title_sort	5-aminolevulinic acid synthesis in epimastigotes of trypanosoma cruzi
publishDate	2003
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13572725_v35_n8_p1263_Lombardo http://hdl.handle.net/20.500.12110/paper_13572725_v35_n8_p1263_Lombardo
work_keys_str_mv	AT lombardomariaelisa 5aminolevulinicacidsynthesisinepimastigotesoftrypanosomacruzi AT araujolidiasusana 5aminolevulinicacidsynthesisinepimastigotesoftrypanosomacruzi AT batllealciramariadelcarmen 5aminolevulinicacidsynthesisinepimastigotesoftrypanosomacruzi
_version_	1768546267640627200

5-Aminolevulinic acid synthesis in epimastigotes of Trypanosoma cruzi

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