Porphyrin biosynthesis in parasitic hemoflagellates: Functional and defective enzymes in Trypanosoma cruzi

1. 1. Heme compounds are necessary as a growth factor for Trypanosoma cruzi in culture, this porphyrin requirement being due to the inability of the parasite to synthesize heme. To obtain supporting evidence for this hypothesis, an extensive study of porphyrin biosynthesis in the epimastogote form o...

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Detalles Bibliográficos
Autores principales: Salzman, T.A., Stella, A.M., Wider de Xifra, E.A., Batlle, A.M.D.C., Docampo, R., Stoppani, A.O.M.
Formato: JOUR
Materias:
5 aminolevulinate synthase
aminolevulinate aminotransferase
aminotransferase
ammonia lyase
Ammonia Lyases
ferrochelatase
heme
porphobilinogen synthase
porphyrin
Succinate CoA Ligases
succinyl coenzyme A synthetase
animal
article
biosynthesis
enzymology
metabolism
Trypanosoma cruzi
5-Aminolevulinate Synthetase
Ammonia-Lyases
Animal
Ferrochelatase
Heme
Porphobilinogen Synthase
Porphyrins
Succinate-CoA Ligases
Support, Non-U.S. Gov't
Transaminases
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_03050491_v72_n4_p663_Salzman
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:1. 1. Heme compounds are necessary as a growth factor for Trypanosoma cruzi in culture, this porphyrin requirement being due to the inability of the parasite to synthesize heme. To obtain supporting evidence for this hypothesis, an extensive study of porphyrin biosynthesis in the epimastogote form of T. cruzi (Tulahuén strain) was carried out. 2. 2. Low levels of endogenous δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) were found in extracts of T. cruzi. Free porphyrins and heme contents were practically nil. 3. 3. The activity of succinyl CoA synthetase (Suc, CoA-S) was rather high and therefore non-limiting. 4. 4. Both δ-aminolevulinic acid synthetase (ALA-S) and 4,5, dioxovaleric transaminase (DOVA-T), the two enzymes forming ALA, were readily detected and their activities, although low, were of the same order. 5. 5. δ-Aminolevulinic acid dehydratase (ALA-D) activity was almost negligible and both porphobilinogenase (PBGase) and deaminase were absent or inactive. 6. 6. Heme-Synthetase (Heme-S) was totally functional. 7. 7. It is concluded that T. cruzi has lost part of its heme biosynthetic pathway, possibly due to mutations of several genes involved in the synthesis of the soluble enzymes ALA-D, PBGase, deaminase and probably others preceding Heme-S; while the particulate enzymes Suc CoA-S, ALA-S, DOVA-T and Heme-S are functional. As a consequence, the host should supply the parasite with the porphyrin substrate to form its essential heme compounds. © 1982.

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