Heme synthetase in Trypanosoma cruzi.
Heme-synthetase (Heme-S) has been studied in the epimastigote form of T. cruzi (Tulahuen and Y strains). The enzyme is confined to the "mitochondrial" fraction (sedimented at 30,000 g). Activity was dependent on protein and time of cell storage. Enzymic proto- and meso-heme formation was inhibited up to 40 and 72% respectively by Triton X-100. The optimum pH was 7.2 for protoheme and 7.5 for mesoheme formation. Heme-S reached its maximum when the concentration values were 37; 35 and 32 microM for proto-, meso-, and deuteroporphyrin, respectively. The activity is several times higher when mesoporphyrin is used as substrate. At a final conc of 100 microM Fe2+ and Zn2+ ions enhanced activity 200-400%. Cu2+ and Co2+ had no effect, while Mn2+ and Mg2+ were highly inhibitory. A combination of Fe2+ and Zn2+ at varying concentrations still showed great activation. However, at a fixed level of Fe2+, Cu2+ was changed into a strong inhibitor. We propose that, if it can be demonstrated that T. cruzi cannot multiply when protoheme is replaced by mesoheme, administration of mesoporphyrin would then greatly affect replication of T. cruzi. Furthermore, the addition of certain metals, such as Cu2+ to T. cruzi cultures might specifically inhibit the parasite enzyme opening the possibility of selectively destroying the hemoflagellate without affecting the host.
D000818:Animals; D002413:Cations, Divalent; D005294:Ferrochelatase / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D008190:Lyases / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology; D013347:Subcellular Fractions / Q000201:enzymology; D014349:Trypanosoma cruzi / Q000201:enzymology*
D002413:Cations, Divalent; D007501:Iron; D008190:Lyases; D005294:Ferrochelatase