METABOLISM OF BABESIA PARASITES IN VITRO. AMINO ACID PRODUCTION BY BABESIA RODHAINI COMPARED TO PLASMODIUM BERGHEI

Barry, D. N.

doi:10.1038/icb.1982.18

Cited by 6 publications

(2 citation statements)

References 10 publications

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“…Second, the hemoglobin content of infected erythrocytes decreases 25-75% during the life cycle of erythrocytic parasites (2,3), and the concentration of free amino acids is greater in infected erythrocytes than in uninfected erythrocytes (4). Third, the composition of the amino acid pool of infected erythrocytes is similar to the amino acid composition of hemoglobin (5)(6)(7). Fourth, the infection of erythrocytes containing radiolabeled hemoglobin is followed by the appearance of labeled amino acids in parasite proteins (8)(9)(10).…”

mentioning

confidence: 82%

A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum.

Rosenthal

McKerrow²,

Aikawa³

et al. 1988

J. Clin. Invest.

317

231

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To obtain free amino acids for protein synthesis, trophozoite stage malaria parasites feed on the cytoplasm of host erythrocytes and degrade hemoglobin within an acid food vacuole. The food vacuole appears to be analogous to the secondary lysosomes of mammalian cells. To determine the enzymatic mechanism of hemoglobin degradation, we incubated trophozoite-infected erythrocytes with peptide inhibitors of different classes of proteinases. Leupeptin and L-transepoxy-succinyl-leucylamido-(4-guanidino)-butane (E-64) sufficient for the needs of the parasite (1). Second, the hemoglobin content of infected erythrocytes decreases 25-75% during the life cycle of erythrocytic parasites (2,3), and the concentration of free amino acids is greater in infected erythrocytes than in uninfected erythrocytes (4). Third, the composition of the amino acid pool of infected erythrocytes is similar to the amino acid composition of hemoglobin (5-7). Fourth, the infection of erythrocytes containing radiolabeled hemoglobin is followed by the appearance of labeled amino acids in parasite proteins (8-10).Hemoglobin degradation occurs predominantly during the trophozoite stage ofthe erythrocytic life cycle ofP. falciparum. Trophozoites ingest erythrocyte cytoplasm and transport it within vesicles to a large central food vacuole (1 1, 12), where the hemoglobin-rich cytoplasm is degraded. In the food vacuole the heme moiety precipitates and is a major component of malarial pigment (13), and globin is hydrolyzed to its constituent free amino acids. The food vacuole of P. falciparum is an acidic (14, 15), membrane-bound (1 1) compartment where proteins are degraded, and therefore it appears to be analogous to the secondary lysosomes of mammalian cells, where multiple proteinases hydrolyze proteins at acid pH (16,17).The enzymatic mechanism of globin degradation within the malarial food vacuole is unknown. In previous studies, aspartic proteinases that degraded denatured hemoglobin were isolated from malaria parasites (18-20). However, denatured hemoglobin is a nonspecific substrate that can be hydrolyzed by many proteinases, and the biological role of the aspartic proteinases cannot be determined from these studies. To determine the enzymatic mechanism of globin degradation in the trophozoite food vacuole we first studied the effects of class-specific proteinase inhibitors on intact parasites. We found that two peptide inhibitors of cysteine proteinases blocked globin degradation in the food vacuole of P. falciparum trophozoites. We also identified a cysteine proteinase of trophozoites that was inhibited by the same two proteinase inhibitors and had biochemical properties that were similar to those of the lysosomal cysteine proteinase cathepsin L. Our results suggest that the cysteine proteinase we identified has a critical role in hemoglobin degradation in the food vacuole of P. falciparum trophozoites.

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mentioning

confidence: 82%

A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum.

Rosenthal

McKerrow²,

Aikawa³

et al. 1988

J. Clin. Invest.

317

231

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“…Amino acids were shown to be essential nutritional requirements of the parasite a century ago [3]. For example, the severity of malaria is related to arginine concentration in plasma and L-arginine administration to cerebral malaria patients reverts endothelial dysfunction [4,5].…”

Section: Introductionmentioning

confidence: 99%

Multivariable analysis of host amino acids in plasma and liver during infection of malaria parasite Plasmodium yoelii

Saiki

Nagao

Aonuma

et al. 2013

Malar J

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BackgroundMalaria is the most significant human parasitic disease, and yet understanding of the energy metabolism of the principle pathogen, Plasmodium falciparum, remains to be fully elucidated. Amino acids were shown to be essential nutritional requirements since early times and much of the current knowledge of Plasmodium energy metabolism is based on early biochemical work, performed using basic analytical techniques, carried out almost exclusively on human plasma with considerable inter-individual variability.MethodsIn order to further characterize the fate of amino acid metabolism in malaria parasite, multivariate analysis using statistical modelling of amino acid concentrations (aminogram) of plasma and liver were determined in host infected with rodent malaria parasite, Plasmodium yoelii.Results and conclusionComprehensive and statistical aminogram analysis revealed that P. yoelii infection caused drastic change of plasma and liver aminogram, and altered intra- and inter-correlation of amino acid concentration in plasma and liver. These findings of the interactions between amino acids and Plasmodium infection may provide insight to reveal the interaction between nutrients and parasites.

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Digestion of the host erythrocyte by malaria parasites is the primary target for quinolinecontaining antimalarials

Zarchin

Krugliak

Ginsburg

1986

Biochemical Pharmacology

105

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METABOLISM OF BABESIA PARASITES IN VITRO. AMINO ACID PRODUCTION BY BABESIA RODHAINI COMPARED TO PLASMODIUM BERGHEI

Cited by 6 publications

References 10 publications

A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum.

A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum.

Multivariable analysis of host amino acids in plasma and liver during infection of malaria parasite Plasmodium yoelii

Digestion of the host erythrocyte by malaria parasites is the primary target for quinolinecontaining antimalarials

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