Acidification of the Malaria Parasites Digestive Vacuole by a H + -ATPase and a H + -pyrophosphatase

Date

2003

Authors

Saliba, Kevin
Allen, Richard
Zissis, S
Bray, Patrick
Ward, Stephen A
Kirk, Kiaran

Journal Title

Journal ISSN

Volume Title

Publisher

American Society for Biochemistry and Molecular Biology Inc

Abstract

As it grows within the human erythrocyte, the malaria parasite, Plasmodium falciparum, ingests the erythrocyte cytosol, depositing it via an endocytotic feeding mechanism in the "digestive vacuole," a specialized acidic organelle. The digestive vacuole is the site of hemoglobin degradation, the storage site for hemozoin (an inert biocrystal of toxic heme), the site of action of many antimalarial drugs, and the site of proteins known to be involved in antimalarial drug resistance. The acidic pH of this organelle is thought to play a critical role in its various functions; however, the mechanisms by which the pH within the vacuole is maintained are not well understood. In this study, we have used a combination of techniques to demonstrate the presence on the P. falciparum digestive vacuole membrane of two discrete H+ pumping mechanisms, both capable of acidifying the vacuole interior. One is a V-type H+-ATPase, sensitive to concanamycin A and bafilomycin A1. The other is a H+-pyrophosphatase, which was inhibited by NaF and showed a partial dependence on K+. The operation of the H+-pyrophosphatase was dependent on the presence of a Mg2+-pyrophosphate complex, and kinetic experiments gave results consistent with free pyrophosphate acting as an inhibitor of the protein. The presence of the combination of a H+-ATPase and a H+-pyrophosphatase on the P. falciparum digestive vacuole is similar to the situation in the acidic tonoplasts (vacuoles) of plant cells.

Description

Keywords

Keywords: Biochemistry; Biological membranes; Cells; Toxic materials; Acidification; Enzymes; antimalarial agent; bafilomycin A1; concanamycin A; hemoglobin; hemozoin; inorganic pyrophosphatase; proton transporting adenosine triphosphatase; inorganic pyrophosphatas

Citation

Source

Journal of Biological Chemistry

Type

Journal article

Book Title

Entity type

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DOI

10.1074/jbc.M208648200

Restricted until

2037-12-31