Transport of lactate in Plasmodium falciparum-infected human erythrocytes.
The intraerythrocytic human malarial parasite Plasmodium falciparum produces lactate at a rate that exceeds the maximal capacity of the normal red cell membrane to transport lactate. In order to establish how the infected cell removes this excess lactate, the transport of lactate across the host cell and the parasite membranes has been investigated. Transport of radiolabeled L-lactate across the host cell membrane was shown to increase ca. 600-fold compared to uninfected erythrocytes. It showed no saturation with [L-lactate] and was inhibited by inhibitors of the monocarboxylate carrier, cinnamic acid derivatives (CADs), but not by the SH-reagent p-chloromercuriphenyl sulfonic acid (PCMBS). These results suggest that L-lactate is translocated through CAD-inhibitable new pathways induced in the host cell membrane by parasite activity, probably by diffusion of the acid form and through a modified native monocarboxylate:H+ symporter. Continuous monitoring of extracellular pH changes occurring upon suspension of infected cells in isoosmotic Na-lactate solutions indicates that part of the lactate egress is mediated by anionic exchange through the constitutive, but modified, anion exchanger. The transport of L-lactate across the parasite membrane is rapid, nonsaturating, and insensitive to either CADs or PCMBS, or to the presence of pyruvate. L-lactate uptake increased transiently when external pH was lowered and decreased when delta pH was dissipated by the protonophore carbonylcyanide m-chlorophenyl hydrazone (CCCP). These results are compatible with L-lactate crossing the parasite membrane either as the undissociated acid or by means of a novel type of lactate-/H+ symport.
Kanaani
J
J
Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
Ginsburg
H
H
D002731:4-Chloromercuribenzenesulfonate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D007773:Lactates / Q000097:blood*; D016778:Malaria, Falciparum / Q000097:blood*; D010963:Plasmodium falciparum / Q000502:physiology
D002934:Cinnamates; D007773:Lactates; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D002731:4-Chloromercuribenzenesulfonate