The metabolism of <i>Plasmodium berghei</i>, the malaria parasite of rodents. 2. An effect of mepacrine on the metabolism of glucose by the parasite separated from its host cell

Bowman, I.B.R.; Grant, P. T.; Kermack, W. O.; Ogston, D.

doi:10.1042/bj0780472

Cited by 62 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the mitochondria of asexual Plasmodium parasites, however, the electron transport chain is not a primary source of ATP and the parasite instead relies on glycolysis for most of its ATP production (107). Indeed, little of the parasitic glucose supply is completely oxidized, and glucose is instead excreted as lactic acid (108,109). Additionally, the parasites show relatively little oxygen consumption, consistent with minimal respiration (110).…”

Section: Coenzyme Q (Ubiquinone)mentioning

confidence: 95%

Isoprenoid Biosynthesis in Plasmodium falciparum

2014

View full text Add to dashboard Cite

bMalaria kills nearly 1 million people each year, and the protozoan parasite Plasmodium falciparum has become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis in P. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. In P. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis in P. falciparum has been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis in P. falciparum, in order to identify valuable directions for future research.

show abstract

Section: Coenzyme Q (Ubiquinone)mentioning

confidence: 95%

Isoprenoid Biosynthesis in Plasmodium falciparum

2014

View full text Add to dashboard Cite

show abstract

“…CS P. berghei converts glucose to lactate by anaerobic glycolysis (18)(19)(20)(21), consumes oxygen (18,19), and presumably conserves energy liberated by electron transport (22), although it does not have a well-defined mitochondrion (23). Apparently it does not have a functional citric acid cycle (24).…”

Section: Discussionmentioning

confidence: 99%

High-Affinity Accumulation of Chloroquine by Mouse Erythrocytes Infected with Plasmodium berghei

Fitch¹,

Yunis²,

Chevli³

et al. 1974

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Washed erythrocytes infected with chloroquine-susceptible (CS) or with chloroquine-resistant (CR) P. berghei were used in model systems in vitro to study the accumulation of chloroquine with high affinity. The CS model could achieve distribution ratios (chloroquine in cells: chloroquine in medium) of 100 in the absence of substrate, 200-300 in the presence of 10 mM pyruvate or lactate, and over 600 in the presence of 1 mM glucose or glycerol. In comparable studies of the CR model, the distribution ratios were 100 in the absence of substrate and 300 or less in the presence of glucose or glycerol. The presence of lactate stimulated chloroquine accumulation in the CR model, whereas the presence of pyruvate did not. Lactate production from glucose and glycerol was undiminished in the CR model, and ATP concentrations were higher than in the CS model. Cold, iodoacetate, 2,4-dinitrophenol, or decreasing pH inhibited chloroquine accumulation in both models. These findings demonstrate substrate involvement in the accumulation of chloroquine with high affinity.In studies of the CS model, certain compounds competitively inhibited chloroquine accumulation, while others did not. This finding is attributable to a specific receptor that imposes structural constraints on the process of accumulation. For chloroquine analogues, the position and length of the side chain, the terminal nitrogen atom of the side chain, and the nitrogen atom in the quinoline ring are important determinants of binding to this receptor.

show abstract

“…This glucose consumption contrasts with the >90% glucose-to-lactate conversion observed in uninfected RBCs and reflects the increased flux of glucose carbon into biomass (nucleic acids, lipids, glycosylated proteins) required for proliferating parasites. Only a very small fraction of the total glucose is completely oxidized to carbon dioxide, at least in mammalian malaria parasites [1, 18, 19], which has generally been taken to indicate the absence of a functional citric acid cycle contributing to energy generation. This is in keeping with the observation that in vitro cultures of P. falciparum exhibit only minimal oxygen consumption [20] (and in fact prefer microaerophilic conditions of ~5% oxygen, being growth-inhibited by normal atmospheric oxygen concentrations [21]. )…”

Section: Glycolysismentioning

confidence: 99%

Central carbon metabolism of Plasmodium parasites

Olszewski

Llinás

2011

Molecular and Biochemical Parasitology

View full text Add to dashboard Cite

The central role of metabolic perturbation to the pathology of malaria, the promise of antimetabolites as antimalarial drugs and a basic scientific interest in understanding this fascinating example of highly divergent microbial metabolism has spurred a major and concerted research effort towards elucidating the metabolic network of the Plasmodium parasites. Central carbon metabolism, broadly comprising the flow of carbon from nutrients into biomass, has been a particular focus due to clear and early indications that it plays an essential role in this network. Decades of painstaking efforts have significantly clarified our understanding of these pathways of carbon flux, and this foundational knowledge, coupled with the advent of advanced analytical technologies, have set the stage for the development of a holistic, network-level model of plasmodial carbon metabolism. In this review we summarize the current state of knowledge regarding central carbon metabolism and suggest future avenues of research. We focus primarily on the blood stages of Plasmodium falciparum, the most lethal of the human malaria parasites, but also integrate results from simian, avian and rodent models of malaria that were a major focus of early investigations into plasmodial metabolism.

show abstract

The metabolism of Plasmodium berghei, the malaria parasite of rodents. 2. An effect of mepacrine on the metabolism of glucose by the parasite separated from its host cell

Cited by 62 publications

References 18 publications

Isoprenoid Biosynthesis in Plasmodium falciparum

Isoprenoid Biosynthesis in Plasmodium falciparum

High-Affinity Accumulation of Chloroquine by Mouse Erythrocytes Infected with Plasmodium berghei

Central carbon metabolism of Plasmodium parasites

Contact Info

Product

Resources

About