Exploiting Amino acid Structure to Learn About Membrane Transport

Christensen, Halvor N.

doi:10.1002/9780470122945.ch2

Cited by 109 publications

(5 citation statements)

References 185 publications

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“…Fig. 1B illustrates the effects on the influx of methionine into infected and uninfected erythrocytes of the L-system inhibitor aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH, 20 mM) (Christensen, 1979), and furosemide (200 lM), an effective inhibitor of the NPPs induced by the parasite in the plasma membrane of infected erythrocytes (Kirk et al, 1994). These measurements were made in the presence of protein synthesis inhibitors.…”

Section: Methionine Is Transported Into Intact Parasitised Erythrocytes Via the Endogenous L-system And The Nppsmentioning

confidence: 99%

Methionine transport in the malaria parasite Plasmodium falciparum

Cobbold

Martin

Kirk

2011

International Journal for Parasitology

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The intraerythrocytic malaria parasite, Plasmodium falciparum, derives amino acids from the digestion of host cell haemoglobin. However, it also takes up amino acids from the extracellular medium. Isoleucine is absent from adult human haemoglobin and an exogenous source of isoleucine is essential for parasite growth. An extracellular source of methionine is also important for the normal growth of at least some parasite strains. In this study we have characterised the uptake of methionine by P. falciparum-infected human erythrocytes, and by parasites functionally isolated from their host cells by saponin-permeabilization of the erythrocyte membrane. Infected erythrocytes take up methionine much faster than uninfected erythrocytes, with the increase attributable to the flux of this amino acid via the New Permeability Pathways induced by the parasite in the erythrocyte membrane. Having entered the infected cell, methionine is taken up by the intracellular parasite via a saturable, temperature-dependent process that is independent of ATP, Na(+) and H(+). Substrate competition studies, and comparison of the transport of methionine with that of isoleucine and leucine, yielded results consistent with the hypothesis that the parasite has at its surface one or more transporters which mediate the flux into and out of the parasite of a broad range of neutral amino acids. These transporters function most efficiently when exchanging one neutral amino acid for another, thus providing a mechanism whereby the parasite is able to import important exogenous amino acids in exchange for surplus neutral amino acids liberated from the digestion of host cell haemoglobin.

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Section: Methionine Is Transported Into Intact Parasitised Erythrocytes Via the Endogenous L-system And The Nppsmentioning

confidence: 99%

Methionine transport in the malaria parasite Plasmodium falciparum

Cobbold

Martin

Kirk

2011

International Journal for Parasitology

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“…As a result of pioneering work, in particular originating from Christensen et al a great variety of mammalian amino acid transport proteins have been identified, most of them are distributed within both the placental microvillous and the basolateral membranes. Historically, placental amino acid transport systems have been arranged based upon whether they were sodium-dependent or sodium-independent, and whether systems preferred cationic, zwitterionic or anionic substrates (141)(142)(143)(144). System A, Beta and Gly are associated with sodium-dependent accumulation of small neutral amino acids, beta amino acids (i.e.…”

Section: Amino Acid Metabolism and Transport In Pregnancymentioning

confidence: 99%

Maternal-fetal metabolism in normal pregnancy and preeclampsia

Versen-Hoeynck

Powers²

2007

Front Biosci

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Adaptation to pregnancy in humans involves major anatomic, physiologic and metabolic changes in the mother in order to support and provide for the nutritional and metabolic needs of the growing conceptus. Metabolically, pregnancy is marked by several important and dynamic adjustments including increased insulin resistance, hyperlipidemia and changes in protein and amino acid metabolism. In general, these metabolic adaptations serve to increase nutrient availability for the benefit of the growing fetal-placental unit. Interestingly, the pregnancy complication preeclampsia is recognized to evidence biologic exaggerations of these normal metabolic adaptations of pregnancy. Specifically, preeclampsia is associated with increased insulin resistance, hypertriglyceridemia, high circulating free fatty acids, low high-density lipoprotein particles, and high maternal and fetal plasma amino acid concentrations. These metabolic alterations may contribute to the pathophysiology of the syndrome and may also influence fetal growth. The focus of this review will be to summarize the normal metabolic adaptations, transport and utilization of carbohydrates, lipids and amino acids that occur during pregnancy. Furthermore, we will review the differences in carbohydrate, lipid and amino acid metabolism in pregnancies complicated by preeclampsia in comparison to uncomplicated pregnancies.

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“…Figure 1B illustrates the effects on the influx of isoleucine into infected and uninfected erythrocytes of aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH, 20 mM), an inhibitor of the L system, 28 and furosemide (200 M), an effective inhibitor of the new permeability pathways (NPPs) induced by the parasite in the plasma membrane of infected erythrocytes. 14 In uninfected erythrocytes, BCH reduced the influx of isoleucine by approximately 80%, consistent with the L system being the major route of entry for isoleucine and mediating a flux of 91 Ϯ 5 mol/(10 12 cells ⅐ hour) (n ϭ 4).…”

Section: Isoleucine Is Transported Into Intact Parasitized Erythrocytmentioning

confidence: 99%

Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum

Martin

Kirk

2006

Blood

108

116

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The intraerythrocytic malaria parasite derives much of its requirement for amino acids from the digestion of the hemoglobin of its host cell. However, one amino acid, isoleucine, is absent from adult human hemoglobin and must therefore be obtained from the extracellular medium. In this study we have characterized the mechanisms involved in the uptake of isoleucine by the intraerythrocytic parasite. Under physiologic conditions the rate of transport of isoleucine into human erythrocytes infected with mature trophozoite-stage Plasmodium falciparum parasites is increased to approximately 5-fold that in uninfected cells, with the increased flux being via the new permeability pathways (NPPs) induced by the parasite in the host cell membrane. Transport via the NPPs ensures that protein synthesis is not rate limited by the flux of isoleucine across the erythrocyte membrane. On entering the infected erythrocyte, isoleucine is taken up into the parasite via a saturable, ATP-, Na+-, and H+-independent system which has the capacity to mediate the influx of isoleucine in exchange for leucine (liberated from hemoglobin). The accumulation of radiolabeled isoleucine within the parasite is mediated by a second (high-affinity, ATP-dependent) mechanism, perhaps involving metabolism and/or the concentration of isoleucine within an intracellular organelle.

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Exploiting Amino acid Structure to Learn About Membrane Transport

Cited by 109 publications

References 185 publications

Methionine transport in the malaria parasite Plasmodium falciparum

Methionine transport in the malaria parasite Plasmodium falciparum

Maternal-fetal metabolism in normal pregnancy and preeclampsia

Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum

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