NPPs 2001 Kirk
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Questions and Answers

What is primarily altered in the parasitized erythrocyte after malaria infection?

  • Endogenous transport properties (correct)
  • Oxygen consumption
  • Cell size
  • Membrane fluidity

    • What role do new permeation pathways (NPP) play in the context of malaria infection?

  • Alteration of endogenous transport systems (correct)
  • Regulation of cellular apoptosis
  • Facilitation of nutrient absorption
  • Implantation of red blood cells

    • Which malaria parasite is the main focus of the review discussing membrane transport systems?

  • P.knowlesi
  • P.malariae
  • P.falciparum (correct)
  • P.vivax

    • What is critical for the survival of the malaria parasite within the host cell?

    <p>Elimination of waste products (D)</p> Signup and view all the answers

    In what year did the in vitro culture system for P.falciparum become available?

    <p>1976 (C)</p> Signup and view all the answers

    What is a key focus regarding membrane transport in infected erythrocytes?

    <p>Regulation of ion transport (C)</p> Signup and view all the answers

    What is the primary focus of Section II in the review?

    <p>Intraerythrocytic phase of the parasite life cycle (B)</p> Signup and view all the answers

    What is one of the challenges mentioned regarding methodologies used in the study of membrane transport?

    <p>Advantages and shortcomings of techniques (A)</p> Signup and view all the answers

    What is the primary reason the malaria parasite invades red blood cells?

    <p>To evade the host's immune system (B)</p> Signup and view all the answers

    Which type of ion is found in high concentrations within the intracellular environment of the host erythrocyte?

    <p>K⁺ (B)</p> Signup and view all the answers

    What kind of transporter has been identified on chromosome 2 of P. falciparum?

    <p>Hexose sugar transporter (C)</p> Signup and view all the answers

    How many chromosomes does P. falciparum have?

    <p>14 (C)</p> Signup and view all the answers

    What is the primary challenge faced by the malaria parasite inside the erythrocyte?

    <p>Unusual extracellular environment (A)</p> Signup and view all the answers

    Which component of the host's red blood cells does the malaria parasite primarily utilize for its survival?

    <p>Hemoglobin (C)</p> Signup and view all the answers

    Which ion's level is notably low within the erythrocyte, posing a challenge for the malaria parasite?

    <p>Na⁺ (D)</p> Signup and view all the answers

    What has been established about the sequences of transporters encoded by Plasmodium?

    <p>Only two sequences have identified functions. (B)</p> Signup and view all the answers

    What is the main energy source for the malaria parasite as it matures in the infected erythrocyte?

    <p>Glycolysis (A)</p> Signup and view all the answers

    At what stage does the malaria parasite start to increase its metabolic and biosynthetic activity after invading the erythrocyte?

    <p>15 hours post-invasion (C)</p> Signup and view all the answers

    How much does the rate of glucose utilization in the parasitized cell increase compared to the uninfected erythrocyte?

    <p>100 times (D)</p> Signup and view all the answers

    What cellular structure does the malaria parasite utilize to digest the host's hemoglobin?

    <p>Cyto stomal vesicles (D)</p> Signup and view all the answers

    During which phase of the malaria parasite life cycle does the organism initially seem dormant?

    <p>Ring stage (B)</p> Signup and view all the answers

    Which transport mechanism is critical for nutrient acquisition in malaria-infected erythrocytes?

    <p>Endocytosis (D)</p> Signup and view all the answers

    What notable feature is absent in the malaria parasite's mitochondrion?

    <p>Citric acid cycle (A)</p> Signup and view all the answers

    What is the primary function of the food vacuole in malaria-infected erythrocytes?

    <p>Digest hemoglobin (A)</p> Signup and view all the answers

    Flashcards

    Malaria parasite life cycle

    The malaria parasite invades red blood cells, causing malaria symptoms.

    Host erythrocyte environment

    High K+, proteins, low Na+, and trace Ca2+ inside red blood cells.

    Parasite survival strategy

    Living inside host cells allows evasion of the host's immune system.

    Membrane transporters in Malaria

    Genes encoding proteins that transport substances, crucial for the parasite's nutrient uptake and waste removal.

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    Plasmodium-encoded transporters

    Proteins found only in Plasmodium, responsible for transporting specific molecules.

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    Malaria clinical symptoms

    Symptoms arise from the parasite's presence inside red blood cells during its life cycle.

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    Protein Sequence Analysis

    Studying the order of amino acids in proteins can reveal related functions and evolutionary relationships.

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    Malaria Genetic Techniques

    Applying genetic techniques (analysis of genome sequencing) has shed new light on malaria parasite behavior, function and life cycle.

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    Intraerythrocytic malaria parasite

    The malaria parasite that lives inside red blood cells (erythrocytes).

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    Membrane transport systems

    Mechanisms that control the movement of substances across cell membranes.

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    P. falciparum

    A virulent malaria parasite infecting humans; the major focus of the review.

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    Host cell cytosol

    The fluid inside the host cell where resources are located.

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    Nutrient acquisition

    The process of obtaining necessary substances from the host cell.

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    Metabolic waste elimination

    The removal of waste products from the parasite and host cell.

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    New permeation pathways (NPP)

    Specialized pathways in infected cells for transport that the parasite developed.

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    Parasite life cycle

    The stages the parasite goes through inside the host.

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    Malaria parasite life cycle

    The stages of a malaria parasite's development inside a red blood cell (erythrocyte).

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    Intraerythrocytic phase

    The stage of the malaria parasite's life cycle occurring inside the red blood cell.

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    Membrane transport

    The process by which substances move across cell membranes. This is important for the malaria parasite to function.

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    Compartmentalization

    The partitioning of the malaria-infected red blood cell's interior into different regions with distinct functions.

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    Glucose utilization

    The process of the malaria parasite using glucose for energy.

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    Metabolic activity

    The chemical processes occurring within the malaria-parasitized cell.

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    Transport properties

    Specific characteristics of movement across membranes in the malaria infected cell.

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    Solute Transport

    Movement of dissolved substances (solutes) through the cell membrane, specifically within infected red blood cells.

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    Study Notes

    Membrane Transport in Malaria-Infected Erythrocytes

    • Malaria parasites invade red blood cells (RBCs) during their life cycle
    • The parasite modifies RBC membrane permeability and cytosolic composition
    • The intracellular parasite is enclosed in a parasitophorous vacuolar membrane (PVM)
    • Tubular extensions of the PVM radiate into the host cell
    • The parasite also has a plasma membrane (PPM)
    • The parasite undergoes marked alteration in its membrane transport properties after infection

    Malaria Parasite Life Cycle

    • Parasites enter the vertebrate host through the bite of an infected mosquito
    • They invade liver cells, multiply, and release merozoites
    • Merozoites then invade RBCs
    • The parasite replicates within the RBCs, and then the infected RBCs burst releasing the merozoites to infect other RBCs

    Methods for Studying Membrane Transport

    • Cell Preparations: Obtaining synchronized suspensions of infected RBCs
      • Techniques for separating infected RBCs from uninfected
      • Methods for synchronizing parasites in culture
    • Radioisotope Fluxes: Measure solute influx and efflux using radiolabeled solutes
      • Measure initial rate of solute uptake
    • Isosmotic Hemolysis: Solute permeability is evaluated using isosmotic solutions
      • Compare solute permeation in infected and uninfected RBCs
    • Fluorescence: Use fluorescent solutes to track solute movement in real time.
      • Fluorescently labeled substrates are commonly used
      • Monitor intracellular compartmentalization and assess membrane transport properties.

    Solute Trafficking Routes

    • Solutes can enter the parasite through the sequential route (across RBC membrane, PVM, and ppm) or parallel routes (that do not enter the host cell cytosol)
    • Parallel routes include hypothetical metabolic windows or parasitophorous ducts
    • These parallel routes remain a contentious issue; evidence is indirect

    Red Blood Cell Membrane

    • The mature human RBC membrane has multiple transport systems
    • These systems regulate solute amounts and electrochemical gradients
    • Many pathways contribute to solute movement (e.g., Na+/K+ pump, NaKCl cotransporter)

    Parasitophorous Vacuolar Membrane (PVM)

    • The PVM forms during the invasion stage of the RBCs
    • Its composition is not entirely known
    • Emerging evidence indicates that proteins like glycophos-phatidylinositol-anchored (GPI) proteins are present
    • The PVM has a high permeability to small solutes

    Intracellular Organellar Membranes

    • The malaria parasite has a diverse range of intracellular organelles
    • Their transport properties are predominantly unknown

    Transport of Specific Solutes

    • Sugars: High rate of glucose uptake by infected RBCs; glucose transport is rapid in normal RBCs; other sugars are taken up via NPP.
    • Amino acids: The parasite has limited amino acid synthesis and requires external sources.
      • Specific transporter systems exist in normal RBCs
      • Uptake via NPP of most amino acids
    • Peptides: Di- and tripeptides cross the parasite-induced pathways and their uptake is enhanced.
    • Nucleosides: Parasites are capable of synthesizing pyrimidines; use of NPP for purine and pyrimidine nucleoside transport; The transport shows a broad specificity
    • Vitamins: Necessary for the parasite; examples and ways of uptake.
    • Choline: The rate of choline transport into parasitized RBCs from normal RBCs is higher
    • Lactate: The parasite's demand for lactate production is greater than the transport capacity of normal RBCs; evidence suggests transport across NPP.
    • ATP/ADP: A transporter in the parasite and host cell cytosol ensures similar ATP concentrations; this is affected by atractyloside.
    • Chloride (Cl¯): NPP are more permeable to Cl¯ than other ions; it affects the uptake/distribution of other substances.
    • Sodium, Potassium, and Protons (Na+, K+, H+): Normal RBCs maintain a [Na+]/[K+] gradient; this regulation is disturbed during the parasite's presence.
    • Calcium (Ca²⁺): Cellular Ca²⁺ plays a significant role, with malaria parasite Ca²⁺ localized inside the parasite at elevated levels; it remains unclear how Ca²⁺ homeostasis is maintained.
    • Magnesium (Mg²⁺): Intracellular Mg²⁺ levels are maintained by the parasite, even with changing external concentrations; this contrasts with its behaviour in normal RBCs.
    • Drugs: Chloroquine; resistance to chloroquine is linked to decreased vacuolar chloroquine accumulation

    Inhibitors of the NPP

    • Several compounds block the transport across the NPP

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