Ion Transport Through Cell Membrane: a Few Nonpolar
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Low Affinity Uniporter Carrier Proteins Can Increase Net Substrate Uptake
www.nature.com/scientificreports OPEN Low afnity uniporter carrier proteins can increase net substrate uptake rate by reducing efux Received: 10 November 2017 Evert Bosdriesz 1,3, Meike T. Wortel 1,4, Jurgen R. Haanstra 1, Marijke J. Wagner1, Accepted: 9 March 2018 Pilar de la Torre Cortés2 & Bas Teusink 1 Published: xx xx xxxx Many organisms have several similar transporters with diferent afnities for the same substrate. Typically, high-afnity transporters are expressed when substrate is scarce and low-afnity ones when it is abundant. The beneft of using low instead of high-afnity transporters remains unclear, especially when additional nutrient sensors are present. Here, we investigate two hypotheses. It was previously hypothesized that there is a trade-of between the afnity and the catalytic efciency of transporters, and we fnd some but no defnitive support for it. Additionally, we propose that for uptake by facilitated difusion, at saturating substrate concentrations, lowering the afnity enhances the net uptake rate by reducing substrate efux. As a consequence, there exists an optimal, external-substrate- concentration dependent transporter afnity. A computational model of Saccharomyces cerevisiae glycolysis shows that using the low afnity HXT3 transporter instead of the high afnity HXT6 enhances the steady-state fux by 36%. We tried to test this hypothesis with yeast strains expressing a single glucose transporter modifed to have either a high or a low afnity. However, due to the intimate link between glucose perception and metabolism, direct experimental proof for this hypothesis remained inconclusive. Still, our theoretical results provide a novel reason for the presence of low-afnity transport systems. -
Cellular Biology 1
Cellular biology 1 INTRODUCTION • Specialized intracellular membrane-bound organelles (Fig. 1.2), such as mitochondria, Golgi apparatus, endoplasmic reticulum (ER). This chapter is an overview of eukaryotic cells, addressing • Large size (relative to prokaryotic cells). their intracellular organelles and structural components. A basic appreciation of cellular structure and function is important for an understanding of the following chapters’ information concerning metabolism and nutrition. For fur- ther detailed information in this subject area, please refer to EUKARYOTIC ORGANELLES a reference textbook. Nucleus The eukaryotic cell The nucleus is surrounded by a double membrane (nuclear Humans are multicellular eukaryotic organisms. All eukary- envelope). The envelope has multiple pores to allow tran- otic organisms are composed of eukaryotic cells. Eukaryotic sit of material between the nucleus and the cytoplasm. The cells (Fig. 1.1) are defined by the following features: nucleus contains the cell’s genetic material, DNA, organized • A membrane-limited nucleus (the key feature into linear structures known as chromosomes. As well as differentiating eukaryotic cells from prokaryotic cells) chromosomes, irregular zones of densely staining material that contains the cell’s genetic material. are also present. These are the nucleoli, which are responsible Inner nuclear Nucleus membrane Nucleolus Inner Outer Outer mitochondrial nuclear mitochondrial membrane membrane membrane Ribosome Intermembrane space Chromatin Mitochondrial Rough matrix Mitochondrial Nuclear endoplasmic ribosome pore reticulum Crista Mitochondrial mRNA Smooth Vesicle endoplasmic Mitochondrion Circular reticulum mitochondrial Proteins of the DNA Vesicle budding electron transport off rough ER Vesicles fusing system with trans face of Cytoplasm Golgi apparatus ‘Cis’ face + discharging protein/lipid Golgi apparatus ‘Trans’ face Lysosome Vesicles leaving Golgi with modified protein/lipid cargo Cell membrane Fig. -
Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level
International Journal of Molecular Sciences Review Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level Sweilem B. Al Rihani 1 , Lucy I. Darakjian 1, Malavika Deodhar 1 , Pamela Dow 1 , Jacques Turgeon 1,2 and Veronique Michaud 1,2,* 1 Tabula Rasa HealthCare, Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; [email protected] (S.B.A.R.); [email protected] (L.I.D.); [email protected] (M.D.); [email protected] (P.D.); [email protected] (J.T.) 2 Faculty of Pharmacy, Université de Montréal, Montreal, QC H3C 3J7, Canada * Correspondence: [email protected]; Tel.: +1-856-938-8697 Abstract: The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies. -
Passive and Active Transport
Passive and Active Transport 1. Thermodynamics of transport 2. Passive-mediated transport 3. Active transport neuron, membrane potential, ion transport Membranes • Provide barrier function – Extracellular – Organelles • Barrier can be overcome by „transport proteins“ – To mediate transmembrane movements of ions, Na+, K+ – Nutrients, glucose, amino acids etc. – Water (aquaporins) 1) Thermodynamics of Transport • Aout <-> Ain (ressembles a chemical equilibration) o‘ • GA - G A = RT ln [A] • ∆GA = GA(in) - GA(out) = RT ln ([A]in/[A]out) • GA: chemical potential of A o‘ • G A: chemical potential of standard state of A • If membrane has a potential, i.e., plasma membrane: -100mV (inside negative) then GA is termed the electrochemical potential of A Two types of transport across a membrane: o Nonmediated transport occurs by passive diffusion, i.e., O2, CO2 driven by chemical potential gradient, i.e. cannot occur against a concentration gradient o Mediated transport occurs by dedicated transport proteins 1. Passive-mediated transport/facilitated diffusion: [high] -> [low] 2. Active transport: [low] -> [high] May require energy in form of ATP or in form of a membrane potential 2) Passive-mediated transport Substances that are too large or too polar to diffuse across the bilayer must be transported by proteins: carriers, permeases, channels and transporters A) Ionophores B) Porins C) Ion Channels D) Aquaporins E) Transport Proteins A) Ionophores Organic molecules of divers types, often of bacterial origin => Increase the permeability of a target membrane for ions, frequently antibiotic, result in collapse of target membrane potential by ion equilibration 1. Carrier Ionophore, make ion soluble in membrane, i.e. valinomycin, 104 K+/sec 2. -
Evidence for a Respiratory Chain in the Chloroplast
Proc. NatL Acad. Sci. USA Vol. 79, pp. 4352-4356, July 1982 Cell Biology Evidence for a respiratory chain in the chloroplast (photosynthesis/respiration/starch degradation/evolution) PIERRE BENNOUN Institut de Biologie Physico-Chimique, 13, rue Pierre et Marie Curie, 75005, Paris, France Communicated by Pierre Joliot, April 12, 1982 ABSTRACT Evidence is given for the existence ofan electron in 20 ml of 20 mM N-tris(hydroxymethyl)methylglycine(Tri- transport pathway to oxygen in the thylakoid membranes ofchlo- cine)/KOH, pH 7.8/10 mM NaCl/10 mM MgCl2/1 mM K2- roplasts (chlororespiration). Plastoquinone is shown to be a redox HPO4/0.1 M sucrose/5% Ficoll. The cell suspension was carrier common to both photosynthetic and chlororespiratory passed through a Yeda press operated at 90 kg/cm2, diluted pathways. It is shown that, in dark-adapted chloroplasts, an elec- with 200 ml of Ficoll-lacking buffer, and centrifuged, and the trochemical gradient is built up across the thylakoid membrane pellet was suspended in the same buffer. by transfer of electrons through the chlororespiratory chain as Chlorophyll fluorescence kinetics and luminescence mea- well as by reverse functioning of the chloroplast ATPases. It is surements were performed as described (9). proposed that these mechanisms ensure recycling ofthe ATP and NAD(P)H generated by the glycolytic pathway converting starch into triose phosphates. Chlororespiration is thus an 02-uptake RESULTS process distinct from photorespiration and the Mehler reaction. The plastoquinone (PQ) pool ofchloroplast is a redox carrier of The evolutionary significance of chlororespiration is discussed. the photosynthetic electron transport chain. -
The Electrochemical Gradient of Protons and Its Relationship to Active Transport in Escherichia Coli Membrane Vesicles
Proc. Natl. Acad. Sci. USA Vol. 73, No. 6, pp. 1892-1896, June 1976 Biochemistry The electrochemical gradient of protons and its relationship to active transport in Escherichia coli membrane vesicles (flow dialysis/membrane potential/energy transduction/lipophilic cations/weak acids) SOFIA RAMOS, SHIMON SCHULDINER*, AND H. RONALD KABACK The Roche Institute of Molecular Biology, Nutley, New Jersey 07110 Communicated by B. L. Horecker, March 17, 1976 ABSTRACT Membrane vesicles isolated from E. coli gen- presence of valinomycin), a respiration-dependent membrane erate a trans-membrane proton gradient of 2 pH units under potential (AI, interior negative) of approximately -75 mV in appropriate conditions when assayed by flow dialysis. Using E. coli membrane vesicles has been documented (6, 13, 14). the distribution of weak acids to measure the proton gradient (ApH) and the distribution of the lipophilic cation triphenyl- Moreover it has been shown that the potential causes the ap- methylphosphonium to measure the electrical potential across pearance of high affinity binding sites for dansyl- and azido- the membrane (AI), the vesicles are shown to generate an phenylgalactosides on the outer surface of the membrane (4, electrochemical proton gradient (AiH+) of approximately -180 15) and that the potential is partially dissipated as a result of mV at pH 5.5 in the presence of ascorbate and phenazine lactose accumulation (6). Although these findings provide ev- methosulfate, the major component of which is a ApH of about idence for the chemiosmotic hypothesis, it has also been dem- -110 mV. As external pH is increased, ApH decreases, reaching o at pH 7.5 and above, while AI remains at about -75 mV and onstrated (6, 16) that vesicles are able to accumulate lactose and internal pH remains at pH 7.5. -
Arxiv:1912.06275V2 [Q-Bio.BM] 18 Feb 2021
General Principles of Secondary Active Transporter Function Oliver Beckstein1, a) and Fiona Naughton1 Department of Physics, Arizona State University, Tempe AZ 85287, USA (Dated: February 19, 2021) Transport of ions and small molecules across the cell membrane against electrochemical gradients is catalyzed by integral membrane proteins that use a source of free energy to drive the energetically uphill flux of the transported substrate. Secondary active transporters couple the spontaneous influx of a “driving” ion such as Na+ or H+ to the flux of the substrate. The thermodynamics of such cyclical non-equilibrium systems are well understood and recent work has focused on the molecular mechanism of secondary active transport. The fact that these transporters change their conformation between an inward-facing and outward-facing conformation in a cyclical fashion, called the alternating access model, is broadly recognized as the molecular framework in which to describe transporter function. However, only with the advent of high resolution crystal structures and detailed computer simulations has it become possible to recognize common molecular-level principles between disparate transporter families. Inverted repeat symmetry in secondary active transporters has shed light on how protein structures can encode a bi-stable two-state system. More detailed analysis (based on experimental structural data and detailed molecular dynamics simulations) indicates that transporters can be understood as gated pores with at least two coupled gates. These gates are not just a convenient cartoon element to illustrate a putative mechanism but map to distinct parts of the transporter protein. Enumerating all distinct gate states naturally includes occluded states in the alternating access picture and also suggests what kind of protein conformations might be observable. -
Membrane Transport Quiz
Membrane Transport Quiz 1. Which of the following is an example of extracellular fluid? a. Cytosol b. Plasma c. Interstitial Fluid d. Both b and c 2. Which of the following correctly describes passive transport? a. the cell uses ATP in passive transport b. most pumps are examples of passive transport c. diffusion is an example of passive transport d. exocytosis is an example of passive transport 3. Simple diffusion occurs ______________. a. with transporters in the cell membrane b. directly across the cell membrane c. through exocytosis d. through endocytosis 4. Which of the following is an example of active transport? a. Filtration b. Osmosis c. Endocytosis d. Exocytosis e. Both c and d 5. Which type of active transport uses ATP directly? a. Primary Active Transport b. Secondary Active Transport c. Both a and b 6. Which of the following is an example of receptor mediated endocytosis? a. Phagocytosis b. Primary Active Transport c. Exocytosis d. ALL are For use with TCC iTunes University Membrane Transport Lecture. 1 Developed by: Martha Kutter 2009 for the Learning Commons at Tallahassee Community College. 7. A transporter that moves one type of particle in one direction is _______________. a. Uniporter b. Symporter c. Antiporter 8. A transporter the moves two different particles in two different directions is ________. a. Endocytosis b. Exocytosis c. Uniporter d. Symporter e. Antiporter 9. Which of the following is an example of a primary active transporter? a. Na+/Ca2+ transporter on cardiac contractile cells b. Na+ channels on neurons c. Na+/K+ ATPase on all cells d. -
Photosynthesis and Respiration
18 Photosynthesis and Respiration ATP is the energy currency of the cell Goal To understand how energy from sunlight is harnessed to Cells need to carry out many reactions that are energetically unfavorable. generate chemical energy by photosynthesis and You have seen some examples of these non-spontaneous reactions in respiration. earlier chapters: the synthesis of nucleic acids and proteins from their corresponding nucleotide and amino acid building blocks and the transport Objectives of certain ions against concentration gradients across a membrane. In many cases, unfavorable reactions like these are coupled to the hydrolysis of ATP After this chapter, you should be able to: in order to make them energetically favorable under cellular conditions; we • Explain the concepts of oxidation and have learned that for these reactions the free energy released in breaking reduction. the phosphodiester bonds in ATP exceeds the energy consumed by the • Explain how light energy generates an uphill reaction such that the sum of the free energy of the two reactions is electrochemical gradient. negative (ΔG < 0). To perform these reactions, cells must then have a way • Explain how an electrochemical of generating ATP efficiently so that a sufficient supply is always available. gradient generates chemical energy. The amount of ATP used by a mammalian cell has been estimated to be on the order of 109 molecules per second. In other words, ATP is the principal • Explain how chemical energy is harnessed to fix carbon dioxide. energy currency of the cell. • Explain how glucose is used to generate How does the cell produce enough ATP to sustain life and what is the source ATP anaerobically. -
3. Transport Can Be Active Or Passive. •Passive Transport Is Movement
3. Transport can be active or passive. F 6-3 Taiz. Microelectrodes are used to measure membrane •Passive transport is movement down an electrochemical potentials across cell membrane gradient. •Active transport is movement against an electrochemical gradient. What is an electrochemical gradient? How is it formed? Passive and active transport of ions result in electric potential difference across membranes. •Movement of an uncharged mol Is dependent on conc. gradient alone. •Movement of an ion depends on the electric gradient and the conc. gradient. •Diffusion potential- Pump potential- How do you know if an ion is moving uphill or downhill? Nernst Eq What is the driving force for uphill movement? A) ATP ; b) H+ gradient 6-5. Pump potential and diffusion potential. How can we determine whether an ion moves in or out by active or passive transport? Nernst equation states that at equilibrium the difference in concentration of an ion between two compartments is balanced by the voltage difference. Thus it can predict the ion conc at equilibrium at a certain ΔE. Very useful to predict active or passive transport of an ion. Fig. 6-4, Taiz. Passive and active transporters. Tab 6-1, Taiz . Using the Nernst equation to predict ion conc. at equilibrium when the Cell electrical potential, Δψ = -110 mV ---------------------------------------------------------------------------------------- Ext Conc. Ion Internal concentration (mM) Summary: In general observed Nernst (Predicted) ---------------------------------------------------------------------------------------- Cation uptake: passive 1 mM K+ 75 mM 74 Cation efflux: active 1 mM Na+ 8 mM 74 1 mM Ca2+ 2 mM 5,000 Anion uptake: active 0.2 mM Mg2+ 3 1,340 Anion release: passive - 2 mM NO3 5 mM 0.02 1 Cl- 10 mM 0.01 - 1H2PO4 21 0.01 ---------------------------------------------------------------------------------------- 1 6-10. -
Molecular Biology of the Cell 6Th Edition
753 CHAPTER Energy Conversion: Mitochondria and Chloroplasts 14 To maintain their high degree of organization in a universe that is constantly drift- IN THIS CHAPTER ing toward chaos, cells have a constant need for a plentiful supply of ATP, as we have explained in Chapter 2. In eukaryotic cells, most of the ATP that powers life THE MITOCHONDRION processes is produced by specialized, membrane-enclosed, energy-converting organelles. Tese are of two types. Mitochondria, which occur in virtually all cells THE PROTON PUMPS OF THE of animals, plants, and fungi, burn food molecules to produce ATP by oxidative ELECTRON-TRANSPORT CHAIN phosphorylation. Chloroplasts, which occur only in plants and green algae, har- ness solar energy to produce ATP by photosynthesis. In electron micrographs, the ATP PRODUCTION IN most striking features of both mitochondria and chloroplasts are their extensive MITOCHONDRIA internal membrane systems. Tese internal membranes contain sets of mem- brane protein complexes that work together to produce most of the cell’s ATP. In CHLOROPLASTS AND bacteria, simpler versions of essentially the same protein complexes produce ATP, PHOTOSYNTHESIS but they are located in the cell’s plasma membrane (Figure 14–1). Comparisons of DNA sequences indicate that the energy-converting organ- THE GENETIC SYSTEMS elles in present-day eukaryotes originated from prokaryotic cells that were endo- OF MITOCHONDRIA AND cytosed during the evolution of eukaryotes (discussed in Chapter 1). This explains CHLOROPLASTS why mitochondria and chloroplasts contain their own DNA, which still encodes a subset of their proteins. Over time, these organelles have lost most of their own genomes and become heavily dependent on proteins that are encoded by genes in the nucleus, synthesized in the cytosol, and then imported into the organelle. -
Amino Acids, Peptides, and Proteins
1/11/2018 King Saud University College of Science Department of Biochemistry Biomembranes and Cell Signaling (BCH 452) Chapter 3 Diffusion, Channels and Transport Systems Prepared by Dr. Farid Ataya http://fac.ksu.edu.sa/fataya Lect Topics to be covered No. Role of cell surface carbohydrates in recognise ion, as receptor of antigens, 7 hormones, toxins, viruses and bacteria. Their role in histocompatibility and cell-cell adhesion. Diffusion. 8 Diffusion across biomembranes. Ficks law. Structural types of channels (pores): -type, -barrel, pore forming toxins, ionophores. Functional types of channels (pores): voltage-gated channels e.g. sodium channels, ligand-gated channels e.g. acetylcholine receptor (nicotinic-acetylcholine channel), c-AMP regulated. Gap junctions and nuclear pores. 9 Transport systems: Energetics of transport systems, G calculation in each type. Passive Transport (facilitated diffusion). 1 1/11/2018 No. Topics to be covered Lect Kinetic properties. 9 Passive transport: Glucose transporters (GLUT 1 to5), - C1 , HCO3 exchanger (anion exchanger protein) in erythrocyte membrane Kinetic properties. 10 Active transport: Types of active transport: Primary ATPases (Primary active transporters): P transporters (e.g. Na+, K+, ATPase) First assessment Exam ATP binding cassettes (ABC transports) 11 (e.g. cystic fibrosis transmembrane conductance regulator-chloride transport). Multidrug resistance protein transporter. V transporters, F transporters. Secondary active transporters (e.g. Na+ -dependent transport of glucose and amino acids). To be covered under intestinal brush border Transport of large molecules (Macromolecules) 12 Types: Exocytosis, Endocytosis-pinocytosis and phagocytosis Types of pinocytosis: Absorptive pinocytosis, characteristics and examples. Fluid phase pinocytosis, characteristics and examples The role of cell surface carbohydrates: Glycoproteins Membrane glycoproteins are proteins that contain 1-30% carbohydrate in their structure.