Concentration Gradient; Within a System, Different Substances in the Medium Will Each Diffuse at Different Rates According to Their Individual Gradients
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Osmosis, Diffusion, and Membrane Transport Bio 219 Napa Valley College Dr
Osmosis, Diffusion, and Membrane Transport Bio 219 Napa Valley College Dr. Adam Ross Overview In order to understand how cells regulate themselves, we must first understand how things move into and out of cells Diffusion • Diffusion is the movement of particles from an area of high charge or concentration to an area of lower charge or concentration • Referred to as moving “down” a charge or concentration gradient • Ex. H+ ions in mitochondria moving through ATP synthase • Result of random molecular motion • Fick’s Law of Diffusion gives rate of diffusion: • Rate = P A (Cout – Cin) / (x) • Rate is proportional to permeability (P), surface area (A), concentration gradient (Cout – Cin); inversely proportional to diffusion distance or membrane thickness (x) Gradients • Concentration • Caused by unequal distribution of a substance on either side of the membrane • If the inside of a cell is negative, it will attract positively charged things • Electrical (charge) • Caused by unequal distribution of charge on either side of the membrane Diffusion Osmosis • Osmosis is the movement of solvent through a semi permeable membrane in order to balance the solute concentration on either side of the membrane. • In cells the solvent is water • Water can cross membranes Osmosis Osmolarity • Total concentration of all solutes in a solution • 1 Osm = 1 mole solute/ L • Have to account for both atoms in salts • 1M NaCl +1 L H2O → 1M Na+ + 1M Cl ≈ 2 Osm • Plasma = 290 mOsm Osmotic pressure • This is the actual driving force for net water movement • Depends on -
Membrane Transport, Absorption and Distribution of Drugs
Chapter 2 1 Pharmacokinetics: Membrane Transport, Absorption and Distribution of Drugs Pharmacokinetics is the quantitative study of drug movement in, through and out of the body. The overall scheme of pharmacokinetic processes is depicted in Fig. 2.1. The intensity of response is related to concentration of the drug at the site of action, which in turn is dependent on its pharmacokinetic properties. Pharmacokinetic considerations, therefore, determine the route(s) of administration, dose, and latency of onset, time of peak action, duration of action and frequency of administration of a drug. Fig. 2.1: Schematic depiction of pharmacokinetic processes All pharmacokinetic processes involve transport of the drug across biological membranes. Biological membrane This is a bilayer (about 100 Å thick) of phospholipid and cholesterol molecules, the polar groups (glyceryl phosphate attached to ethanolamine/choline or hydroxyl group of cholesterol) of these are oriented at the two surfaces and the nonpolar hydrocarbon chains are embedded in the matrix to form a continuous sheet. This imparts high electrical resistance and relative impermeability to the membrane. Extrinsic and intrinsic protein molecules are adsorbed on the lipid bilayer (Fig. 2.2). Glyco- proteins or glycolipids are formed on the surface by attachment to polymeric sugars, 2 aminosugars or sialic acids. The specific lipid and protein composition of different membranes differs according to the cell or the organelle type. The proteins are able to freely float through the membrane: associate and organize or vice versa. Some of the intrinsic ones, which extend through the full thickness of the membrane, surround fine aqueous pores. CHAPTER2 Fig. -
Cellular Transport Notes About Cell Membranes
Cellular Transport Notes @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey About Cell Membranes • All cells have a cell membrane • Functions: – Controls what enters and exits the cell to maintain an internal balance called homeostasis TEM picture of a – Provides protection and real cell membrane. support for the cell @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 1 About Cell Membranes (continued) 1.Structure of cell membrane Lipid Bilayer -2 layers of phospholipids • Phosphate head is polar (water loving) Phospholipid • Fatty acid tails non-polar (water fearing) • Proteins embedded in membrane Lipid Bilayer @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey Polar heads Fluid Mosaic love water Model of the & dissolve. cell membrane Non-polar tails hide from water. Carbohydrate cell markers Proteins @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 2 About Cell Membranes (continued) • 4. Cell membranes have pores (holes) in it • Selectively permeable: Allows some molecules in and keeps other molecules out • The structure helps it be selective! Pores @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey Structure of the Cell Membrane Outside of cell Carbohydrate Proteins chains Lipid Bilayer Transport Protein Phospholipids Inside of cell (cytoplasm) @ 2011 Center for Pre-College Programs, New Jersey Institute of Technology, Newark, New Jersey 3 Types of Cellular Transport • Passive Transport celldoesn’tuseenergy 1. Diffusion 2. Facilitated Diffusion 3. Osmosis • Active Transport cell does use energy 1. -
CO2 Permeability of Biological Membranes and Role of CO2 Channels
membranes Review CO2 Permeability of Biological Membranes and Role of CO2 Channels Volker Endeward, Mariela Arias-Hidalgo, Samer Al-Samir and Gerolf Gros * Molekular-und Zellphysiologie, AG Vegetative Physiologie–4220–Medizinische Hochschule Hannover, 30625 Hannover, Germany; [email protected] (V.E.); [email protected] (M.A.-H.); [email protected] (S.A.-S.) * Correspondence: [email protected]; Fax: +49-511-5322938 Received: 17 September 2017; Accepted: 18 October 2017; Published: 24 October 2017 Abstract: We summarize here, mainly for mammalian systems, the present knowledge of (a) the membrane CO2 permeabilities in various tissues; (b) the physiological significance of the value of the CO2 permeability; (c) the mechanisms by which membrane CO2 permeability is modulated; (d) the role of the intracellular diffusivity of CO2 for the quantitative significance of cell membrane CO2 permeability; (e) the available evidence for the existence of CO2 channels in mammalian and artificial systems, with a brief view on CO2 channels in fishes and plants; and, (f) the possible significance of CO2 channels in mammalian systems. Keywords: CO2 permeability; membrane cholesterol; protein CO2 channels; aquaporins; Rhesus proteins; aquaporin-1-deficient mice 1. Introduction This review intends to update the state of this field as it has been given by Endeward et al. [1] in 2014. In addition, we attempt to give a compilation of all of the lines of evidence that have so far been published demonstrating the existence of protein CO2 channels and their contributions to membrane CO2 permeability. We also give a compilation of the recently described remarkable variability of the CO2 permeability in mammalian cell membranes. -
Palmitoylation: Implications for Nitric Oxide Signaling
Proc. Natl. Acad. Sci. USA Vol. 93, pp. 6448-6453, June 1996 Cell Biology Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: Implications for nitric oxide signaling (endothelial nitric oxide synthase/signal transduction/vascular biology/N-myristoylation) GUILLERMO GARC1A-CARDENA*, PHIL OHt, JIANwEI LIu*, JAN E. SCHNITZERt, AND WILLIAM C. SESSA*t *Molecular Cardiobiology Program and Department of Pharmacology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536; and tDepartment of Pathology, Harvard Medical School, Beth Israel Hospital, 330 Brookline Avenue, Boston, MA 02215 Communicated by Vincent T. Marchesi, Yale Univeristy, New Haven, CT, March 13, 1996 (received for review February 5, 1996) ABSTRACT The membrane association of endothelial insoluble membranes (TIM), suggesting that caveolae are nitric oxide synthase (eNOS) plays an important role in the signal processing centers (2-11). Additionally, caveolae have biosynthesis of nitric oxide (NO) in vascular endothelium. been implicated in other important cellular functions, includ- Previously, we have shown that in cultured endothelial cells ing endocytosis, potocytosis, and transcytosis (12, 13). and in intact blood vessels, eNOS is found primarily in the Endothelial nitric oxide synthase (eNOS) is a peripheral perinuclear region of the cells and in discrete regions of the membrane protein that metabolizes L-arginine to nitric oxide plasma membrane, suggesting trafficking of the protein from (NO). NO is a short-lived free radical gas involved in diverse the Golgi to specialized plasma membrane structures. Here, physiological and pathological processes. Endothelial-derived we show that eNOS is found in Triton X-100-insoluble mem- NO is an important paracrine mediator of vascular smooth branes prepared from cultured bovine aortic endothelial cells muscle tone and is an inhibitor of leukocyte adhesion and and colocalizes with caveolin, a coat protein of caveolae, in platelet aggregation (14, 15). -
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. -
Identification of Caveolin and Caveolin-Related Proteins in the Brain
The Journal of Neuroscience, December 15, 1997, 17(24):9520–9535 Identification of Caveolin and Caveolin-Related Proteins in the Brain Patricia L. Cameron, Johnna W. Ruffin, Roni Bollag, Howard Rasmussen, and Richard S. Cameron Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912-3175 Caveolae are 50–100 nm, nonclathrin-coated, flask-shaped brane. Immunoblot analyses demonstrate that detergent- plasma membrane microdomains that have been identified in insoluble complexes isolated from astrocytes are composed of most mammalian cell types, except lymphocytes and neurons. caveolin-1a, an identification verified by Northern blot analyses To date, multiple functions have been ascribed to caveolae, and by the cloning of a cDNA using reverse transcriptase-PCR including the compartmentalization of lipid and protein compo- amplification from total astrocyte RNA. Using a full-length nents that function in transmembrane signaling events, biosyn- caveolin-1 probe, Northern blot analyses suggest that the ex- thetic transport functions, endocytosis, potocytosis, and trans- pression of caveolin-1 may be regulated during brain develop- cytosis. Caveolin, a 21–24 kDa integral membrane protein, is ment. Immunoblot analyses of detergent-insoluble complexes the principal structural component of caveolae. We have initi- isolated from cerebral cortex and cerebellum identify two im- ated studies to examine the relationship of detergent-insoluble munoreactive polypeptides with apparent molecular weight and complexes identified -
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. -
Folate Receptors Targeted to Clathrin-Coated Pits Cannot Regulate Vitamin Uptake
Proc. Natl. Acad. Sci. USA Vol. 92, pp. 3824-3828, April 1995 Cell Biology Folate receptors targeted to clathrin-coated pits cannot regulate vitamin uptake (caveolae/glycosyl-phosphatidylinositol/potocytosis/endocytosis/5-methyltetrahydrofolate) TIMOTHY E. RITTER*, OSVALDo FAJARDO*, HIROYUKI MATSUEt, RICHARD G. W. ANDERSONt, AND STEPHEN W. LACEY*§ Departments of *Internal Medicine, tDermatology and Cell Biology, and tNeuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75235 Communicated by Michael S. Brown, University of Texas Southwestern Medical Center, Dallas, TX, January 3, 1995 ABSTRACT Potocytosis is an endocytic process that is coated pits (6). Clearly it is not the initial internalization step specialized for the internalization of small molecules. Recent that is advantageous, because the rate of ligand sequestration studies on the uptake of5-methyltetrahydrofolate by the folate by caveolae is about 5 times slower (17) than that by clathrin- receptor have suggested that the glycosyl-phosphatidylinositol coated pits (18). Nothing is known, however, about how the anchor on this protein causes it to cluster and be internalized two pathways might differ in either the efficiency of ligand by caveolae instead of coated pits. To test this hypothesis delivery to the cytoplasm or the regulation of folate accumu- directly, we have constructed a chimeric folate receptor that lation in the cytoplasm. We have addressed these two questions has the glycosyl-phosphatidylinositol anchor replaced with by constructing a chimeric folate receptor that is internalized the transmembrane domain and cytoplasmic tail of the low by clathrin-coated pits and the comparing uptake of 5-MeTHF density lipoprotein receptor. The cells with wild-type recep- by this receptor with uptake by the wild-type receptor in tors delivered 5-methyltetrahydrofolate to the cytoplasm more transfected cells. -
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. -
Cell Transport
Cells and their Environment Transport occurs across the cell membrane and helps a cell to maintain homeostasis. Cell part responsible: 5/16/14 1 1. Movement of materials across the membrane is called transport. A. Passive Transport - WITHOUT the use of energy • Driven by Kinetic energy/Brownian motion B. Active Transport - WITH the use of energy- against a concentration gradient 5/16/14 2 2. Concentration Gradient- difference in concentration from one area to another Visual Concept 5/16/14 3 3. Diffusion is passive/no energy. a) Diffusion- high to low concentration. b) Quicker at higher temps c) Occurs until an equilibrium is reached 5/16/14 4 4. Osmosis is the diffusion of water molecules directly through the cell's membrane. 5/16/14 5 5. If a cell is in a solution that is….. a) Hypertonic it shrinks (higher concentration of dissolved particles outside than inside of the cell) b) Hypotonic it expands (lower concentration of dissolved particles outside compared with inside of the cell) c) Isotonic no change (same concentration of dissolved particles outside as inside of the cell. 5/16/14 6 Graphic Organizer Hypertonic Hypotonic Isotonic DRAWINGS: For each category, draw a cell in solution. For each picture, show solute particles in your solution and also in your cell. Label solvent line and solute particles. Show if water is entering or leaving the cell using arrows. WRITE ABOUT IT: For each category, answer the following in complete sentences. 1) Is water moving into or out of the cell, or neither? 2) Is the cell shrinking, expanding or staying the same? 3) Are there more solute particles inside 5/16/14the cell or in solution, or neither? 7 Question: What would happen to an animal cell placed into a HYPERtonic solution? 5/16/14 8 (It would shrink- plasmolysis) 6. -
Review Caveolae: Where Incoming and Outgoing Messengers Meet Richard G
Proc. Natl. Acad. Sci. USA Vol. 90, pp. 10909-10913, December 1993 Review Caveolae: Where incoming and outgoing messengers meet Richard G. W. Anderson Department of Cell Biology and Neuroscience, University of Texas Southwestem Medical Center, Dallas, TX 75235 ABSTIRACT Plasmalemmal caveolae ing. At the same time, this information is This portable, membrane-bound com- were flrst identified as an endocytic com- used to construct several models that partment has been found to contain a partment In endothelial cells, where they illustrate the different ways that caveolae number of molecules that are known to appear to move molecules across the cell might function in both intracellular and participate in cell signaling. There are by transcytosis. More recently, they have intercellular communication. three classes of molecules: enzymes that been found to be sites where small mole- generate messengers from substrates in cules are concentrated and internalized by Caveolae the environment, high-affinity binding a process called potocytosis. A growing sites that concentrate chemical signals, body of biochemical and morphological Each caveola is a dynamic piece ofmem- and substrates that are enzymatically evidence indicates that a variety of mole- brane that is either open for receiving and converted into messengers. cules known to function directly or indi- releasing material or closed for process- GPI. Insulin was the first hormone rectly in signal transduction are enriched ing, storage, and delivery to the cell (11). suspected of using inositol phosphogly- in caveolae. This raises the possibility that The exact nature of the closed compart- can (IPG) or a molecule derived from IPG a third function for caveolae is to process ment is still unclear.