Transport Across Cell Membranes Lecture Notes PDF

PAGE 1 https://www.umfst.ro Lecture no2. https://edu.umch.de TRANSPORT ACROSS CELL MEMBRANE 2024 April Lecturer Florina Gliga Summary...

PAGE 1 https://www.umfst.ro Lecture no2. https://edu.umch.de TRANSPORT ACROSS CELL MEMBRANE 2024 April Lecturer Florina Gliga Summary PAGE 2 1.The Cell – Structure and Function. 2. The Plasma Membrane. 3. Transport Across Cell Membranes 4. Basic Principles of Solute and Water Transport 5.Review The Cell – Structure and Functions PAGE 3 Each cell in a human being is a living structure that can survive for months or years, if its surrounding fluids contain appropriate nutrients. Cells provide structure for the body's tissues and organs, ingesting nutrients and converting them to energy, and performing specialized functions. Cells also contain the body's hereditary code that controls the substances synthesized by the cells and permits them to make copies of themselves. The Cell – Structure and Functions PAGE 4 Almost all cells within the human body are divided into two compartments: The nucleus is separated from the cytoplasm by a nuclear membrane – exceptions - the mature human red blood cells and cells within the lens of the eye – they lack the nucleus The cytoplasm is an aqueous solution containing numerous organic molecules, ions, cytoskeletal elements, and a number of organelles. Many of the organelles are membrane- enclosed compartments that carry out specific cellular function. The cytoplasm is separated from the surrounding fluids by a cell membrane, also called the plasma membrane. The Cell – Structure and Functions PAGE 5 Cell components Guyton and Hall Textbook of Medical Physiology, Chapter 2, Copyright © 2016 by Elsevier, Inc. All rights reserved. The Cell – Structure and Functions PAGE 6 Cell components Component Primary Function Metabolism, protein synthesis Cytosol (free ribosomes) Cell shape and movement, Cytoskeleton intracellular transport Genome (22 autosomes and 2 Nucleus sex chromosomes), DNA and RNA synthesis ATP synthesis by oxidative Mitochondria phosphorylation, Ca 2+ storage Smooth endoplasmic Synthesis of lipids, Ca 2+ storage reticulum Translation of mRNA into Free ribosomes cytosolic proteins The Cell – Structure and Functions PAGE 7 Component Primary Function Cell components Translation of mRNA into Rough endoplasmic reticulum membrane associated proteins or for secretion out of the cell Lysosome Intracellular degradation Cellular uptake of cholesterol, uptake of small molecules and Endosome water into the cell, internalization of large particles (e.g., bacteria, cell debris) Modification, sorting, and Golgi apparatus packaging of proteins and lipids for delivery Degradation of intracellular Proteosome proteins Peroxisome Detoxification of substances The Cell – Structure and Functions PAGE 8 Cell components The different substances that make up the cell are collectively called protoplasm. Protoplasm is composed mainly of five basic substances: water, electrolytes, proteins, lipids, and carbohydrates. Water. The principal fluid medium of the cell, in a concentration of 70 to 85 % , (except for fat cells) Contains dissolved chemicals, or suspended as solid particulates. – Chemical reactions take place among the dissolved chemicals or at the surfaces of the suspended particles or membranes. The Cell – Structure and Functions PAGE 9 Cell components Ions. Important ions - potassium, magnesium, phosphate, sulfate, bicarbonate, smaller quantities of sodium, chloride, and calcium. The ions provide inorganic chemicals for cellular reactions and also are necessary for operation of some of the cellular control mechanisms. – E.g. ions acting at the cell membrane are required for transmission of electrochemical impulses in nerve and muscle fibers. The Cell – Structure and Functions PAGE 10 Cell components Proteins. after water, the most abundant substances in most cells are proteins 10 to 20 % of the cell mass. can be divided into two types: structural proteins and functional proteins. Structural proteins mainly in the form of long filaments (polymers of many individual protein molecules) → form microtubules or filamentous tubules - provide the “cytoskeletons” and hold together the cytoplasm. The Cell – Structure and Functions PAGE 11 Cell components The functional proteins entirely different type of protein usually composed of combinations of a few molecules in tubular-globular form often mobile in the cell fluid mainly the enzymes of the cell - come into direct contact with other substances in the cell fluid and catalyze specific intracellular chemical reactions. The Cell – Structure and Functions PAGE 12 Cell components Lipids. insoluble in water, soluble in fat solvents. phospholipids and cholesterol, which together constitute only about 2 % of the total cell mass. – they are mainly are used to form the cell membrane and intracellular membrane barriers and as substrate for some hormone synthesis. triglycerides (in some cells), also called neutral fat. – In the fat cells, triglycerides often account for as much as 95 % of the cell mass - represents the body's main store of energy-giving nutrients. The Cell – Structure and Functions PAGE 13 Cell components Carbohydrates. have little structural function in the cell except as parts of glycoprotein molecules, they play a major role in nutrition of the cell. most human cells do not maintain large stores of carbohydrates – the amount usually averages about 1 % of their total mass , 3 % in muscle cells and, 6 % in liver cells. – glycogen, which is an insoluble polymer of glucose that can transformed in glucose by enzymes → energy needs. however, carbohydrate in the form of dissolved glucose is always present in the surrounding extracellular fluid so that it is readily available to the cell. The Cell – Structure and Functions PAGE 14 The Plasma Membrane Separates the intracellular contents from the extracellular environment. The properties of this membrane, especially the specific membrane proteins →functions: Selective transport of molecules into and out of the cell. A function carried out by membrane transport proteins. Cell recognition through the use of cell surface antigens. Cell communication - neurotransmitter and hormone receptors. Membrane-dependent enzymatic activity. Tissue organization, such as temporary and permanent cell junctions, and interaction with the extracellular matrix, with the use of a variety of cell adhesion molecules. Determination of cell shape by linkage of the cytoskeleton to the plasma membrane. The Cell – Structure and Functions PAGE 15 The Plasma Membrane The cell membrane - a thin, pliable, elastic structure only 7.5 to 10 nanometers thick. It is composed almost entirely of proteins and lipids. The approximate composition – in terms of weight- is proteins 55%; phospholipids 25%; cholesterol 13%; other lipids 4%; and carbohydrates 3%. Also, carbohydrate moieties are attached to the protein molecules on the outside of the membrane and to additional protein molecules on the inside. The Cell – Structure and Functions PAGE 16 The Plasma Membrane Guyton and Hall Textbook of Medical Physiology, Chapter 2, Copyright © 2018 by Elsevier, Inc. All rights reserved. The Cell – Structure and Functions PAGE 17 The Plasma Membrane Phospholipids consist of a phosphorylated glycerol backbone (“head”) and two fatty acid “tails” – the glycerol backbone is hydrophilic (water soluble), – the fatty acid tails are hydrophobic (water insoluble). Thus phospholipid molecules have both hydrophilic and hydrophobic properties and are called amphipathic. The Plasma Membrane PAGE 18 Phospholipid Component of Cell Membranes At an oil-water interface (A) molecules of phospholipids form a monolayer and orient themselves so that the glycerol backbone dissolves in the water phase and the fatty acid tails dissolve in the oil phase. In cell membranes (B ), phospholipids orient so that the lipid-soluble fatty acid tails face each other and the water-soluble glycerol heads point away from each other, dissolving in the aqueous solutions of the ICF or ECF. This orientation creates a lipid bilayer. Costanzo, Linda S., Physiology, Chapter 1, Copyright © 2018 by Elsevier, Inc. All rights reserved. The Plasma Membrane PAGE 19 Phospholipid Component of Cell Membranes The lipid bilayer is not miscible with either the extracellular fluid or the intracellular fluid. Therefore, it constitutes a barrier against movement of water and water-soluble substances between the extracellular and intracellular fluid compartments. – is primarily impermeable to most polar and charged molecules, including ions and large polar molecules – it does allow for the passage of small polar molecules like water - the rate of diffusion through the lipid bilayer alone is relatively slow compared to facilitated diffusion through aquaporins, which significantly enhance the rate of water movement across the membrane. However, lipid soluble substances can penetrate this lipid bilayer, diffusing directly through the lipid substance. The Plasma Membrane PAGE 20 Protein Component of Cell Membranes Proteins in cell membranes - fluid mosaic model. They may be: Integral - they span the membrane Peripheral - they are present on only one side. Costanzo, Linda S., Physiology, Chapter 1, Copyright © 2018 by Elsevier, Inc. All rights reserved. The Plasma Membrane PAGE 21 Protein Component of Cell Membranes 1. Integral membrane proteins are embedded in, and anchored to, the cell membrane by hydrophobic interactions. – to remove an integral protein from the cell membrane, its attachments to the lipid bilayer must be disrupted (e.g., by detergents). their molecular structures interrupt the continuity of the lipid bilayer, constituting an alternative pathway through the cell membrane. many of these penetrating proteins can function as transport proteins. The Plasma Membrane PAGE 22 Protein Component of Cell Membranes Integral membrane proteins Some integral proteins are transmembrane proteins - are in contact with both ECF and ICF. Examples: – transport proteins (e.g., Na + -K + ATPase), – pores, – ion channels, – cell adhesion molecules, – ligand-binding receptors (e.g., for hormones or neurotransmitters), – GTP-binding proteins (G proteins). Other are embedded in the lipid bilayer of the membrane but does not span it. The Plasma Membrane PAGE 23 Protein Component of Cell Membranes Some proteins - have watery spaces all the way through the molecule and allow free movement of water and/or ions or molecules - channel proteins. Carrier proteins - bind with molecules or ions that are to be transported, and through conformational changes in the protein molecules, move the substances through the interstices of the protein to the other side of the membrane. Both of them are usually selective for the types of molecules or ions that are allowed to cross the membrane. The Plasma Membrane PAGE 24 Protein Component of Cell Membranes Guyton and Hall Textbook of Medical Physiology, Chapter 4, Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. The Plasma Membrane PAGE 25 Protein Component of Cell Membranes Peripheral membrane proteins are not embedded in the membrane and are not covalently bound to cell membrane components. are loosely attached to the intra - or extracellular side of the cell membrane by electrostatic interactions (e.g., with integral proteins). – One example of a peripheral membrane protein is ankyrin, which “anchors” the cytoskeleton of red blood cells to an integral membrane transport protein  PAGE 26 Transport Across Cell Membranes The normal function of cells requires the continuous movement of water and solutes into and out of the cell. The intracellular and extracellular fluids are composed primarily of H2O, in which solutes (e.g., ions, glucose, amino acids) are dissolved. The plasma membrane, with its hydrophobic core, is an effective barrier to the movement of virtually all of these biologically important solutes. It also restricts the movement of water across the membrane. The presence of specific membrane transporters in the membrane is responsible for the movement of these solutes and water across the membrane.  PAGE 27 Transport Across Cell Membranes However, the presence of a pathway is not sufficient for transport to occur; an appropriate driving force is also required to move the solutes: – diffusion, – osmosis, – active and passive transport. Substances can be transported: down an electrochemical gradient (downhill) - diffusion, either simple or facilitated against an electrochemical gradient (uphill) - by active transport, which may be primary or secondary  PAGE 28 Transport Across Cell Membranes Membrane transporters proteins may be divided into four general groups: water channels, ion channels, solute carriers, and adenosine triphosphate (ATP)–dependent transporters. Class Transport Mode Transport Rate Pore Open (not gated) Up to 10 9 molecules/sec Channel Gated 10 6 -10 8 molecules/sec Solute carrier Cycle 10 2 -10 4 molecules/sec ATP-dependent Cycle 10 2 -10 4 molecules/sec Transport Across Cell Membranes PAGE 29 1.Water Channels Water channels, or aquaporins (AQPs), are the main routes for water movement into and out of the cell. They are widely distributed throughout the body (e.g., the brain, lungs, kidneys, salivary glands, gastrointestinal tract, and liver). Some isoforms also provide a pathway for other molecules such as glycerol, urea, mannitol, purines, pyrimidines, CO 2 , and NH 3 to cross the membrane. Transport Across Cell Membranes PAGE 30 1.Water Channels Cells express different AQP isoforms, and some cells even express multiple isoforms. Regulation of the amount of H 2O that can enter or leave the cell via AQPs occurs primarily by altering the number of AQPs in the membrane. Guyton and Hall Textbook of Medical Physiology, Copyright © 2016 by Elsevier, Inc. All rights reserved. Transport Across Cell Membranes PAGE 31 2. Ion channels Ion channels are found in all cells, and are especially important for the function of excitable cells (e.g., neurons and muscle cells). Ion channels are classified by their selectivity, conductance and mechanism of channel gating (i.e., opening and closing). Selectivity is defined as the nature of the ions that pass through the channel. – highly selective - they allow only a specific ion through. – nonselective - allowing all or a group of cations or anions through. Channel conductance refers to the number of ions that pass through the channel Transport Across Cell Membranes PAGE 32 2.Ion channels Ion channels fluctuate between an open state or a closed state, a process called gating. Factors that can control gating include: – membrane voltage, – extracellular agonists or antagonists (e.g., acetylcholine), – intracellular messengers (e.g., Ca ++ , ATP, cyclic guanosine monophosphate), – mechanical stretch of the plasma membrane. Ion channels can be regulated by a change in the number of channels in the membrane or by gating of the channels. Transport Across Cell Membranes PAGE 33 Ion channels Pope, Simon, Medical Biochemistry, Copyright © 2019, Elsevier Limited. Costanzo, Linda S., Physiology, Copyright © 2018 by Elsevier, Inc. All rights reserved. Transport Across Cell Membranes PAGE 34 Ion Movement There are three factors that can induce the movement of the ions through ion channels: The concentration gradient – a difference in concentration of the ion on the two sides of the membrane →from higher concentration to lower concentration. The electrical gradient – an electrical potential difference across the membrane defined as the electrical potential value inside the cell relative to the extracellular environment. Positive ions will be attracted to negative electrical potential and repelled from positive electric potential, and vice versa. Active Transport. Transport Across Cell Membranes PAGE 35 Guyton and Hall Textbook of Medical Physiology, Chapter 4, Copyright © 2016 by Elsevier, Inc. All rights reserved.  Transport Across Cell Membranes PAGE 36 3. Active transport - Adenosine Triphosphate–Dependent Transporters Active transport – use the energy in ATP to drive the movement of molecules/ions across the membrane. – sodium, potassium, calcium, hydrogen, chloride, and a few other ions. At times, a large concentration of a substance is required in the intracellular fluid even though the extracellular fluid contains only a small concentration. This situation is applicable, for instance, for K+ and Na+ ions.  Transport Across Cell Membranes PAGE 37 3. Active transport - Adenosine Triphosphate–Dependent Transporters Na + ,K + -ATPase is an important example of a P-type ATPase. With the hydrolysis of each ATP molecule, it transports three Na + ions out of the cell and two K + ions into the cell. Neither of these two effects could occur by simple diffusion that eventually equilibrates concentrations on the two sides of the membrane. When a cell membrane moves molecules or ions “uphill” against a concentration gradient (or “uphill” against an electrical or pressure gradient), the process is called active transport Transport Across Cell Membranes PAGE 38 3. Active transport When 2 K+ ions bind on the outside of the carrier protein and 3 Na+ ions bind on the inside, the ATPase function of the protein becomes activated. Activation of the ATPase function leads to cleavage of one molecule of ATP, splitting it to adenosine diphosphate (ADP) and liberating a high-energy phosphate bond of energy. This liberated energy is then believed to cause a chemical and conformational change in the protein carrier molecule, extruding the Guyton and Hall Textbook of Medical Physiology, Chapter 4, three Na+ ions to the outside and the two K+ Copyright © 2016 by Elsevier, Inc. All rights reserved. ions to the inside.  Transport Across Cell Membranes PAGE 39 3. Active transport - Adenosine Triphosphate–Dependent Transporters Na + ,K + -ATPase is present in all cells and plays a critical role in establishing cellular ion and electrical gradients, as well as maintaining cell volume. – responsible for maintaining the Na+ and K+ concentration differences across the cell membrane, as well as for establishing a negative electrical voltage inside the cells. – is also the basis of nerve function, transmitting nerve signals throughout the nervous system. Transport Across Cell Membranes PAGE 40 3. Active transport The fact that the Na+ -K+ pump moves three Na+ ions to the exterior for every two K+ ions that are moved to the interior means that a net of one positive charge is moved from the interior of the cell to the exterior for each cycle of the pump. Therefore, the Na+ -K+ pump is said to be electrogenic because it creates an electrical potential across the cell membrane. Transport Across Cell Membranes PAGE 41 3. Active transport Another important primary active transport mechanism is the calcium pump. Calcium ions are normally maintained at an extremely low concentration in the intracellular cytosol of virtually all cells in the body, at a concentration about 10.000 times less than that in the extracellular fluid. This level of maintenance is achieved mainly by two primary active transport calcium pumps. Transport Across Cell Membranes PAGE 42 3. Active transport Primary active transport of hydrogen ions is important at two places in the body: (1) in the gastric glands of the stomach (2) in the distal tubules and cortical collecting ducts of the kidneys. Transport Across Cell Membranes PAGE 43 4. Solute Carriers - secondary transport Solute carriers represent a large group of membrane transporters categorized into more than 50 families; almost 400 specific transporters have been identified to date. These carriers can be divided into three groups according to their mode of transport. 1. Uniporters (or facilitated transporters ), transports a single molecule across the membrane. The transporter that brings glucose into the cell (glucose transporter 1 GLUT-1) is an important member of this group. Transport Across Cell Membranes PAGE 44 4. Solute Carriers 2. Symporters (or cotransporters ), couples the movement of two or more molecules/ions across the membrane in the same direction. – The Na + ,K + ,2Cl − (NKCC) symporter found in the kidney, which is crucial for diluting and concentrating the urine is a member of this group. 3. Antiporters (or exchange transporters ), also couples the movement of two or more molecules/ions across the membrane in opposite directions. – The Na + -H + antiporter is found in all cells and plays an important role in regulating intracellular pH.  Transport Across Cell Membranes PAGE 45 4. Solute Carriers Symporters For Na+ to pull another substance along with it, a coupling mechanism is required. The carrier in this instance serves as an attachment point for both the Na+ ion and the substance to be co-transported. Once they both are attached, the energy gradient of the Na+ ion causes both the Na+ ion and the other substance to be transported together to the interior of the cell. Guyton and Hall Textbook of Medical Physiology, Chapter 4, 47-59 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved.  PAGE 46 Transport Across Cell Membranes In counter-transport, Na+ ions again attempt to diffuse to the interior of the cell because of their large concentration gradient. However, this time, the substance to be transported is on the inside of the cell and must be transported to the outside. Once both have become bound, a conformational change occurs, and energy released by the action of the Na+ ion moving to the interior causes the Guyton and Hall Textbook of Medical Physiology, Chapter 4, other substance to move to the exterior. Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Transport Across Cell Membranes PAGE 47 Cell Biology, Pollard, Thomas. © 2023. Basic Principles of Solute and Water Transport PAGE 48 Diffusion Diffusion - random molecular movement of substances molecule by molecule. Diffusion - molecules move spontaneously from an area of high concentration to one of low concentration. All molecules and ions in the body fluids (liquids or in gases ), including water molecules and dissolved substances, are in constant motion, with each particle moving its separate way.  Basic Principles of Solute and Water Transport PAGE 49 Diffusion A single molecule in a solution bounces among the other molecules, first in one direction, then another, then another, and so forth, randomly bouncing thousands of times each second. Guyton and Hall t © 2016 by Elsevier, Inc. All rights reserved. Basic Principles of Solute and Water Transport PAGE 50 Diffusion The rate of diffusion depends on: 1. concentration difference between the two sides of the membrane 2. the electrical charge 3. the solubility of the particle in the solvent; if it is not very soluble the concentration will be low 4. the size of the solute particle (small particles will diffuse faster than large particles) 5. temperature: diffusion is faster at high temperatures than at low temperatures; body temperature is about 37°C in normal human subjects. The motion never ceases except at absolute zero temperature. 6. the shape/ the weight of the particle 1,2 - electrochemical gradient Basic Principles of Solute and Water Transport PAGE 51 Diffusion Diffusion through the cell membrane - two subtypes: Simple diffusion means that kinetic movement of molecules or ions occurs through a membrane without any interaction with carrier proteins in the membrane. Facilitated diffusion requires interaction of a carrier protein. The carrier protein aids passage of the molecules or ions through the membrane by binding chemically with them. Basic Principles of Solute and Water Transport PAGE 52 Diffusion Simple diffusion can occur through the cell membrane by two pathways: 1.1. through the interstices of the lipid bilayer if the diffusing substance is lipid soluble Oxygen, carbon dioxide, and other gases diffuse freely across membranes. An important factor that determines how rapidly a substance diffuses through the lipid bilayer is the lipid solubility of the substance. 1.2 through watery channels that penetrate all the way through some of the large transport proteins aquaporins. – The total amount of water that diffuses in each direction through the red blood cell membrane during each second is about 100 times as great as the volume of the red blood cell itself. Basic Principles of Solute and Water Transport PAGE 53 Diffusion 1.3 Other lipid-insoluble molecules can pass through the protein pore channels in the same way as water molecules if they are water soluble and small enough. However, as they become larger, their penetration falls off rapidly. For instance, the diameter of the urea molecule is only 20 % greater than that of water, yet its penetration through the cell membrane pores is about 1000 times less than that of water. Basic Principles of Solute and Water Transport PAGE 54 Diffusion 1.2 Ions diffuses across the membrane using the ion chanels protein transporter Guyton and Hall Textbook of Medical Physiology, Chapter 4, Copyright © 2016 by Elsevier, Inc. All rights reserved. Basic Principles of Solute and Water Transport PAGE 55 Facilitated diffusion Facilitated diffusion (carrier-mediated diffusion) - a substance transported/diffuses through the membrane with the help of a specific carrier protein. Guyton and Hall Textbook of Medical Physiology, Chapter 4, 47-59 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Basic Principles of Solute and Water Transport PAGE 56 Facilitated diffusion Facilitated diffusion differs from simple diffusion: – Although the rate of simple diffusion through an open channel increases proportionately with the concentration of the diffusing substance, in facilitated diffusion the rate of diffusion approaches a maximum, called Vmax, as the concentration of the diffusing substance increases. – Vmax is dependent on the protein carrier density in the membrane – Among the many substances that cross cell membranes by facilitated diffusion are glucose and most of the amino acids.  PAGE 57 The figure shows that as the concentration of the diffusing substance increases, the rate of simple diffusion continues to increase proportionately, but in the case of facilitated diffusion, the rate of diffusion cannot rise greater than the Vmax level. Guyton and Hall Textbook of Medical Physiology, Chapter 4, 47-59 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Basic Principles of Solute and Water Transport PAGE 58 Osmosis By far the most abundant substance that diffuses through the cell membrane is water. Under certain conditions, a concentration difference for water can develop across a membrane → net passive movement of water from low solute towards a high solute concentration (osmotic pressure difference ). The cell either swell or shrink, depending on the direction of the water movement. The movement of water across cell membranes occurs by the process of osmosis.  PAGE 59 Guyton and Hall Textbook of Medical Physiology, Chapter 4, Copyright © 2016 by Elsevier, Inc. All rights reserved. Basic Principles of Solute and Water Transport PAGE 60 Osmotic pressure is determined by the number of solute molecules dissolved in the solution. is not dependent on such factors as the size of the molecules, their mass, or their chemical nature (e.g., valence). The amount of pressure required to stop osmosis is called the osmotic pressure. The principle of a pressure difference opposing osmosis is demonstrated in the next figure, which shows a selectively permeable membrane separating two columns of fluid, one containing pure water and the other containing a solution of water and any solute Basic Principles of Solute and Water Transport PAGE 61 Osmosis Berne and Levy Physiology, 1, 2-16 Copyright © 2018 by Elsevier, Inc. All rights reserved Basic Principles of Solute and Water Transport PAGE 62 Osmosis Schematic representation of osmotic water movement and the generation of an osmotic pressure. Compartment A and compartment B are separated by a semipermeable membrane. Compartment A contains a solute, that will not penetrate the membrane. Compartment B contains only distilled water. Over time, water moves by osmosis from compartment B to compartment A down to its concentration gradient. This causes the level of fluid to be raised in compartment A and lowered in compartment B. At equilibrium, the hydrostatic pressure exerted by the column of water (h) stops the net movement of water from compartment B to A. Thus at equilibrium, the hydrostatic pressure is equal and opposite to the osmotic pressure exerted by the solute particles in compartment A. Basic Principles of Solute and Water Transport PAGE 63 Transport across the cell membrane Uses Carrier- Dependent on Na + Type of Transport Active or Passive Metabolic Mediated Gradient Energy Simple diffusion Passive; downhill No No No Facilitated Passive; downhill Yes No No diffusion Primary active Active; uphill Yes Yes; direct No transport Yes (solutes move in Cotransport Secondary active Yes Yes; indirect same direction as Na + across cell membrane) Yes (solutes move in Countertransport Secondary active Yes Yes; indirect opposite direction as Na + across cell membrane) Basic Principles of Solute and Water Transport PAGE 64 Transport across the cell membrane Seifter, Julian, Integrated Physiology and Pathophysiology© 2022. References PAGE 65 1. Berne and Levy Physiology, Koeppen, Bruce M., MD, PhD; Stanton, Bruce A., PhD. Published January 1, 2018 2. Guyton and Hall, Textbook ot Medical Physiology thirteen edition, John E. Hall 3. Linda S. Constanzo, Physyology Sixth Edition 4. Boron, Walter F., MD, PhD; Boulpaep, Emile L., MD, Medical Physiology, Third Edition, 5. Netter's Essential Physiology, Mulroney, Susan E., PhD; Myers, Adam K., PhD. Published January 1, 2016