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Transport across cell membrane (2) Ahmed Saleh Hudna Assistant Professor of Pediatrics, UST [email protected]  Transport across cell membrane Referenc  The course title: Introduction to Physiolog...

Transport across cell membrane (2) Ahmed Saleh Hudna Assistant Professor of Pediatrics, UST [email protected]  Transport across cell membrane Referenc  The course title: Introduction to Physiology e  Course code: BMD 06  Faculty: Faculty of Medicine and Health Sciences  Department: Physiology Department  Program: Bachelor of Medicine and Surgery  Lecturer: Ahmed Hudna, Assistant professor of pediatrics, UST, Sana’a  Contact: [email protected]  Transport across cell membrane The student at the end of lecture should be able to Define types of transport across cell membrane Explain the passive transport and its types Mention the active transport and its types Describe some example of each type Transport across cell membrane Content Types of transport Passive transport Active transport Transport across cell membrane Introduction Lipid bilayer: - barrier against movement of water molecules and water soluble substances - permit lipid-soluble substances to diffuse. Membrane protein: - function as transport proteins. - channel proteins: free movement of water or ion with kinetic motion - carrier proteins: ions or molecules with conformational changes in the protein molecules. Transport across cell membrane Introduction Transport through the cell membrane: Simple transport: through the membrane or by a carrier protein, with a concentration gradient without using an energy Active transport: a carrier protein against a concentration gradient requires an energy Transport across cell membrane Simple transport 2 types: - Simple diffusion - Facilitated diffusion.  Transport across cell membrane SIMPLE DIFFUSION - Definition: movement of molecules without carrier proteins. - simple diffusion eventually equilibrates concentrations on the two sides of the membrane (maintain equilibrium) - Two pathways: o lipid-soluble substance through the lipid bilayer. (oxygen, nitrogen, carbon dioxide) o diffusion of water and other lipid-insoluble molecules through protein channels. water pass through protein “pores” called aquaporins. Aquaporins have a narrow pore that only permits water molecules to diffuse through the membrane. - Depend on: amount of substance, the velocity of motion, lipid solubilities, and the number and sizes of openings in the membrane. Transport across cell membrane SIMPLE DIFFUSION Example: - 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 - 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. Transport across cell membrane Facilitated diffusion Also called: - carrier-mediated diffusion - Gating of channels It requires interaction of a carrier protein. There is a binding receptor on the inside of the protein carrier. Depend on: - diameter or shape of a pore - its electrical charges Transport across cell membrane Facilitated diffusion The protein channels had two important characteristics: - Selectively permeable to certain substances; - Gates are controlled in two principal ways: 1. Voltage gating: depend on the electrical potential across the cell membrane. 2. Chemical (ligand) gating: a chemical substance (a ligand) causes a chemical change in the protein that opens or closes the gate, e.g., Acetylcholine on the acetylcholine receptor. Transport across cell membrane Facilitated diffusion The difference between simple diffusion and facilitated diffusion: 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 higher than the maximum concentration Vmax level. Example: - Glucose transporter 4 (GLUT4), is activated by insulin, which can increase the rate of facilitated diffusion of glucose as much as 10- to 20-fold in insulin-sensitive tissues. - Potassium channels permit passage of potassium ions across the cell membrane about 1000 times more readily than they permit passage of sodium ions. Transport across cell membrane Factors that affect the rate of diffusion 1- Permeability of the membrane and is affected by:  Thickness of the membrane.  Lipid solubility.  Number of protein channels.  Temperature.  Molecular weight of diffusing substance. 2- Surface area of the membrane. 3- Concentration difference (gradient). 4- Electrical potential. 5- Pressure difference (Pressure gradient). Transport across cell membrane OSMOSIS The movement of water caused by a concentration difference of water is called osmosis - the most abundant substance that diffuses through the cell membrane is water. Enough water ordinarily diffuses in each direction through the red blood cell membrane per second to equal about 100 times the volume of the cell itself. The amount diffuses in the two directions is balanced so precisely that zero net movement of water occurs. The volume of the cell remains constant.. Transport across cell membrane OSMOSIS Osmotic Pressure: The amount of pressure required to stop osmosis, is determined by the number of particles per unit volume of fluid To express the concentration of a solution in terms of numbers of particles, a unit called the osmole is used in place of grams. One osmole is 1 gram molecular weight of osmotically active solute. Thus, 180 grams of glucose, which is 1 gram molecular weight of glucose, is equal to 1 osmole of glucose because glucose does not dissociate into ions. The normal osmolality of the extracellular and intracellular fluids is about 300 milliosmoles per kilogram of water.  Transport across cell membrane OSMOSIS Osmolarity is the osmolar concentration expressed as osmoles per liter of solution rather than osmoles per kilogram of water. it is osmoles per kilogram of water (osmolality) that determines osmotic pressure, the quantitative differences between osmolarity and osmolality are less than 1% for dilute solutions such as those in the body. Because it is far more practical to measure osmolarity than osmolality, measuring osmolarity is the usual practice in physiological studies. Transport across cell membrane ACTIVE TRANSPORT  Need energy  Need a carrier protein  moving molecules or ions against a concentration gradient or against an electrical or pressure gradient.  Examples: sodium, potassium, calcium, hydrogen, iron, chloride, iodide, and urate ions, several different sugars, and most of the amino acids. Transport across cell membrane ACTIVE TRANSPORT  Divided into 2 types according to the source of the energy used to facilitate the transport:  PRIMARY ACTIVE TRANSPORT: energy is derived directly from the breakdown of adenosine triphosphate (ATP)  SECONDARY ACTIVE TRANSPORT: the energy is derived secondarily from stored energy created originally by primary active transport (in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane) Transport across cell membrane ACTIVE TRANSPORT  Primary active transport: 1. Na- k pump 2. Calcium pump 3. Hydrogen pump  Secondary active transport: 1. Co-transport: sodium-glucose cotransport 2. Counter-transport: sodium-calcium counter- transport and sodium-hydrogen counter-transport  Transport across cell membrane PRIMARY ACTIVE TRANSPORT Sodium-Potassium Pump Transports: transport of sodium outward the cell and pumps potassium from the outside to the inside. Role: - maintaining the sodium and potassium concentration differences across the cell membrane - establishing a negative electrical voltage inside the cells. (creates positivity outside the cell and a negativity on the inside with a negative charge of protein inside the cell) - This pump is also the basis of nerve function, transmitting nerve signals throughout the nervous system. Transport across cell membrane PRIMARY ACTIVE TRANSPORT The carrier protein of the Na+-K+ pump is a complex of two separate globular proteins: - a larger one called the α subunit (molecular weight of 100,000) - a smaller one called the β subunit (molecular weight of 55,000). Role: of larger protein: 1. It has three binding sites for sodium ions on the portion of the protein that protrudes to the inside of the cell. 2. It has two binding sites for potassium ions on the outside. 3. The inside portion of this protein near the sodium binding sites has adenosine triphosphatase (ATPase) activity. Transport across cell membrane Sodium-Potassium Pump Transports When two potassium ions bind on the outside of the carrier protein and three sodium 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 causes a chemical and conformational change in the protein carrier molecule, extruding three sodium ions to the outside and two potassium ions to the inside. Transport across cell membrane Sodium-Potassium Pump Transports One of the most important functions of the Na+-K+ pump is to control the cell volume. Without function of this pump, most cells of the body would swell until they burst. Most of intracellular proteins are negatively charged and attract large numbers of potassium, sodium, and other positive ions. All these molecules and ions then cause osmosis of water to the interior of the cell. Unless this process the cell will swell until it bursts. The normal mechanism for preventing this outcome is the Na+- K+ pump. Transport across cell membrane CALCIUM PUMPS Primary active transport. Two calcium pumps: 1. in the cell membrane: pumps calcium to the outside of the cell. 2.The other pumps calcium ions into one or more of the intracellular vesicular organelles of the cell, such as the sarcoplasmic reticulum (Specialized Endoplasmic Reticulum of Skeletal Muscle) and the mitochondria in all cells. The intracellular calcium is 10,000 times less than that in the extracellular fluid. In each of these cases, the carrier protein functions as an enzyme ATPase. Transport across cell membrane Hydrogen ion pump Primary active transport of hydrogen ions in two places: - in the gastric glands of the stomach - in the late distal tubules and cortical collecting ducts of the kidneys. At the secretory ends of the gastric gland parietal cells, the hydrogen ion concentration is increased as much as a million-fold and then is released into the stomach, along with chloride ions, to form hydrochloric acid. In the distal renal tubules, large amounts of hydrogen ions are secreted from the blood into the renal tubular fluid for the purpose of eliminating excess hydrogen ions from the body fluids. The hydrogen ions can be secreted into the renal tubular fluid against a concentration gradient of about 900-fold. most of these hydrogen ions combine with tubular fluid buffers before they are eliminated in the urine  Transport across cell membrane SECONDARY ACTIVE TRANSPORT Two types: 1. CO-TRANSPORT: the diffusion energy of sodium can pull other substances along with the sodium through the cell membrane. Example: Glucose and many amino acids 2. COUNTER-TRANSPORT: 2 ions in different surface of carrier and move one counter the other.example: sodium-calcium counter-transport and sodium- hydrogen counter-transport  Transport across cell membrane SECONDARY ACTIVE TRANSPORT Sodium-calcium counter-transport: sodium ions moving to the interior and calcium ions to the exterior; both are bound to the same transport protein in a counter-transport mode. Sodium-hydrogen counter-transport: in theproximal tubules of the kidneys, where sodium ions move from the lumen of the tubule to the interior of the tubular cell and hydrogen ions are counter-transported into the tubule lumen. Transport across cell membrane Other active transport Endocytosis Exocytosis Pinocytosis Phagocytosis is active process large particles a process by (energy and (e.g. proteins) means of which Ca++) can cross cell bacteria and secretory membranes. dead tissue are granules are engulfed by cells. extruded out of the cell.