SECTION I General Topics
~ '- SECTIONI GeneralTopics
Membrane transport MEMBRANE STRUCTURE What the USMLE Requires You to Know General Features Biologic membranes are bilayers that are assembled from a mixture of lipids and proteins. The i.Factors affecting the rate of diffusion general structure of a membrane is shown in Figure 1-1-1 General charaderistics of Intrinsic protein-mediated transport proteins The differences among the vanous membrane Extracellular transport mechanisms space 0000000000-Hydrophilic er Hydrophobic end Phospholipid 000000000000000 Cytoplasm Figure 1-1-1. The Structure of Biologic Membranes Lipids The lipid component is composed primarily of a bilayer of phospholipids, with the hydrophilic (water-soluble)ends facing the aqueous environment and the hydrophobic(water-insoluble ends facing the interior of the membrane. Other major components include unesterified cholesterol and glycolipid Proteins The proteins are responsible for the dynamic aspects of membrane function. There are two main types of membrane proteins. Integral membrane proteins: They are embedded in the lipid bilayer and cannot be removed without disrupting the bilayer. They include channels, pumps, carriers, and receptors. Peripheral proteins: They bind to the hydrophilic polar heads of the lipids or to the integral proteins. Peripheral proteins contribute to the cytoskeleton and the glycocalyx glycolipid and glycoprotein that cover the cell membrane) KAPLA edical
MembraneTransport MEMBRANESTRUCTURE GeneralFeatures Biologic membranes are bilayers that are assembled from a mixture of lipids and proteins. The general structure of a membrane is shown in Figure I-I-I. Hydrophilice~ Phospholipid Hydrophobic~ Figure 1-1-1.The Structure of Biologic Membranes Lipids The lipid component is composed primarily of a bilayer of phospholipids, with the hydrophilic (water-soluble) ends facing the aqueous environment and the hydrophobic (water-insoluble) ends facing the interior of the membrane. Other major components include unesterified cholesterol and glycolipids. Proteins The proteins are responsible for the dynamic aspects of membrane function. There are two main types of membrane proteins. Integral membrane proteins: They are embedded in the lipid bilayer and cannot be removed without disrupting the bilayer. They include channels, pumps, carriers, and receptors. Peripheral proteins: They bind to the hydrophilic polar heads of the lipids or to the integral proteins. Peripheral proteins contribute to the cytoskeleton and the glycocalyx (glycolipid and glycoprotein that cover the cell membrane). ~ """'" " What the USMLE !,~,!~~,~,~,,!~.~~!5!!~ . Factorsaffectingthe rateof diffusion . General characteristics of protein-mediatedtransport . The differences among the various membrane transport mechanisms meClical 3
USMLE Step 1: Physiology MEMBRANE TRANSPORT Diffusion Factors that affect the rate of diffusion(D)of a substance between two compartments separat ed by a membrane are given in the following formula D∝ △P×SA×So T×VMW AP= concentration gradient across the membrane. The greater the concentration gradient, the ter tbe rate of diffusio SA= surface area of the membrane. The greater the surface area, the greater the rate of diffu sion (For example, exercise opens additional pulmonary capillaries, increasing the surface area for exchange. Emphysema decreases the surface area for exchange. SOL= solubility in the membrane or permeability. The more soluble the substance, the faster it will diffuse. Generally CO, diffuses faster across membranes than O, because CO, exhibits greater solubility T= thickness of the membrane. The thicker the membrane the slower the rate of diffusion (e. g, lung fibrosis) MW =molecular weight. This factor is not important clinically The molecules of eacb species diffuse independently. There is no durect interaction among molecules during diffusion. If the inspired nitrogen in room air is replaced elium, the rate of oxygen and carbon dioxide diffusion will be unaffected Osmosis Osmosis is the diffusion of water across a semipermeable or selectively permeable membrane. Water will diffuse from a region of higher water concentration to a region of lower water con- centration. The water concentration of a solution is determined by the concentration of solute The greater the solute concentration, the lower the water concentration. The basic principles are demonstrated in Figure 1-1-2. 0;0 o;。 Figure 1-1-2 This figure shows two compartments separated by a membrane that is permeable to water but not to solute. Side b has the greater concentration of solute(circles)and thus a lower water con- centration than side A. As a result, water wi diffuse from A to B, and the height of column B will rise, and that of A will fall 4 medical
"... USMLEStep1: Physiology 4 KAPLA~. meulCa I MEMBRANETRANSPORT Diffusion Factors that affectthe rate of diffusion (D) of a substance between two compartments separated by a membrane are given in the following formula: D ex:LlP X SA X SOL T X VMW LlP=concentration gradient across the membrane. The greater the concentration gradient, the greater the rate of diffusion. SA = surface area of the membrane. The greater the surface area, the greater the rate of diffusion. (For example, exerciseopens additional pulmonary capillaries,increasing the surface area for exchange.Emphysema decreases the surface area for exchange.) SOL = solubility in the membrane or permeability. The more soluble the substance, the faster it will diffuse. Generally CO2 diffuses faster across membranes than °2 because CO2 exhibits greater solubility. T = thickness of the membrane. The thicker the membrane, the slower the rate of diffusion, (e.g., lung fibrosis). MW = molecular weight. This factor is not important clinically. The molecules of each species diffuse independently. There is no direct interaction among molecules during diffusion. If the inspired nitrogen in room air is replaced by helium, the rate of oxygen and carbon dioxide diffusion will be unaffected. Osmosis Osmosis is the diffusion of water across a semipermeable or selectivelypermeable membrane. Water will diffuse from a region of higher water concentration to a region of lower water concentration. The water concentration of a solution is determined by the concentration of solute. The greater the solute concentration, the lower the water concentration. The basicprinciples are demonstrated in Figure 1-1-2. A B Figure 1-1-2 This figure shows two compartments separated by a membrane that is permeable to water but not to solute. SideBhas the greater concentration of solute (circles)and thus a lowerwater concentration than side A. As a result, water will diffuse from A to B, and the height of column B will rise, and that of A will fall. I 0 0 I 0 0 I I 0 0 0 0 I 0 0 I I 0 0 I 0 0 I 0 0 I
Membrane transport mOsm(milliosmolar)or mOsm/ =an index of the concentration of particles per liter of solu mM(millimolar)or mML an index of the concentration of molecules dissolved per liter of solution isotonic solutions 300 mOsm= 150 mM NaCl (one NaCl molecule yields two particles 300 mOsm= 300 mM glucose The 300 mOsm is rounded off from the true value of 285 to 290 mOsm PROTEIN (CARRIER)-MEDIATED TRANSPORT Protein carriers transport substances that cannot readily diffuse across a membrane. There are no transporters for gases and other lipid-soluble substances because these substances read penetrate cell membranes. Characteristics Common to All Protein-Mediated Transport Rate of transport: A substance is transported more rapidly than it would be by diffusion, because the membrane is not usually permeable to any substance for which there is a transport protein Saturation kinetics: As the concentration of the substance initially increases on one side of the embrane, the transport rate will increase. Once the transporters become saturated, transport rate is maxima (TM=transport maximum). TM is the transport rate when the carriers are sat- urated. It is directly proportional to the number of functioning transporters Chemical specificity: To be transported, the substance must have a certain chemical structure Generally, only the natural isomer will be transported (e.g., D-glucose but not L-glucose Competition for carrier: Substances of similar chermical structure may compete for the same trans porter. For example, glucose and galactose will generally compete for the same transport protein types of Protein Transport acilitated Transport( Passive Process Net movement is always down a concentration gradient. It is the concentration gradient that drives both facilitated transport and simple diffusion Active Transport(Active Process Net movement is against a concentration gradient Requires chemical energy (ATP) medical 5
..... MembraneTransport mOsm (milliosmolar) or mOsmIL =an index of the concentration of particles per liter of solution. mM (millimolar) or mM/L =an index of the concentration of molecules dissolved per liter of solution. isotonic solutions =300 mOsm = 150 mM NaCl (one NaCl molecule yields two particles in solution). 300 mOsm =300 mM glucose The 300 mOsm is rounded off from the true value of 285 to 290 mOsm. PROTEIN(CARRIER)-MEDIATEDTRANSPORT Protein carriers transport substances that cannot readily diffuse across a membrane. There are no transporters for gases and other lipid-soluble substances because these substances readily penetrate cell membranes. CharacteristicsCommonto All Protein-MediatedTransport Rate of transport: A substance is transported more rapidly than it would be by diffusion, because the membrane is not usually permeable to any substance for which there is a transport protein. Saturation kinetics: As the concentration of the substance initially increases on one side of the membrane, the transport rate will increase. Once the transporters become saturated, transport rate is maximal (TM =transport maximum). TM is the transport rate when the carriers are saturated. It is directly proportional to the number of functioning transporters. Chemical specificity: To be transported, the substance must have a certain chemical structure. Generally, only the natural isomer will be transported. (e.g., D-glucose but not L-glucose). Competition for carrier: Substances of similar chemical structure may compete for the same transporter. For example, glucose and galactose will generally compete for the same transport protein. Typesof ProteinTransport FacilitatedTransport(PassiveProcess) Net movement is always down a concentration gradient. It is the concentration gradient that drives both facilitated transport and simple diffusion. ActiveTransport(ActiveProcess) Net movement is against a concentration gradient Requires chemical energy (ATP) iiieilical 5
USMLE Step 1: Physiology Primary and Secondary Transport In primary active transport, ATP is consumed directly by the transporting protein,(e.g, the Na/K-ATPase pump, or the calcium pump of the sarcolemma). econdary active transport depends indirectly on aTP as a source of energy, as in the cotran port(molecules move in the same direction)of Nat and glucose in the renal tubules and gut This process depends on ATP utilized by the Na/K-ATPase pump. s mucose Lumin Membrane Glucose moved up a concentration adient via secondary activ FIgure 1-1-3 Renal Tubule or Small Intestine Figure 1-1-3 represents a renal proximal tubular cell or a cell lining the small intestine. In this figure, the Na/K-ATPase pump maintains a low intracellular sodium concentration, which cre- ates a large gradient across the cell membrane. It is this sodium gradient across the luminal membrane that drives secondary active transport of glucose In summary, the secondary active transport of glucose Depends upon luminal sodium Is stimulated by luminal sodium(via increased sodium gradient Is linked to the uptake of sodium
r'" USMLEStep1: Physiology 6 meClical Primary and Secondary Transport In primary active transport, ATP is consumed directly by the transporting protein, (e.g., the Na/K-ATPasepump, or the calcium pump of the sarcolemma). Secondary active transport depends indirectly on ATP as a source of energy,as in the cotransport (molecules move in the same direction) of Na+ and glucose in the renal tubules and gut. This process depends on ATP utilized by the Na/K-ATPasepump. ISF Na Na+ Glucose K+ Luminal Membrane Basal Membrane Glucose moved up a concentration gradient via secondary active transport Figure 1-1-3.Renal Tubule or Small Intestine Figure 1-1-3 represents a renal proximal tubular cell or a cell lining the small intestine. In this figure, the Na/K-ATPase pump maintains a low intracellular sodium concentration, which creates a large gradient across the cell membrane. It is this sodium gradient across the luminal membrane that drives secondary active transport of glucose. In summary, the secondary active transport of glucose Depends upon luminal sodium Is stimulated by luminal sodium (via increased sodium gradient) Is linked to the uptake of sodium