Cellular Biology: 1.3 Transport of Substances Through Cell Membrane PDF

# Cellular Biology: The Cellular Environment, Fluids and Electrolytes, Acids and Bases ## **1.3 Transport of Substances Through Cell Membrane** (Guyton CH 4) ### **Motile Cilia** - Involves rapid whip-like strokes to propel mucus or ova, followed by slower recovery movements (10-20 per sec). - **In...

# Cellular Biology: The Cellular Environment, Fluids and Electrolytes, Acids and Bases ## **1.3 Transport of Substances Through Cell Membrane** (Guyton CH 4) ### **Motile Cilia** - Involves rapid whip-like strokes to propel mucus or ova, followed by slower recovery movements (10-20 per sec). - **Inhibited by smoking.** - **Ex:** Found in respiratory airways (mucus movement) and fallopian tubes (moves the ovum). - Powered by dynein motor proteins and ATP. ### **Non-motile** - Primary cilia serve as sensory structures (e.g., in kidney epithelial cells for detecting fluid flow). - Defects in signaling by primary cilia in renal tubular epithelial cells are thought to contribute to various disorders, including: - polycystic kidney disease. ### **Key Concepts** - **Chemotaxis:** Chemical signaling molecules direct cell movement. - **Autophagy:** Cellular process for degrading and recycling damaged organelles or large protein aggregates. - **ATP:** The primary energy currency, critical for cellular metabolism and function. - **Plasma Membrane:** Selectively permeable barrier essential for maintaining cellular homeostasis and communication. ## **Transport of Substances Through Cell Membranes** - Intracellular and extracellular fluid concentration differences are extremely important to life of the cell. - Extracellular fluid has a large amount of sodium, but only a small amount of potassium. - Extracellular fluid has a large amount of chloride, but very little intracellular. ### **Ion Concentration NEED TO KNOW** | Ion | Extracellular (mEq/L) | Intracellular (mEq/L) | |--------------|-------------------------|-------------------------| | Na+ | 142 | 10 | | K+ | 4 | 140 | | Ca2+ | 2.4 | 0.0001 | | Mg2+ | 1.2 | 58 | | Cl- | 103 | 4 | | HCO3- | 24 | 10 | | Phosphates | 4 | 75 | | SO42- | 1 | 2 | | Glucose | 90 mg/dl | 0 to 20 mg/dl | | Amino acids | 30 mg/dl | 200 mg/dl? | | Cholesterol | 0.5 g/dl | -- | | Phospholipids | -- | 2 to 95 g | | Neutral fat | -- | -- | | PCO2 | 35 mm Hg | 20 mm Hg? | | pH | 7.4 | 7.0 | | Proteins | 2 g/dl (5 mEq/L) | 16 g/dl (40 mEq/L) | - https://images.app.goo.gl/d45NyFgxeyurMnwk6 - 80% of ATP usage is to transport substances through cells. ### **Cell Membrane** - The cellular membrane is made of a lipid bilayer, which is an antipathic molecule. - **Polar and hydrophilic on the exterior.** - **Non-polar and lipophilic on the interior.** - **It is impenetrable to polar or hydrophilic substances.** - Does not allow mixing of intracellular and extracellular fluid. - **Lipid soluble** - diffuse directly though lipid bilayer (substrate). ### **Integral Proteins** - Penetrating proteins can serve as transport proteins. ### **Channel Proteins** - Watery spaces all the way through to allow for diffusion. ### **Carrier Proteins** - Bind with molecules or ions → a conformational change allows the movement of substances through the membrane. ## **Transport Through The Cell Membrane:** - Movement thought the membrane can occur via these 2 mechanisms - **Diffusion:** - The random molecular movement of substances, molecule by molecule, either through intermolecular spaces or in combination with a carrier protein. - Follows concentration gradient. - **Ex:** open channel for NA to pass only down conc. gradient. - **Active Transport:** - The movement of ions or other substances across the membrane in combination with a carrier protein. - A substance to moves against an energy gradient. - **EX:** low to High concentration - Requires additional energy. ## **Diffusion:** - **Energy:** - All molecules are in constant motion. - **Simple Diffusion:** - Simple diffusion is kinetic movement that occurs through a membrane opening or through intermolecular spaces without interaction with carrier proteins. - Can occur through the lipid bilayer if the substance is lipid soluble. - Can also occur through a watery channel that penetrates through the membrane. - **Ex:** CO2 is much higher. - **Facilitated Diffusion:** - Facilitated diffusion requires a carrier protein. - Carrier proteins bind and shuttle molecules or ions through the membrane. ## **Diffusion of Lipid Soluble Substances:** - **Rate of Diffusion:** - Lipid soluble substances can move through the lipid bilayer. - The rate of diffusion is directly proportional to their lipid solubility. - Oxygen's lipid solubility is high. - Therefore, it can be delivered to the interior of the cell. - CO2 is also lipid soluble, but to a much greater degree than 02. ## **Diffusion of Lipid Insoluble Molecules:** - **Protein Channels:** - The diffusion of lipid insoluble molecules occurs through protein channels that penetrate all the way through the membrane. - **Ex:** Water is a prime. - **Even though water is highly insoluble in lipids, it passes through the protein channels that are called aquaporins.** - **Aquaporins:** - Aquaporins are pores that selectively permit rapid passage of water through the membrane. - There are at least 13 different types of aquaporins in mammals. - **Rapid Diffusion:** - Water diffuses at an astounding rate through them. - **Ex:** The amount of water that diffuses through a red blood cell each second is 1000 times greater than its volume. ## **Diffusion of Molecules Through the Lipid Bilayer:** - Diffusion of molecules through the lipid bilayer is affected by multiple characteristics. - Hydrophobic or lipid soluble molecules readily diffuse. - Large, uncharged molecules cannot pass. - Charged ions cannot pass. - **It's important to point out that charged ions are water soluble (hydrophilic).** ## **Selective Permeability of Pores and Channels:** - **Pores are integral cell membrane proteins** - Form open tubules through the membrane and are always open. - The diameter of a pore and its electrical charge provide selectivity to only certain molecules. - **EX:** aquaporins have a narrow pore that permits water to pass single file, but is too narrow for any hydrated ions. - **Protein Channels** - Protein channels are different from pores. - Selectively permeable to certain substances. - Many of the channels can also be open or closed by gates. - **Ligand Gated** - Ligand gated are regulated by chemicals that bind to the channel. - **Voltage Gates** - Voltage gated are regulated by electrical signals. ## **Selective Permeability of Proteins Channels** - Protein channels are porous, with specific characteristics that allow them to be highly selective for the transport of one or more specific ion or molecule. - This results from specific characteristics of the channel, such as diameter, shape, electrical charge, and chemical bonds. - **Characteristics:** - Diameter - Shape - Electrical Charge - Chemical Bonds - **EX:** potassium channels permit potassium passage 1000 times more readily than sodium ions. - At the top of the pore, loops provide a selectivity filter. - Carbonyl oxygens dehydrate the potassium ions, allowing them to pass the dehydrated potassium through the channel. - They're too far apart to dehydrate the smaller sodium ions and therefore remain hydrated and unable to pass. - **Gating of Protein Channels:** - **Control Ion permeability** - The gating of protein channels provides a means of controlling ion permeability. - Some gates are thought to be extensions of the protein molecule, which can be closed or lifted away by a conformational change in the shape of the protein molecule. ## **Gates** - **Voltage gated** - With voltage gated channels. The animal protein responds to the electrical potential across the cell membrane. - When the inside of the cell loses its charge, the gate opens to allow ions to pass. - This opening is in all or none fashion, with each state lasting only a fraction of a millisecond. - **Chemical (ligand) gated** - Chemical or ligand gating is when a chemical substance or ligand causes a conformational change in the molecule. - **Acetylcholine Receptor** - One of the most important ligands is the neurotransmitter acetylcholine on the acetylcholine receptor. - This is a negatively charged pore which acetyl choline opens. - It allows uncharged or positive particles smaller than 0.65 nm to pass. - This is an extremely important gate for the transmission of nerve cell signals. ## **Facilitated Diffusion** - Carrier mediated diffusion aka facilitated diffusion. - When a substance diffuses through the membrane with the help of a specific carrier protein. - **EX:** glucose and insulin. - **Rate of Diffusion is proportional to the concentration of the substance.** - **Although there is a maximum rate** - The rate is limited by the rate at which carrier protein can undergo changes back and forth between states, which is Vmax. - Carrier proteins can allow the molecule to move in either direction. - Binding of the receptor inside the protein carrier is weak, and thermal motion causes it to break away once opening to the inside has occurred. ## **Factors that effect net diffusion rate** - **Molecular Movement** - Molecular movement is constant. - Occurs in either direction. - Diffusion is proportional to the concentration differences across the membrane. - **Electrical Gradient** - An electrical gradient will cause increased diffusion of opposite charges. - Creating a concentration gradient. - When this gradient is strong enough, the concentration gradient will pose the electrical gradient and a balance will be reached. - The Nernst equation is used to calculate this balance = Electromotive Force - The Nernst equation is important for nerve impulses. - **Electrical gradient** - EMF=±61/z x log Cinside/Coutside - **Pressure across membrane** - Pressure across the membrane is created by more molecules striking the semi-permeable membrane on one side. - This increase is the amount of energy and causes of movement of molecules from the high pressure side to the low pressure side. - The three factors that affect the net diffusion across a semi-permeable membrane are: 1. Concentration 2. Electrical Potential 3. Pressure. - All these factors are seeking equilibrium. ## **Osmosis Across Selectively Permeable Membranes** - Water is the most abundant substance that diffuses through a cell membrane, BUT balance is so precise that little to zero net movement occurs. - **Osmosis** - When a concentration difference develops, the net movement of water occurs. - Causing the cell to swell or shrink. - **Osmotic pressure** - Osmotic pressure is the pressure required to stop osmosis. - Osmotic pressure is created by the number of particles, not by the mass of the particles. **COLIGITIVE properties of chemistry** - Large particles have a greater mass but also move at a slower velocity - So the average kinetic energy is the same. - **Molar Concentration** - The concentration of a solution in terms of number of particles, and osmosis is an expression of the concentration of a solution. - **Osmole** - Osmole: an expression of the concentration of a solution. - It is one gram molecular weight of osmotic active solute. - **EX:** one gram, molecular weight of glucose equals one osmo of glucose, which equals 180g of glucose. - Normal osmolality of extracellular and intracellular fluid is 300 milliosmoles per kg of water. - Osmolality does not exactly equal osmotic pressure, as there is an attraction between particles decreasing the net pressure. - **OsmolaRity (Requires Liters)** - Osmolarity is the osmole concentration per liter of solution. - Osmolarity is far more practical and there's only about a 1% difference, so it's used more frequently. - **Osmolality** - Osmolality is the osmole concentration per kilogram of solution. ## **Active Transport of Substances though membranes** - Some substances are required to have a large intracellular concentration, while others require a large extracellular concentration. - **Potassium has a large intracellular concentration of 140 Mk and a small extracellular concentration of 4 MQ.** - **Sodium has a large extracellular concentration of 142 Mk and a small intracellular concentration of 10 MQ.** - **Gradient** - In order to create these differences, active transport and the utilization of energy is required to move molecules or ions against a gradient. - This gradient can be created by: - Concentration - Pressure - Electrical charges - **Active Transport** - Divided according to the source of energy. - Active transport is dependent upon carrier proteins that penetrate through the membrane. - **EX:** The sodium potassium pump is responsible for maintaining the sodium and potassium concentration differences across the membrane, and establishing a negative electrical voltage inside the cell. - **Primary Active Transport** - Primary active transport is when the needed energy is derived directly from the breakdown of ATP or some other high energy phosphate compound.. - **Secondary Active Transport** - Secondary active transport is when the energy is derived secondarily from energy that has been stored as ionic concentration differences created originally by primary active transport. ## **Primary Active Transport** - **The Na+ K+ pump** - Maintains the concentration differences - **Contains:** - Three binding sites for sodium ions on the inside of the cell. - Two binding sites for potassium ions on the outside of the cell. - A site for ATP activity on the inside near the sodium binding site. - Maintains a negative electrical voltage INSIDE the cell by: - Three sodium ions bind to the inside of the cell. - Two potassium ions bind to the outside of the cell. - ATP is used to cause a conformation or change in the protein molecule, expelling the three sodium and forcing the two potassium ions inside the cell. - The pump can run in reverse if concentration gradients are needed to go the other way. - When the pump runs in reverse ATP is created from ADP. - The concentrations of ATP, sodium, and potassium determined the direction of the pump. ## **Controlling cell volume** - The sodium potassium pump is important for controlling cell volume.. - Without the functions of the pump most cells of the body would swell until they burst. - Intracellularly there are a large number of proteins and other organic molecules that cannot escape the cell. - These proteins are negative, each negatively charged. - They attract a large number of potassium, sodium, and other positively charged ions. - All these molecules and ions then cause osmosis of water inter-cellularly. - With Each Cycle of pump: - 3 Na ions are pumped out into ECF. - 2 K ions are pumped into the ICF. - There's a net loss of 1+ ion out of the cell. - This creates positivity outside the cell and intracellular negativity. - This is creates the electrical potential across the cell membrane. - It is required in nerve and muscle fibers for signaling. - If a cell begins to swell for any reason, the sodium potassium pump is activated to restore equilibrium. - **Calcium Ions** - Calcium is maintained in extremely low intracellular concentrations. - 2.4 MEQ outside versus 0.001 MEQ inside. - There are two primary active transport pumps for Ca. - ATP is utilized the same as a sodium potassium pump. - Only the binding site is specific for calcium instead. - Two primary active transport pumps - One pump moves calcium to the outside of the cell. - One active transport pump pumps calcium into the: - Sarcoplasmic reticulum of muscle cells. - Mitochondria of all cells. - The transport of calcium into the SR and the mitochondria are essential for muscle function. - **Hydrogen Ions** - The primary active transport of hydrogen is especially important in: - The parietal glands of the stomach - Secrete hydrochloric acid in the stomach for the acidic gastric secretions, causing digestion. - H+ ion concentration in stomach is increased, is increased as much as 1 million fold while renal tubular fluid. - The intercalated cells in the late distal tubules and cortical collecting ducts. - Secrete hydrogen from the blood into the renal tubular flow allowing for the elimination of excess hydrogen from the body in the stomach. - H+ ion concentration in the renal tubular fluid. Hydrogen ion concentration is as much as 900 fold. ## **Secondary Active Transport** - When sodium is transported out of the cell by primary active transport, a large sodium gradient is created across the cellular membrane. - A high Na+ concentration outside. - A low Na+ concentration inside. - This is stored energy (PE) - Just like pumping water into a water tower. - Due to this concentration gradient: - The sodium outside the cell is always attempting to diffuse to the interior. - Sodium can pull other substances along with it if it is allowed to diffuse. - This is secondary active transport. - **Co-Transport (symport)** - The carrier protein has an attachment for both the sodium ion and the substance to be Co transported. - Once they are both attached, the energy gradient of the sodium causes both substances to be transported together to the interior of the cell. - **Ex:** Na + Glucose - **Counter-Transport (antiport)** - Sodium moves down its concentration gradient utilizing the stored energy. - Other ions, such as calcium or hydrogen, moves in the other direction. - This is a mechanism for concentrating hydrogen ions. - Counter transport is not nearly as powerful as primary active transport. - **Ex:** Na/H counter-transport - Hydrogen is expelled into renal tubules where it is highly concentrated from the low concentration of the interstitial cell. - Glucose and amino acids are transported into most cells against a large concentration gradient entirely by Co transport. (symport) ## **Active Transport Through Cellular Sheets** - **Cellular Sheets** - In many places in the body, where substances must be trained is transported all the way through a cellular sheet instead of simply through a cell membrane. - Intestinal epithelium - Epithelium of renal tubules - Epithelium of all exocrine glands - Epithelium of the gallbladder - Choroid plexus of the brain. - This occurs through active transport, across the cell membrane on one side. - And simple diffusion or facilitate diffusion across the membrane on the opposite side of the cell. - The brush border on the luminal surfaces of the cell is permeable to Na+ ions and H20. - Causing sodium and water diffuse readily. - At the basal and lateral membrane sodium ions are actively transported into the extracellular fluid, creating a high sodium ion concentration gradient across the membranes. - This in turn causes the osmosis of water. - Active transport of sodium ions results in the transport of sodium ions, AND water. ## **1.4 Membrane Potentials (Guyton CH 5)** - https://youtu.be/rc6pwX8GpcY?si=KQv9iZZJGpFJ - https://youtu.be/Jk_9IhHVOTk?si=48qAOG-xACg