Lipscomb University College of Pharmacy Lecture 4 PDF

Membranes and Transport Lecture 4 PHSC 1212: Biomolecular Chemistry Lecturer: Rachel Crouch, Pharm.D., Ph.D.  Resources Reading Assignment: – McKee & McKee – Chapter 2 (pp. 37 and 45-48 ) and Chapter 11.2 – Martini & Nath – Chapter 3, Section...

Membranes and Transport Lecture 4 PHSC 1212: Biomolecular Chemistry Lecturer: Rachel Crouch, Pharm.D., Ph.D.  Resources Reading Assignment: – McKee & McKee – Chapter 2 (pp. 37 and 45-48 ) and Chapter 11.2 – Martini & Nath – Chapter 3, Section 3.1, 3.5 – 3.7  Lecture Objectives List the common attributes of biological membranes. Describe the functions of the plasma membrane. Describe membrane structure and the functions of the various membrane components. Describe the concept of selective permeability as it relates to cellular membrane transport (i.e. what characteristics determine whether a molecule can cross a cell membrane?).  Lecture Objectives Define the two major routes of transport across multicellular membranes. Define active and passive transport. Describe the various passive and active modes of transport across the plasma membrane.  Plasma Membrane Functions of the Plasma Membrane Physical isolation Barrier Regulates exchange with environment Ions and nutrients enter Wastes eliminated and cellular products released Monitors the environment Extracellular fluid composition Chemical signals (transmitted via cell surface receptors) Structural support Anchors cells and tissues  Common Attributes of Biological Membranes: 1. Thin, flexible sheet-like structures (two molecules thick) that form closed boundaries between different compartments (cells, organelles) 2. Consist mainly of lipids and proteins (also have carbohydrates) 3. Membrane lipids are small molecules that have hydrophilic and hydrophobic moieties (enables them to form closed sheets in aqueous media) Common Attributes of Biological Membranes: 4. Proteins mediate distinctive functions of membranes (e.g. pumps, channels, receptors, etc.) 5. Non-covalent assemblies 6. Asymmetric 7. Fluid structures 8. Most membranes are electrically polarized  Membrane structure Membranes are composed of: – Lipids (phospholipids, cholesterol) – Proteins (integral or peripheral) – Carbohydrates (typically tethered to proteins or lipids) T McKee and R McKee, Biochemistry: The Molecular Basis of Life ©2020 Oxford University Press  Membrane Lipids Two primary types: – Phospholipids have a polar head group and nonpolar tail group (form a bilayer with polar heads facing outward and tails inward) – Cholesterol increases membrane rigidity Lipid characteristics are responsible for: – Membrane fluidity – Selective permeability – Self-sealing capability – Asymmetry T McKee and R McKee, Biochemistry: The Molecular Basis of Life ©2020 Oxford University Press  Membrane Proteins Two types: – Integral membrane proteins – Peripheral membrane proteins Roles of membrane proteins: – Anchoring, recognition, enzymes, receptors, carriers, channels T McKee and R McKee, Biochemistry: The Molecular Basis of Life ©2020 Oxford University Press  Membrane Carbohydrates Three types: – Proteoglycans – Glycoproteins – Glycolipids Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings – Present outside the cell membrane and form a coating called the glycocalyx Glycocalyx serves several roles (lubrication/protection, anchoring/locomotion, recognition, binding specificity) EXTRACELLULAR FLUID Glycolipids Phospholipid Integral protein Integral of glycocalyx bilayer with channel glycoproteins Hydrophobic tails Plasma membrane Cholesterol Peripheral Hydrophilic proteins heads Gated channel Cytoskeleton CYTOPLASM (Microfilaments) Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Membrane Composition  Fluid Mosaic Model Current concept of membranes: A mosaic of protein molecules drifting laterally in a fluid bilayer of phospholipids T McKee and R McKee, Biochemistry: The Molecular Basis of Life ©2020 Oxford University Press  Membrane Fluidity Fluidity is determined by: Percentage of unsaturated fatty acids in phospholipids – More unsaturated chains = greater fluidity Composition and distribution of cholesterol in membrane – More cholesterol = less fluidity T McKee and R McKee, Biochemistry: The Molecular Basis of Life ©2020 Oxford University Press  Membrane Fluidity Rapid lateral movement of lipid molecules is responsible for the proper functioning of many membrane proteins Disrupted lipid bilayers can rapidly, spontaneously self-seal unless the break is very large Flipping of lipid molecules across the membrane is less common – Primarily occurs during membrane synthesis or when lipids become imbalanced – Requires enzymes flippase and floppase FIGURE 11.23 Lateral Diffusion in Biological Membranes T McKee and R McKee, Biochemistry: The Molecular Basis of Life ©2020 Oxford University Press  Membrane Permeability The plasma membrane is a barrier, but nutrients must get in and products and wastes must get out Cell and organelle membranes are selectively permeable – Allows some materials to move freely – Restricts other materials Selective permeability restricts materials based on – Size – Electrical charge – Molecular shape – Lipid/water solubility  Selective Permeability Small, nonpolar substances: high permeability – Nonpolar substances diffuse through the lipid bilayer down their concentration gradient Charged or polar substances: low permeability – Specific membrane proteins regulate the movement of ions and polar substances across the lipid bilayer (e.g., ion channels or carrier proteins)  Membrane Proteins Membrane proteins are classified by their specialized functions: – Anchoring proteins - Attach to structures inside or outside the cell – Recognition proteins - Label cells as normal or abnormal – Enzymes - Catalyze chemical reactions – Receptor proteins - Bind and respond to signal molecules (e.g., hormones) – Carrier proteins - Transport specific molecules through membrane – Channels - Regulate water flow and solutes through membrane  Integral and Peripheral Membrane Proteins Integral: embedded in and/or extending through Peripheral: bound to the surface of the membrane (inside or outside) FIGURE 11.26 Integral and Peripheral Membrane Proteins T McKee and R McKee, Biochemistry: The Molecular Basis of Life ©2020 Oxford University Press  Integral and Peripheral Membrane Proteins Integral example: integral – G-proteins coupled receptor – passes through the membrane 7 times Peripheral example: – G-protein – anchored to the cytosolic side of the membrane by insertion of a lipid tail peripheral  Lipid Rafts Although lipids and proteins can drift throughout the membrane (membrane fluidity), some proteins and lipids are confined to specific regions – Certain regions of the membrane contain combinations of lipids, cholesterol, and proteins that cluster together to form ordered platforms called lipid rafts – Cholesterol and sphingolipids are the “glue” holding a lipid raft together – Sphingolipids have saturated fatty acid tails – Lipid rafts facilitate interactions between certain membrane proteins and cell signaling molecules (by holding them in close proximity to one another)  Lipid Rafts sphingosine cholesterol Viruses 2010, 2, 1146-1180; doi:10.3390/v2051146  Membrane Carbohydrates Carbohydrates account for ~ 3% of the weight of a plasma membrane. Membrane carbohydrates are components of complex molecules such as: – Proteoglycans, glycoproteins, and glycolipids – Extend outside cell membrane – Form sticky “sugar coat” (glycocalyx) Functions of the glycocalyx – Lubrication and protection – Anchoring and locomotion – Specificity in binding (receptors) – Recognition (immune response) Figure 3–2 The Plasma Membrane. Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings  Transport Across Biological Barriers Multiple Biological Barriers exist to control passage of molecules into cells and between cells – Tissue Barriers – Cell Membrane Barriers Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings Pandit, Intro to Pharm. Sci.  Transport Across Biological Barriers 2 major transport routes of solutes across a multicellular membrane: – Transcellular: through cells (across cell membrane) – Paracellular: between cells (through cell junctions) Transcellular Paracellular  Types of Transcellular Transport Transcellular transport across a plasma membrane can be – Active (requiring energy and transporter proteins/complexes) – Passive (no energy required-driven by concentration gradients) Passive transport – Simple diffusion – Facilitated diffusion (channel or carrier mediated) – Osmosis (exclusive to water) Active transport (requires energy) – Carrier-mediated – Vesicular transport  Figure 3–22 Overview of Membrane Transport (Part 1 of 6). © 2018 Pearson Education, Inc. Simple and Channel-Mediated Diffusion © 2018 Pearson Education, Inc. Figure 3–15 Diffusion across the Plasma Membrane.  Figure 3–22 Overview of Membrane Transport (Part 3 of 6). © 2018 Pearson Education, Inc.  Figure 3–22 Overview of Membrane Transport (Part 2 of 6). © 2018 Pearson Education, Inc.  Figure 3–22 Overview of Membrane Transport (Part 4 of 6). © 2018 Pearson Education, Inc.  Figure 3–22 Overview of Membrane Transport (Part 5 of 6). © 2018 Pearson Education, Inc.  Figure 3–22 Overview of Membrane Transport (Part 6 of 6). © 2018 Pearson Education, Inc. © 2018 Pearson Education, Inc. Figure 3–22 Overview of Membrane Transport.