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BIOL 1F90 Study Guide Chapter 6.docx

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Brock University
Douglas Bruce

BIOL 1F90 Study Guide: Chapter 6 Introduction  Cellular membranes, also known as biological membranes or biomembranes, are an essential characteristic of all loving cells  Plasma membrane: Separates the internal contents of a cell from its external environment o Primary function is membrane transport  Cellular membranes are thin, typically 5-10nm thick and somewhat fluid  Biomembranes regulate the traffic of substances into and out the cells and its organelles Table 6.1: Important functions of Cellular Membranes Function Selective uptake and export of ions and molecules Cell compartmentalization Protein sorting Anchoring of the cytoskeleton Production of energy intermediates, such as ATP and NADPH Cell signaling Cell and nuclear division Adhesion of cells to one another and to the extracellular matrix Biological Membranes are a mosaic of Lipids, Proteins and Carbohydrates  All biological membranes consist if two layers of lipids, with the most abundant lipids being phospholipids  Amphipathic molecules: they have a hydrophobic (water fearing) region and a hydrophilic (water loving) region o The hydrophobic tails of the lipids, referred to the fatty acyl tails, form the interior of the membrane and the hydrophilic head groups are on both exterior surfaces o A phospholipid bilayer, with its hydrophobic interior, makes it difficult for hydrophilic molecules to move across the membrane, thus providing the fundamental ability of biological membranes to form compartments  Cellular membranes always contain protein o most also have carbohydrates attached to lipids and proteins  Fluid Mosaic Model: Membrane is considered a mosaic of lipid, protein and carbohydrate molecules o The membrane exhibits properties the resemble a fluid because lipids and proteins can move laterally relative to each other within the membrane  Leaflet: Half of a phospholipid bilayer Membranes are semifluid  Biomembranes exhibits properties of fluidity, which means that individual molecules remain in close association yet have the ability to readily move within the membrane  In a fluid substance, molecules can move in three dimensions  Most lipids can move freely in only two dimensions o 1. Around their long axes o 2. Laterally within the membrane leaflet  Cells have three types of proteins embedded in membranes that can accomplish these transfers o 1. Scramblase: provide a protein passageway for lipids to move across the bilayer  Scramblases transfer phospholipids along a concentration gradient, from the leaflet with a higher concentration to the leaflet with a lower concentration of that lipid  The transfer foes not require ATP o 2. Flippases: move lipids from the outer leaflet to the inner one o 3. Floppases: move lipids from the inner leaflet to the outer one  Flippases and floppases both require the energy acquired from hydrolysis of ATP to accomplish their directed flipping  The biochemical properties of sterols and phospholipid bilayer o 1. The length of their fatty acyl tails; shorter acyl tails are less likely to interact, which makes the membrane more fluid o 2. The presence of double bonds in the acyl tails; When a double bond is found, the lipid is said to be unsaturated with respect to the number of hydrogens that can be bound to the carbon atoms. A double bond creates a kink in the fatty acyl tail, making it more difficult for neighboring tails to interact and consequently making the bilayer more fluid o 3. The presence of sterols interspersed throughout the membrane, particularly the plasma membrane  Optimal level of bilayer fluidity is essential for normal cell function, growth, and division  Lipid rafts: Regions of distinctive phospholipids enriched in sterols and membrane proteins o tend to have fatty acyl tails that are straight and hence can pack more tightly together o They are thus more stable and tend to stay clustered as a unit (raft) o The name derives from the fact that the phospholipid, sterols, and proteins remain associated with each other and float together in the semifluid membrane o Lipid rafts often are regions in which specific membrane proteins are inserted, specially those involved cell signaling Membrane Proteins  The protein component carries out most other functions. Proteins can bind to membranes in three different ways o 1. Transmembrane Protein: span the bilayer, having one or more regions that are physically embedded in the hydrophobic region of the phospholipid bilayer  The transmembrane segments are folded into a alpha helical regions stabilized by hydrogen bonds.  These segments are stable in the membrane interior because the nonpolar amino acids interact favorably with the hydrophobic fatty acyl tails of the lipids o 2. Lipid anchors: A lipid anchor involves the covalent attachment of a lipid to an amino acid side chain within a protein  This attachment is done post- transnationally after the polypeptide is created  The fatty acyl tails of the lipid anchor keep the protein firmly bound in the membrane leaflet in which it is embedded  Both transmembrane proteins and lipid anchored proteins are classified as integral membrane proteins, also called intrinsic membrane proteins because they can’t be released from the membrane unless the membranes are dissolved with an organic solvent or detergent  In other words, you would have to disrupt the integrity of the membrane to remove them o 3. Peripheral membrane Proteins: Also called extrinsic proteins, are a third class of membrane proteins  These proteins do not interact with the hydrophobic interior of the phospholipid bilayer.  They are non covalently bound to regions of integral membrane proteins that project out from the membrane, or they are bound to the polar head groups of phospholipids  Typically bound to the membrane by hydrogen or ionic bonds. For this reason, they usually can be removed from the membrane experimentally by exposing the membrane to high salt concentrations Genomes and Proteomes  Membrane proteins participate in many important cellular processes. These include transport, energy transduction, cell signaling, secretion, cell recognition, and cell to cell contract  A gene encodes a protein that is a membrane protein  Estimated percentage of membrane proteins is substantial o 20%-30% of all genes may encode membrane proteins Evolution and Adaptation of membranes and membrane constituents  Diversity of eukaryotic membrane function is reflected in the large number of different membrane proteins encoded by eukaryotic genomes  Eukaryotes make special lipids know as cerebrosides that give membrane special properties  Some plants make specific glucosyleramides that elicit defense responses against fungal attack Glycosylation of Lipids and Proteins serves a Variety of Cellular Functions  Glycosylation: The process of covalently attaching a carbohydrate to a protein or lipid.  Glycolipid: created when a carbohydrate of biomembranes is attached to a lipid  Glycoprotein: Produced when a carbohydrate of biomembranes attaches to a protein  Cell Coat/glycocalyx: Carbohydrate rich zone on the cell surface that shields the cell from mechanical and physical damage  The carbohydrates that are attached to proteins and lipids have well defined structures that serve in some cases as recognition signals for other cellular proteins  Similarly, membrane glycolipids and glycoproteins often play a role in cell surface recognition. Experiments on lateral diffusion  Larry Frye and Michael Edidin conducted an experiment that verified the lateral movement of membrane proteins  Mouse and human cells were fused o Temp treatment 0 or 37 o Mouse membrane protein H-2 fluorescently labeled  0 cells- label stays on mouse side  37 cells- label moves over entire cell Not all integral membrane proteins move  depending on the cell type, 10%-70% of membrane proteins may be restricted in their movement  integral membrane proteins may be bound to components of the cytoskeleton, which restricts the proteins from moving laterally  Also, membrane proteins may be attached to molecules that are outside the cell, such as the interconnected network of proteins that forms the extracellular matrix Membrane structure can be viewed with electron microscope  Electron microscopy is a valuable tool for probing membrane structure and function.  In transmission electron microscopy (TEM), a biological sample is sectioned and stained with heavy metal dyes, such as osmium tetroixide  A specialized form of electron microscopy, freeze fracture electron microscopy (FFEM), can be used to analyze the architecture of biological membranes, most often the plasma membrane  In FFEM, a sample is frozen in liquid nitrogen and split open with a knife  The knife fractures the frozen sample because of the weakness of the hydrophobic fatty acyl tails, the leaflets separate into a P layer ( the leaflet in contact with the cytosol) and the E face ( the leaflet of the cell membrane in contact with the extracellular matrix)  Unlike the lipid bilayer, most transmembrane proteins do not break in haf.  They remain embedded within one of the leaflets, usually in the P layer. Integral membrane proteins that don’t span the membrane stay embedded in their original leaflet Membrane Transport  Selectively permeable plasma membrane  Structure ensures… o Essential molecules enter o Metabolic intermediates remain o Waste products exit Phospholipid Bilayer is a Barrier to Diffusion of hydrophilic Molecules  Phospholipid bilayers present a formidable barrier to the movement of ions and hydrophilic molecules  Diffusion: Occurs when a solute ( ie a dissolved substance) moves from a region of high concentration to a region of lower concentration  Passive Diffusion: Diffusion occurring through a membrane without the aid of a transport protein Diffusion through bilayer  The rate of passive diffusion depends on the chemical properties of the solute and its concentration  Gases and a few small uncharged polar molecules can passively diffuse across the bilayer.  However, the rate of diffusion of ions and larger polar molecules, such as sugars and amino acids, is relatively slow  Similarly, macromolecules, such as proteins and large carbohydrates, do not readily cross a lipid bilayer.  For relatively small molecules their hydrophobicity is a key determinant of how readily they can diffuse across a phospholipid bilayer Ways to move across the membrane  Passive transport: does not require an input of energy—down or with gradient  Passive transport mechanisms tend to dissipate a pre existing gradient o Passive diffusion: diffusion of a solute through a membrane without transport protein o Facilitated diffusion: Diffusion of a solute through a membrane with the aid of a transport protein  Active Transport: Requires energy—up or against gradient Transmembrane Gradient: The concentration of a chemical (solute) is higher on one side of a membrane than the other  Living cells maintain a relatively constant internal environment different from their external environment  Ion chemical gradient: both an elec
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