Intro to Biomembranes PDF

Lipids a) Glycerophospholipids Phosphates + Sphingosines phosphatidyl choline (PC) The movement of PS to the OUTER Sphingomyelins exoplasmic leaflet of plasma membrane signals apoptosis. p...

Lipids a) Glycerophospholipids Phosphates + Sphingosines phosphatidyl choline (PC) The movement of PS to the OUTER Sphingomyelins exoplasmic leaflet of plasma membrane signals apoptosis. phosphatidylserine (PS) * INNER phosphatidyl ethanolamine (PE) phosphatidylinositol (PI) * * The PI participates PE promotes curvature of membrane important in cell signalling for budding and fusion. X - serine, ethanolamine, choline, glycerol or inositol. Based on X, GP are named: phosphatidylserine (PS) phosphatidyl ethanolamine (PE) phosphatidylinositol (PI) phosphatidyl choline (PC) diphosphatidylglycerol (cardiolipin).  b) Sphingolipids Sphingomyelins are important component of nervous tissue in higher animals and are predominantly found in the myelin sheath of neurons. They are clinically important molecules as their deposition in brain leads to Niemann Pick disease which results in brain damage and early death. Glycosphingolipids: (as they are uncharged at pH 7) Cerebrosides (contain single sugar residues) -Galactosyl cerebrosides are generally found in Neutral glycolipids M..............................neural membranes -Glucosyl cerebrosides are present in M,,,membranes of non neural tissues. Globosides (contain two or more sugar residues) Glycosphingolipids are largely found at the outer surface of plasma membrane where they act as recognition sites. Gangliosides: Presence of sialic acid gives gangliosides negative charge at pH 7 that distinguishes them from neutral glycolipids. c) Galactolipids and sulfolipids Galactolipids are present in thylakoid membranes of chloroplasts and make up 70-80% of the total membrane lipids in vascular plants. Thus, galactolipids are probably the most abundant membrane lipids in biosphere. Sulfolipids contain a sulfonated glucose residue attached to diacylglycerol by a glycosidic linkage. The sulfonate group carries negative charge d) Sterols Sterols: Cholestrol  Proteins Functional class Location on of membrane Examples membrane protein GLUT, Na+/K+ ATPase, Transporters Transmembrane Transmembrane K+ channel Insulin receptor, rhodopsin, Receptors Transmembrane adrenergic receptor G protein, phospholipases, Transmembrane Enzymes Cytochrome P450 or Surface Cell adhesion molecules such as Transmembrane Structural cadherins or Surface Non constit- Ionophores such as gramicidin, Transmembrane utive cholera toxin Transmembrane proteins are always intrinsic proteins while surface bound proteins may be of intrinsic or extrinsic type.  Types of membrane spanning domains: Bacteriorhodopsin, the light driven proton pump found in Halobacterium salinarum, has seven transmembrane Outer membrane alpha helices. This motif of Gram Negative was observed for the first Bacteria time in this protein. * ** Example for Alpha-beta type transmembrane Ca2+-ATPase pump in sarcoplasmic reticulum ** * Alpha-beta type (alpha type proteins have extramembranous domains either on one or both the sides of the membrane) [I] Alpha Type (Alpha Helix Proteins): Made of alpha helices that go through the membrane. 1. Bitopic proteins: These proteins have just one alpha helix spanning the membrane, connecting the two outside parts of the protein. 2. Polytopic proteins: These proteins have multiple alpha helices (more than one) that go back and forth through the membrane multiple times. channels in the cell membrane have Example: Na+ (sodium) the highest number of alpha helices. Ca2+ (calcium) [II] Beta Type (Beta Strand Proteins): Made of beta strands that form a barrel-like structure. These beta strands align in an antiparallel fashion and form a cylindrical structure called a beta barrel. [III]Alpha-Beta Type (Mixed Structure Proteins): Many proteins are a mix of alpha helices and beta strands. These proteins usually have extramembranous domains (parts of the protein that are outside the membrane) on one or both sides of the membrane. Example: Ca2+-ATPase pump in the sarcoplasmic reticulum (a structure in muscle cells) is an example of an alpha-beta type protein.  Glycocalyx Oligosaccharide Glycoproteins Glycolipid Integral Hydrophobic proteins α helix Cholesterol Peripheral Intrinsic surface bound proteins protein Strong lipid Bond (Covalent-Bond) Phospholipid Extrinsic surface bound proteins Weak lipid Bond (H-Bond) Membrane Major protein Glycophorin, Spectrin, Human RBC Glyceraldehydes-3 dehydrogenase Human myelin Basic protein; Lipophilin *Rabbit sarcoplasmic reticulum Ca2+ ATPase ** Purple membrane Bacteriorhodopsin Halobacterium halobium * α-β helix Protein ** α helix Protein  FLUID MOSAIC MODEL (a) Lipid nature of membranes Overton's Observation (1890s): Rate of small (d) Transemembrane Proteins molecule penetration through plant membranes linked to partition Lenard and Singer (1960s): coefficient between oil Proposed model including and water. transmembrane proteins for membrane transport and (b) Lipid Bilayer receptors. Gorter and Grendel (1925): Proposed lipid bilayer based on erythrocyte membrane studies. (e) Fluid Mosaic Model (c) Unit Membrane Model S.J. Singer and G.L. Nicolson (1972): Proposed Fluid Mosaic Model. Davson and Danielli (1935): Lipoid phase Explains membrane coated by proteins on both sides. structure and protein Supported by X-ray diffraction and dynamics. electron microscopy.  MEMBRANE MODEL SYSTEMS Monolayer (Consists of a thin layer of (Barrier adjusts Purpose and Function: water and a movable the area of the monolayer) Determines surface density (how closely molecules barrier) are packed) Measures lateral pressure needed to maintain monolayer stability Helps study behavior of surface-active lipids Useful for understanding properties of enzymes like lipases (which break down fats) Langmuir Trough (Device used to create and study monolayers) Bilayer These mimic the lipid bilayer structure of biomembranes. Electrical measurements made on this system give useful information about ion channels or pores or carriers which are present in the membrane.  Large unilamellar vesicles (LUV) Liposomes used for: transport experiments Small unilamellar vesicles (SUV) fusion experiments drug delivery vehicles (prepared by sonication and Multilamellar vesicles (MLV) are homogeneous in nature, (made up of multiple ∴useful to study properties.) concentric bilayers.) Lyotropic Crystals These crystals give information about the structure and arrangement of lipids as well as their dynamics in membranes and lipid protein interactions. Extras PageNo.4