Cell Membrane PDF

Cell membrane Máté Mackei Prokaryotes and Eukaryotes  Prokaryotes and eukaryotes Cells without a nucleus = Prokaryotes includes the bacteria generally very small, unicellular the earliest and still most abundant life forms; evolved ~ 4 billion years ago some spec...

Cell membrane Máté Mackei Prokaryotes and Eukaryotes  Prokaryotes and eukaryotes Cells without a nucleus = Prokaryotes includes the bacteria generally very small, unicellular the earliest and still most abundant life forms; evolved ~ 4 billion years ago some species highly evolved pathogens Cells with a nucleus = Eukaryotes include animals, plants, fungi some unicellular, some multicellular forms evolved ~ 1 billion years ago size ranges are different  Eukaryotic cell with cell membrane and subcellular membranes (thickness: 6-10nm) Plasma membrane: barrier between cell and environment Internal membranes: separate subcellular organelles from the cytoplasm  Cell (biological) membrane There are three major groups of components Lipids/lipoids (40%) Proteins (60%) Carbohydrates (less than 1%) Lipid bilayer provides the basic structure. They are partly simple lipids - (triacylglycerols) or mostly composed lipids (mainly phospholipids: sphingomyelin, lecithin, cephalin) and cholesterol with steroid structure intercalates between lipid molecules (only in eukaryotes!) Proteins are integrated into the lipid bilayer or found on the surface of the membrane. Sugar moieties can be present as part of either proteins (glycoproteins) or lipids (glycolipids). Constituents of the membrane: Lipids →Phospholipids → Glycerolphosphatides Phospholipids: major components of the cell membrane If the phospholipids have a glycerol backbone is called as Glycerolphosphatide They are similar to fats, but have only two fatty acids rather than three. The third hydroxyl group of glycerol is joined to a phosphate group, which is negative in electrical charge. Additional small molecules, usually charged or polar (choline or cholamine in lecithin and cephalin), can be linked to the phosphate group to form a variety of phospholipids.  Lipids →Phospholipids → Glycerolphosphatides Hydrophobic tail: non-polar fatty acids Hydrophilic head: polar molecules (glycerol, phosphate, choline, cholamine, etc) glycerol phosphate polar fA non polar  Lipids →Phospholipids → Glycerolphosphatides → Structure of lecithin; cephalin and phosphatidic acid Choline=trimethyl -ethanolamine Cholamine= ethanolamine Phosphate=P Fatty acid=FA 17 If instead of choline there is a cholamine in the molecule: cephalin=glycerol + 2FAs + P + cholamine The backbone with neither choline nor cholamine = phosphatidic acid=glycerol+2FAs+P Phosphatidic acid (Ø) Phosphatidil-serine (+Ser) Cephalin (+cholamine/ethanolamine) Lecithin (+choline/trimethyl-ethanolamine) Phosphatidil-inositol (+inositol) Lipids →Phospholipids → Sphingolipids Sphingosine: 18-carbon amino alcohol with an unsaturated hydrocarbon chain, Sphingosine+fatty acid (amide bond) → Ceramide (if no other group is connected) Ceramide + phosphate + choline (ester bond) → Sphingomyelin X  Substituent (R) Sphingolipid name Ø (-H) Ceramides Choline (+Phosphate!) Sphingomyelins Single sugar part Cerebrosides (monosaccharides) Oligosaccharides Gangliosides Hydrophobic tail: non-polar fatty acids and hydrocarbon chain of sphingosine Hydrophilic head: polar molecules (phosphate, choline) Saturated and unsaturated fatty acids in the lipids Nupha  Saturated and unsaturated cis-fatty acids Unsaturated fatty acid: generally 1-3 double bonds at defined locations along the hydrocarbon chain. The fatty acid will have a kink in its shape wherever a cis-double bond occurs that results in looser packing and lower melting points. This feature plays an important role in the relationship between temperature and the fluidity of the cell membrane. University of New Hampshire  Lipids →Cholesterol Steroid molecules include cholesterol and certain hormones Characterized by a carbon skeleton consisting of four fused rings Cholesterol, is a common component of animal cell membranes: providing stability Precursor from which other steroids are synthesized Thus cholesterol is a crucial molecule in animals although high levels of it in the blood may contribute to atherosclerosis, because by restraining the movement of phospholipids decreases the fluidity of the membrane!! It can not be found in prokaryotes! Lipids →Cholesterol Interspersed among phospholipid tails in the bilayer Cholesterol is a steroid lipid: carbon skeleton consisting of four fused rings. Hydrophobic: ring structure, except –OH group Hydrophilic head: –OH group at C-3 LDL bound cholesterol has a role in the plaque formation in blood vessels Narrowing of arteries by cholesterol plaques! Movement of lipids in the membrane Rotation Lateral Diffusion Transversal Diffusion („flip-flop”) Flippase or floppase protein is needed (+energy demand: ATP) Scambalase (no ATP!) ATP  Lipid rafts Spingolipid and cholesterol rich microdomain -Find – ordered assemblies of specific proteins = lipid raft, More ordered and more stable areas – cholesterol holds together the lipid and protein constituents, Important role in the cellular machinery – membrane transport – fluidity – signal transduction – neurotransmission Constituents of the membrane: Proteins About 60% of the membrane The most structurally sophisticated molecules More than 50% of the dry weight of most cells Animals have tens of thousands of different proteins, each with a specific structure and function Polymers constructed from the same set of 20 amino acids Membrane proteins are classified into two (three) major categories: Integral proteins Peripheral proteins  Integral and peripheral proteins Integral proteins: Generally transmembrane proteins, with hydrophobic regions that completely span the hydrophobic interior of the membrane. The hydrophilic ends of the molecule are exposed to the aqueous solutions on either side of the membrane. Proteins are much larger than lipids and move more slowly, but some do drift. Some membrane proteins seem to move in a highly directed manner, however, many others seem to be held virtually immobile by their attachment to the cytoskeleton. They have dynamic function, they serve generally as ion channels. Integral and peripheral proteins Peripheral proteins Not embedded in the lipid bilayer at all Loosely bound to the surface of the membrane, or to parts of integral proteins Static function, often receptors Constituents of the membrane: Carbohydrates Usually branched oligosaccharides with fewer than 15 sugar units (glucose, galactose, mannose, etc.) Some of them are covalently bonded to lipids, forming molecules called glycolipids. Most are covalently bonded to proteins, which are called glycoproteins. The oligosaccharides on the external side of the plasma membrane vary from species to species, among individuals of the same species, and even from one cell type to another in a single individual. The diversity of the molecules and their location on the cell’s surface enable oligosaccharides to function as markers that distinguish one cell from another. Function: Detection of foreign cells by the immune system Binding of biologically active molecules (such as plant lectins) Colonization of bacteria on the cell surface Cell-cell interactions: metastases of tumors Constituents of the membrane: Carbohydrates The most important monosaccharide components of the membrane: Glucose N-acetyl-glucose-2-amine Mannose N-acetyl-mannose-2-amine Mannose-2-amine+pyruvate= =neuraminic acid (C9) Galactose N-acetyl-galactose-2-amine Fucose (6-deoxy-galactose) S. J. Singer Membrane-fluidity (fluid-mosaic model) Singer-Nicholson (1972) Membrane fluidity and rigidity depends on different factors (fluidity elasticity rigidity) Membrane fluidity (elasticity) increases: Increased temperature Decreased amount of cholesterol (cholesterol can be found only in eukaryotes!) Increased proportion of cis-unsaturated fatty acids in the phospholipids Each membrane constituents (lipids, proteins, carbohydrates) are continuously moving!  Importance and function of the biological membrane Cell membranes (plasma membrane, subcellular membranes) are selective barriers → selective transport systems are needed to regulate the flow of molecules and ions across membrane (transport function) But: Cell membranes are not only barriers They control the structures and environments of the compartments, they define thereby the metabolism of these compartments The membrane itself is a metabolic compartment with unique functions Membranes are dynamic They can move Their components are continuously synthesized and degraded The primary event in cell death (e.g. myocardial infarction): may be damage to the cell membrane, leading ultimately to cell death Membranes are asymmetric  Assymetry Membranes have distinct inside and outside faces Cell membranes are made up of two lipid monolayers The two lipid layers may differ in specific lipid composition, and each protein has directional orientation in the membrane The plasma membrane also has carbohydrates, which are restricted to the exterior surface This unequal distribution of molecules between both monolayers is referred as membrane asymmetry, and was known even before the fluid mosaic model of membrane was proposed in 1972. One characteristic example: lipid rafts