Download as PDF, PPTX
Cell Membrane Composition and Function_240417_114329.pdf
- 1. Cell Membrane Alissa LaurelN. Calderon, MD, FPAFP, MMHA
- 2. Cell • Fundamental unitof life • Cells make up all living matter • All cells arise from other cells • The chemical reactions of an organism , both anabolism and catabolism, takes place in the cell
- 3.
- 4.
- 5. Nucleus • Contains morethan 95% of the cell’s DNA • Control center of the cell • Where DNA replication and RNA transcription of DNA occur
- 6. Parts of aNucleus • Nuclear envelope – double membrane structure that separates the nucleus from the cytoplasm • Nuclear pore complexes – these are embedded in the nuclear envelope; control the movement of proteins and RNAs across the nuclear envelope • Nucleoplasm – contains various enzymes such as DNA polymerases and RNA polymerases for mRNA and tRNA synthesis
- 7. Parts of aNucleus • Chromatin – made up of coiled DNA; stained darkly with certain dyes • Nucleolus – second dense mass closely associated with the inner nuclear envelope – Nonmembranous; contains RNA polymerase, ATPase, but no DNA polymerase – Site of synthesis of ribosomal RNA (rRNA) – Major site where ribosome subunits are assembled
- 8. Mitochondria • Powerhouse ofthe cell • Bounded by two concentric membranes that have different properties and biological functions
- 9. Mitochondrial Membrane • Outermitochondrial membrane – consists mostly of phospholipids and cholesterol; also contains protein porin – Porin – proteins that form channels that permits substances with MW <10,000 to diffuse freely across the mitochondrial membrane
- 10. Mitochondrial Membrane • Innermitochondrial membrane – Very rich in proteins – Contains high proportion of the phospholipids cardiolipin – Impermeable to polar and ionic substances (as opposed to outer membrane) – Cristae – inner mitochondrial membrane is highly folded; tightly packed inward folds are called cristae
- 11. • Mitochondrial matrix– region enclosed by the inner membrane – Where enzymes responsible for citric acid cycle and fatty acid oxidation are located
- 13. Endoplasmic Reticulum • Extendsfrom the cell membrane, coats the nucleus, surrounds the mitochondria and appears to connect directly to the Golgi apparatus
- 14. Kinds of ER •Rough ER – coated with ribosomes; near the nucleus, it merges with outer membrane of the nuclear envelope; synthesizes membrane lipids and secretory proteins • Smooth ER – do not have attached ribosomes; responsible with lipid synthesis, and modifies and transports proteins synthesized by RER
- 15. Golgi Apparatus • Uniquestack of smooth surfaced compartments or cisterna • It is usually closely associated with ER • Has proximal or cis compartment, a medial compartment and a distal or trans compartment • Serves as a unique sorting device that receives newly synthesized proteins, all containing signal or transit peptides from the ER – Those proteins with no signal or transit peptides regions are rejected by the golgi apparatus without processing further – Remains as cytoplasmic protein
- 16. Functions • Proximal orcis side – receives the newly synthesized proteins by the ER via transfer vesicles • Median part – where posttranslational modification take place – Where the carbohydrates and lipid precursors are added to proteins to form glycoprotein and lipoproteins respectively • Distal or trans side – release proteins via modified membranes called secretory vesicles
- 17. Lysosomes • Contains packetof enzymes • Found in all cells, except RBC • pH inside is lower than that of the cytoplasm – Lysosomal enzymes have an optimal pH of 5 – Acid phosphatase is used as a marker enzyme – Enzymes are hydrolytic in nature
- 19. Peroxisomes • Small organelles,approximately 0.5μ in diameter • They have no energy-coupled electron transport systems – Formed by budding from SER
- 20. Functions • They carryoutoxidation reactions in which toxic hydrogen peroxide (H2O2) is produced, which is destroyed by the enzyme catalase. • Liver peroxisomes have an unusually active β- oxidative system capable of oxidizing long chain fatty acids (C 16 to 18 or > C 18) – β-oxidation enzymes of peroxisomes are rather unique in that the first step of the oxidation is catalyzed by a flavoprotein, an “acyl Co-A oxidase” – H2O2 produced is destroyed by catalase.
- 21. Biological Membrane system •Highly dynamic two layers thick sheath like structures formed by lipids, proteins and carbohydrates • Serves as closed boundaries between different compartments of the cells • Nuclear membrane: nucleoplasm from cytoplasm • Act as barriers to the passage of polar molecules and ions
- 22. Cell Membrane • Existsin viscous—gel-fluid like—and plastic structures (ex. RBCs). • Dynamic—exhibits rapid turnover and lateral diffusion • Has a thermodynamically stable and metabolically active arrangement • Composed of lipids, proteins and carbohydrates
- 23. Functions of CellMembrane • Selective barrier – aided by carriers and channels, allowing exchange between the cell and the environment • Permits cell individuality – separates cell from other cells • Cell-to-cell interaction – due to hormone- receptor interactions • Cell adhesion to basement membrane and other cells
- 24. Functions of CellMembrane • Transmembrane signaling – signal transduction mechanism • Compartmentalization • Localize enzymes • Excitation-response coupling • Site for energy transduction
- 25. Cell Membrane • Asymmetric,sheet-like structure with an inner leaflet (exposed to the ICF) and an outer one (exposed to the ECF) – Structure is due to noncovalent assemblies that form spontaneously in water due to the amphipathic nature of lipids • Two sides of the membrane are not structurally and functionally identical – The difference in composition of lipids and proteins – Difference in positioning and orientation of the membrane proteins – Difference in the enzymatic activities of the inner and outer surfaces
- 26. Cell Membrane Asymmetry •“Inside-Outside” Asymmetry – Due to irregular distribution of proteins – Carbohydrates are only found externally – Specific locations of enzymes • Ex. In the mitochondria, enzymes involved in ETC are found on the inner mitochondrial membrane) – Nature of phospholipids • outer leaflet: phosphaditylcholine, sphingomyelin, glycolipids • Inner leaflet: phosphatidyiethanolamine, phosphatidylserine, phosphatidylinositol • “Regional Asymmetry” – Villous borders, gap junctions, tight junctions – Found in specific sites
- 28. Significance • Changes inphospholipid asymmetry is involved in various cell functions: cell polarity, membrane trafficking and organelle functions • Phospholipid asymmetry is generated, maintained and regulated by lipid translocation or “flip-flop”
- 29.
- 30. • Composed oflipids, proteins and carbohydrates – 40% - lipids – 60% - proteins – 1-10% - carbohydrates • All membrane carbohydrate is covalently attached to proteins or lipids
- 32. A. Lipids • Providebasic structure; backbone • Amphipathic due to hydrophobic (non polar) tail and hydrophilic (polar) head – attributing to formation of a bilayer • With FA tails – Saturated FAs – straight tails à organized, compact, crystalline membrane – Unsaturated FAs – kinked tails à due to double bond, disorganized, fluid membrane
- 33. Lipid Bilayer • Hydrophilicand hydrophobic interactions are responsible for the bilayer organization of membranes in the cells
- 34. Classification of MembraneLipids Membrane Lipids Phospholipids glycolipid sterols Glycero-phospholipids Sphingo-phopholipids Galactolipids Sphingo-glycolipids
- 35. 1. Phospholipids • Glycerol-3-phosphate(phosphoglycerides) – backbone of all phospholipids • Polar “head” group is joined to the hydroxyl (OH-) group of the C3 of a glycerol by phosphodiester linkage • The other OH- groups (C1 and C2) of the glycerol is sterified by fatty acids
- 36.
- 37. Phospholipids lipids with phosphate groups.Lends to selective permeability of cell membrane as it allows lipophilic substances (O2, CO2, alcohol) to pass through
- 38. Sub-Categories of Phospholipid • Phosphoglycerides(Glycero-phospholipids) – most common phospholipid – consist of a glycerol backbone + 2 fatty acid chains connected via ester linkages + phosphorylated alcohol – (e.g. ethanolamine, choline, serine, glycerol, or inositol) – Fatty acids are even-numbered (16-18 C atoms) which could be saturated or unsaturated – Simplest form is phosphatidic acid
- 39. Fatty acid glycerolAlcohol
- 40. Name of X- OH Formula of -X Phospholipid Name Water - H Phosphatidic acid Ethanolamine -CH2CH2NH3 Phosphatidylethanolamine Choline -CH2Ch2N(CH3)3+ Phosphatidylcholine (Lecitin) Serine -CH2CH(NH3+)COO- Phosphatidylserine Glycerol -CH2CH(OH)CH2OH Phosphatidylglycerol Phosphatidylglyceroll Diphosphatidylglycerol (Cardiolipin) Myoinositol Phosphatidylinositol
- 41. Cardiolipin • Complex glycero-phospholipid •polar head (-X) is a phosphatidylglycerol thus structurally, a diphosphatidylglycerol • An important component of the inner mitochondrial membrane – constitutes about 20% • Lipid marker of the inner mitochondrial membrane (not found in outer mitochondrial membrane)
- 42.
- 43. Plasmalogen • C1 ofglycerol moiety is linked to fatty acid via an α,β-unsaturated ether linkage rather than an ester linkage • Present in abundance in neurons and cells of cardiovascular system
- 44.
- 45. Sphingo-phospholipids (Sphingolipids) • Second subcategory of phospholipids • A C18 amino alcohol called sphingosine backbone instead of glycerol backbone • The N-acyl fatty acid derivative of sphingosine at C2 is called Ceramide
- 46.
- 47. • Sphingomyelin – Mostcommon sphingo-phospholipids – contains a sphingosine backbone instead of glycerol – A fatty acid is attached by an amide link to the amino group of sphingosine = CERAMIDE – Hydroxyl group of sphingosine is esterified to phosphorylcholine – Sphingomyelin is prominent in myelin sheath
- 48.
- 49. 2. Glycolipids • Polarhead group holds one or more carbohydrate moieties and its derivatives. • Lipids conjugated with carbohydrates have other 2 important functions, besides in the membrane: • Provide energy • Acts as markers for cellular recognition
- 50. Classification of Glycolipids •2 sub-categories a. Glyceroglycolipids – glycerol backbone with carbohydrates - Galactolipids - sulfolipids b. Sphingoglycolipids – sphingosine backbone with carbohydrate - Cerebrosides - Gangliosides - Globosides
- 51. Glyceroglycolipids • have glycerolbackbone with carbohydrate heads • 2 important glyceroglycolipids: – Galactolipids – Glyceroglycolipids
- 52. Galactolipids • The C3of the glycerol moiety is connected to one or more galactose residues by glycosidic residues • The C1 and C2 of glycerol are esterified with fatty acids • Predominantly present in plant cells particularly the thylakoid membranes of chloroplasts
- 53. Sulfolipids • Membrane glycolipidswith sulfur containing functional groups • Sulfonated glucose is joined to the C3 of diacylglycerol in glycosidic linkage
- 54. Sphingoglycolipids • sugar attachedto ceramide backbone rather than glycerol moieties • found in nerve tissue a. Cerebrosides b. Gangliosides c. Globosides
- 55. Cerebrosides • A ceramidewith single sugar residue at the C1-hydroxyl group • Sugar residue is either glucose or galactose • Lack the phosphate group thus they are non-ionic (no charge) • Abundant in cell membranes of nerves and muscles of animals – Nerve cells – rich in galactocerebrosides
- 56.
- 57. Gangliosides • Membrane lipidwith most complex structure • It is a glyco-sphingolipid with many carbohydrate moieties and one or more sialic acids linked on the sugar chain • About 6% of brain lipids are gangliosides and they are first isolated from the ganglion of brain cells – Also abundant in the lipid rafts of plasma membrane
- 58.
- 59. Globosides • With oneor more than one sugar as the side chain of a ceramide • Differ from gangliosides since they lack the sialic acid residues • The carbohydrate moieties are usually a combination of N-acetyl-galactosamine,D- glucose or D-galactose
- 60.
- 61. 3. Sterols • Thirdmajor category of membrane lipids, usually present in eukaryotoc membranes • Structurally consist of four fused carbon rings (A, B, C, D) and a hydrooarbon chain (alkyl side chain) • Rings A, B, C are 6-carbon rings; D is 5-C structure • This fused ring structure is called the steroid nucleus • Cyclopentanoperhydrophenanthrene • One of its peculiarities of carbon in fused ring structure – does not allow C-C free rotation even though they are in single bonds
- 62.
- 63. Cholesterol • Most commonsterol and intercalates with membrane phospholipids • 27-C atom with 4-rings conferring rigidity • Amphipathic with single polar hydroxyl (-OH) ‘head’ and non-polar hydrocarbon ‘tail’ • The –OH group and hydrocarbon chain are attached to the C3 and C17 of steroid nucleus • Can esterify long chain fatty acids to to form cholesterol esters such as cholesteryl stearate
- 65. • “moderator molecule”moderates membrane fluidity Tm – transition temperature; temperature at which cell membrane become disorganized;structure undergoes from ordered to disordered state
- 66. B. Proteins • Amphipathicstructures • Determines membrane function • Act as pumps, channels, carriers, receptors, enzymes, structural components, antigens
- 67. MEMBRANE PROTEIN Membrane proteinshave various functions: 1. Transporters 2. Enzymes 3. Cell surface receptors 4. Cell surface identity markers 5. Cell-to-cell adhesion proteins 6. Attachments to the cytoskeleton
- 68. Types of MembraneProteins 1. Integral/Transmembrane – attached directly to phospholipids – require detergents to be removed – amphipathic, globular and spans the bilayer (transmembrane) several times in certain proteins – asymmetrically distributed in cell membrane – nonpolar regions of the protein are embedded in the interior of the bilayer – polar regions of the protein protrude from both sides of the bilayer
- 69. 2. Peripheral - donot interact directly with phospholipids - attached to integral proteins - usually found inside the cell - Are free to move throughout one layer of the bilayer - Possess nonpolar regions that are inserted in the lipid bilayer
- 71. C. Carbohydrates • occurin association with lipids or proteins : glycolipids or glycoproteins • mostly found on the external membrane surface • functions : o receptors o antigens o confers negative charge to cell (glycocalyx)
- 73. Fluid-Mosaic Model (Singer &Nicholson) • universally accepted description of membrane structure • “icebergs” (proteins) floating in a “sea” of phospholipids • membranes undergo phasic changes from stiff (gel or crystalline) to fluid state • both lipids and proteins undergo "rapid redistribution" in the plane of the membrane ("lateral diffusion")
- 76. Factors Affecting Membrane Fluidity 1.Lipid composition - longer and more saturated fatty acid chains exhibit higher transition temperature - unsaturated cis bonds tend to increase membrane fluidity - presence of cholesterol the moderator molecule
- 77. 2. Temperature • Atlow temperature – fluidity is less • As temperature increases –increase fluidity • The hydrophobic side chains undergo a transition from ordered state to a disordered state • Transition Temperature (Tm) - temperature at which structure undergoes transition from ordered to disordered state
- 78. 3. Role ofCholesterol • Cholesterol acts as bidirectional regulator of membrane fluidity – At high temperature – it stabilizes the membrane and raises its melting point – At low temperature – it intercalates between the phospholipids and prevents them from clustering together and stiffens • Without cholesterol – Cell membrane would be too fluid, not firm enough and too permeable to some molecules
- 80. Importance of Increased MembraneFluidity 1. Permeability to water and other hydrophilic molecule increases 2. Lateral mobility of integral proteins increases* • * especially important with proteins involved in transport and receptor proteins 3. Increased protein diffusion – since some proteins are internalized, allows for faster appearance
- 81. Artificial Membranes and OtherSpecial Membrane Structures
- 82. A. Micelle • arerelatively small aggregates of amphipathic molecules forming a monolayer with : o hydrophobic regions - shielded from H20 o hydrophilic regions - immersed or interact with H20
- 83. • single-layer unlikecell membrane • arrangement of different regions depends on the chemical environment where the micelle is situated • used in detergents • clinical application of micelles : – are formed when bile acids (which are amphipathic) associate with products of lipid digestion – bile acids-formed micelles assist in the digestion and absorption of fat plus ADEK
- 84. B. Liposomes • Vesiclessurrounded with lipid bilayer • Consist of phospholipids that are of natural or synthetic origin • Lipid content can be varied allowing for examination of varying lipid composition on certain functions (ie., transport) • In the study of factors that affect protein and enzyme function • May be used for specific drug delivery and gene therapy
- 86. C. Tight Junctions •Located below the apical surface of epithelial cells • Prevents the diffusion of macromolecules between them • Composed of proteins occludin, claudins • Sites of paracellular transport • Means of attachment
- 87.
- 88. • Prevents diffusionof macromolecules • Allows paracellular transport of water (e.g. Na+ K+ ATPase) • Physical connection between cells
- 89. D. Gap Junctions •Low resistance connection between cells • More functional connection • Made of connexons (made of connexins) and are aligned with another cell • Transports small ions, molecules, and impulses • In heart muscles, they are known as syncytium
- 90.
- 91. Desmosomes • Junctions whichact like spot welds between adjacent epithelial cells • Involves a complex of proteins, some extend across the membrane while others anchor the junction within the cell • Pin adjacent cells together, ensuring that cells in organs and tissues that stretch, such as skin and cardiac muscle, remian connected in an unbroken sheet. • Cathedrins, specialized adhesion proteins, attach to a structure called the cytoplasmic plaque which connects to the intermediate filaments and helps anchor the junction
- 92.
- 94. E. Lipid Raft •are dynamic areas of the exoplasmic leaflet of the lipid bilayer enriched in cholesterol, sphingolipids and proteins • involved in and enhances signal transduction by clustering elements of the signaling systems
- 97. Caveolae • Derived fromlipid rafts • Usually contain special protein called caveolin-1, which is involved in the formation of lipid rafts • Also takes part in signal transduction
- 98. Special Characteristics ofRed Cell Membrane
- 99. Integral Protein • Twomajor integral proteins in RBC: – Glycophorin – Band-3-protein
- 100. Glycophorin • Glycoproteins; contains60% carbohydrates by weight • Oligosaccharides are linked to serine, threonine and asparagine residues • RBC membrane contains about 6 × 105 glycophorin molecules. • The polypeptide chain of glycophorin contains 130 amino acid residues. – A sequence of 23 hydrophobic amino acid residues lies within the non- polar hydrocarbon phase of the phospholipid bilayer, tightly associated with phospholipids and cholesterol. – This 23 amino acid residue sequence has an α-helical conformation.
- 102. Functions • Some ofthe oligosaccharides of glycophorin are the M and N blood group antigens. • Other carbohydrates bound to glycophorin are sites through which the influenza virus becomes attached to red blood cells.
- 103. Band-3-Protein • Integral proteinfound in red cell membrane. • It is dimeric having molecular weight of 93,000. • The polypeptide chain of the dimer is thought to traverse the membrane about a dozen time. – Both the C and N terminals of band-3-protein are on the cytosolic side of the membrane. – The N-terminal residues extend into the cytosol and interact with components of the cytoskeleton. •
- 104. Functions • plays animportant role in the function of red blood cells. – As red blood cells flow through the capillaries of the lungs, they exchange bicarbonate anions (HCO3–.) produced, by the reaction of CO2 and H2O, for chloride (Cl–) ions. – This exchange occurs by way of a channel in band-3-protein, which forms a Pore through the membrane. .
- 105. Peripheral Protein • Theinner face of the red blood cells membrane is laced with a network of proteins called cytoskeletons that stabilizes the membrane and is responsible for the biconcave shape of the cells: • The special peripheral membrane proteins participate in this stability of red cells are: – Spectrin – Actin – Ankyrin and Band 4, 1 protein.
- 106. Spectrin • Spectrin consistsof an α-chain, having molecular weight 240,000 and a β-chain having molecular weight 220,000. • It is a fibrous protein in which the polypeptide chains are thought to coil around each other to give an α-β dimer, 100 nm long and 5 nm in breadth. • Spectrin dimers are linked through short chains of actin molecules and band 4, 1 proteins to form α2 β2 tetramers.
- 107. Actin • In redblood cells and other nonmuscle cells, actin is a component of the cytoskeleton. • An erythrocyte contains 5 × 105 actin molecules. – About 20 actin molecules polymerise to form short actin filaments.
- 108. Ankyrin • Where thenetwork of spectrin, actin and band 4, 1 protein are attached – These network of protein forms the skeleton of the red blood cell, but none of these proteins is attached directly to the membrane. • It has a molecular weight 200,000. • The protein has 2 domains: One binds to spectrin, and the other to the N-terminal region of band-3-protein that extends into the cytoskeleton. • It is now known that the protein network can also be bound directly to glycophorin (integral protein) or to band-3-protein.
- 109. Clinical Aspect • Hereditaryspherocytosis and hereditary elliptocytosis are inherited genetic abnormalities of red cells in which red cells are of abnormal shape. – In hereditary spherocytosis the red cells are spherical and in hereditary elliptocytosis they are ellipsoidal. – These defects in shape of red blood cells lead to increased haemolysis, anaemia and jaundice. – These abnormally shaped red blood cells are fragile and have shorter life than normal erythrocytes. • Defect: They result from mutations in the genes coding for proteins of the membrane. – The abnormality may be from defective spectrin that is unable to bind either ankyrin or band 4, 1 protein and in some cases band 4, 1 protein is absent.