Lec2 lipids and cell membrane

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Lec2 lipids and cell membrane

  1. 1. 1. Monosaccharides are aldehydes or ketones with multiple hydroxyl groups. 2. Complex carbohydrates are formed by linkage of monosacchrides. 3. Carbohydratea can attach to proteins to form glycoproteins. 4. Lectins are specific carbohydrate-binding proteins mediating Cell-Cell interaction. On Monday:
  2. 2. Monosaccharides can be modified by reaction with alcohols and amines to form adducts O-Glycosidic bond: between the anomeric carbon atom of glucose and the hydroxyl oxygen atom of methonol. N-Glycosidic bond: anomeric carbon atom – nitrogen atom of an amine
  3. 3. Complex carbonhydrate are formed by linkage of monosacchrides Monosaccharides Oligosaccharides O-glycosidic bonds
  4. 4. Formation of a mannose 6-phosphate 1. Mannose 6-phosphate is a marker directing certain proteins from the Golgi to lysosomes. 2. Deficient in the phosphotransferase I-cell disease (psychomotor retardation + skeletal deformities) Can’t form mannose 6-phosphate Mistargeting of essential enzymes (lysosome blood and urine)
  5. 5. Lipids and Cell Membrane
  6. 6. Structure of biomembrane Head group Fatty acid
  7. 7. Electron micrograph of red blood cell plasma membrane
  8. 8. Electron micrograph of red blood cell plasma membrane
  9. 9. Confocal image of ERD-GFP (an ER marker)
  10. 10. Common feagures of biological membrane 1. Membranes are sheetlike structures, only two molecules thick, that form closed boundaries between different compartments. The thickness of most membranes is between 6 nm and 10 nm. 2. Membrane consist mainly of lipids and proteins. Their mass ratio ranges from 1:4 to 4:1. Membranes also contain carbohydrates that are linked to lipids and proteins. 3. Membrane lipids have both hydrophilic and hydrophobic moieties. These lipid bilayers are barriers to the flow of polar molecules. 4. Specific proteins mediate distinctive functions of membrane.
  11. 11. 5. Membranes are noncovalent assemblies. The constituent proteins and lipid molecules are held together by many noncovalent interactions. 6. Membranes are asymmetric. The two faces of biological membranes always differ from each other. 7. Membranes are fluid structures.lipid and protein molecules diffuse rapidly , unless they are anchored by specific interactions. Membranes can be regarded as two-dementional solutions of oriented proteins and lipids. 8. Most cell membranes are electrically polarized. Membrane potential plays a key role in transport, energy conversion, and excitability. Common feagures of biological membrane
  12. 12. Fatty Acids are key conponents of lipids Structure of biomembrane Head group Fatty acid
  13. 13. <ul><li>General Features of Fatty Acid Structure </li></ul><ul><li>The elements of fatty acid structure are quite simple. There are two essential features: </li></ul><ul><li>1. A long hydrocarbon chain </li></ul><ul><ul><li>● The chain length ranges from 4 to 30 carbons; 12-24 is most common. </li></ul></ul><ul><ul><li>● The chain is typically linear, and usually contains an even number of carbons. </li></ul></ul><ul><li>2. A carboxylic acid group </li></ul>The many fatty acids which occur naturally arise primarily through variation of chain length and degree of saturation.
  14. 14. Carbon-Carbon Double Bonds Carbon-carbon double bonds (unsaturations) are found in naturally occurring fatty acids. There may be one double bond or many, up to six in important fatty acids. Fatty acids with one double bond are the most prevalent in the human body, comprising about half of the total. Fatty acids with two or more double bonds occur in lesser quantities, but are extremely important. When double bonds occur they are almost always cis. If there is more than double bond, they occur at three-carbon intervals, e.g., -C=C-C-C=C-. This is called the divinylmethane pattern.
  15. 15. Classification of Fatty Acids One system of fatty acid classification is based on the number of double bonds. ● 0 double bonds: saturated fatty acids ● 1 double bond: monounsaturated fatty acids
  16. 16. ● 2 or more double bonds: polyunsaturated fatty acids
  17. 17. Phospholipids are the major class of membrane lipids Hydrophobic hydrophilic Amphipathic
  18. 20. Cholesterol is a lipid based on a steriod Nucleus
  19. 21. Cholesterol is a lipid based on a steriod Nucleus 4 linked hydrocarbon rings
  20. 22. Cholesterol is a lipid based on a steriod Nucleus Interact with phospholipid head group
  21. 23. A micelle Membrane formation is a consequence of the amphipathic nature of the lipids
  22. 24. A section of a bilayer membrane leaflets
  23. 25. The favored structure for most phospholipids and glycolipids in aqueous media is a bimolecular sheet rather than a micelle.
  24. 26. Hydrophobic interactions have three significant biological consequences: 1. Lipid bilayers have an inherent tendency to be extensive. 2. Lipid bilayers tends to close on themselves so that there are no edges with exposed hydrocarbon chains, and so they form compartments. 3. Lipid bilayer are self-sealing because a hole in a bilayer is energetically unfavorable.
  25. 28. Preparation of glycine-containing liposomes (size ~ 50nm).
  26. 29. Proteins carry out most membrane processes
  27. 30. SDS-acrylamide gel patterns of membrane proteins
  28. 31. Immunofluorescent staining of a plasmamembrane protein
  29. 32. Proteins associate with the lipid bilayer in a variety of ways Integral membrane protein: a, b, c. Peripheral membrane protein: d, e.
  30. 33. Proteins interact with membranes in a variety of ways Protein can span the menrane with alpha helices which are the most common structural motif in membrane proteins.
  31. 34. A channel protein can be formed from Beta strands hydrophilic hydrophobic
  32. 38. Lipids and many membrane proteins diffuse rapidly in the plane of the membrane FRAP: Fluorescence recovery after photobleaching
  33. 39. The fluid mosaic model allows lateral movement but not rotation through the membrane
  34. 40. Membrane fluidity is controlled by fatty acid composition and cholesterol content
  35. 41. ● All biological Membranes asymmetric. ● The outer and inner surface of all known biological membranes have different components and different enzymatic activities.
  36. 42. P roteins are targeted to specific compartments by signal sequences
  37. 43. P roteins are targeted to specific compartments by signal sequences
  38. 44. P roteins are targeted to specific compartments by signal sequences
  39. 45. C 473 C 482 FVIFIVVQTVLFIGYIMY ERQQEAAAKKFF CRD Luminal domain TMD cytoplasm tail P58-YFP C473L-YFP C482L-YFP C473L/C482L-YFP P58-YFP C473L-YFP C482L-YFP C473L/C482L-YFP-YFP 6  2  1 
  40. 47. Summary ○ M any common features underlie the diversity of biological membrane ○ Fatty acid are key constituents of lipid ○ There are three common types of membrane lipids: phosphlipids, glycolipids and cholesterol. ○ Protein associate with the lipid bilayer in a variety of way. ○ Lipids and many membrane proteins diffuse rapidly in the plane of the membrane
  41. 48. Selectec readings De Weer, P. 2000. a century of thinking about cell membranes. Annu. Rev. Physiol. 62: 919-926 W hite SH and wimley WC. 1999. Membrane protein folding and stability: Physical principles. Annu. Rev. Biophys. Biomol. Struct. 28: 319-365. Gunnar von Heijne. 2006. Membrane-protein topology. Nature Reviews Molecular Cell Biology 7, 909 – 918 John F. Hancock. 2006. Lipid rafts: contentious only from simplistic standpoints. Nature Reviews Molecular Cell Biology 7, 456-462

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