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Lipids II

Lipids II. Andy Howard Introductory Biochemistry, Fall 2009 01 October 2009. Lipids Glycero-phospholipids Plasmalogens Sphingolipids Isoprenoids Steroids Other lipids. Membranes Fatty acids Triacylglycerol Glycero-phospholipids Plasmalogens Sphingolipids Isoprenoids Steroids

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Lipids II

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  1. Lipids II Andy HowardIntroductory Biochemistry, Fall 2009 01 October 2009 Biochem: Lipids II

  2. Lipids Glycero-phospholipids Plasmalogens Sphingolipids Isoprenoids Steroids Other lipids Membranes Fatty acids Triacylglycerol Glycero-phospholipids Plasmalogens Sphingolipids Isoprenoids Steroids Other lipids Plans for Today Biochem: Lipids II

  3. Varieties of head groups • Variation on other phosphoester position • Ethanolamine (R1-4 = H) (—O—(CH2)2—NH3+) • Serine (R4 = COO-)(—O—CH2-CH-(COO-)—NH3+) • Methyl, dimethylethanolamine(—O—(CH2)2—NHm+(CH3)2-m) • Choline (R4=H, R1-3=CH3) (—O—(CH2)2—N(CH3)3+) • Glucose, glycerol . . . Biochem: Lipids II

  4. Phospholipids aren’t interchangeable! • Phosphatidylcholine and phosphatidylethanolamine are the major components of eukaryotic membranes • Phosphatidylserine and P-inositol tend to be on the inner leaflet only, and are more prevalent in brain tissue than other tissues • Good reference: http://www.lipidlibrary.co.uk/ Biochem: Lipids II

  5. Chirality in common lipids • Fatty acyl chains themselves are generally achiral • Glycerol C2 is often chiral (unless C1 and C3 fatty acyl chains are identical) • Phospholipid polar groups are achiral except for phosphatidylserine and a few others Biochem: Lipids II

  6. iClicker quiz question 3 • What is the most common fatty acid in soybean triglycerides? • (a) Hexadecanoate • (b) Octadecanoate • (c) cis,cis-9,12-octadecadienoate • (d) all cis-5,8,11,14-eicosatetraeneoate • (e) None of the above Biochem: Lipids II

  7. iClicker quiz, question 4 • Which set of fatty acids would you expect to melt on your breakfast table? • (a) fatty acids derived from soybeans • (b) fatty acids derived from olives • (c) fatty acids derived from beef fat • (d) fatty acids derived from bacteria • (e) either (c) or (d) Biochem: Lipids II

  8. iClicker quiz question 5 • Suppose we constructed an artificial lipid bilayer of dipalmitoyl phosphatidylcholine (DPPC) and another artificial lipid bilayer of dioleyl phosphatidylcholine (DOPC).Which bilayer would be thicker? • (a) the DPPC bilayer • (b) the DOPC bilayer • (c) neither; they would have the same thickness • (d) DOPC and DPPC will not produce stable bilayers Biochem: Lipids II

  9. Plasmalogens • Ether phospholipids have an ether link to C1 instead of an ester linking • Plasmalogens are ether phospholipids with C1 linked via cis-vinyl ether linkage. • They constitute the other major category of phospholipids besides esterified glycerophospholipids • Ordinary fatty acyl esterification at C2…platelet activating factor has R2 = CH3 • Usually PE or PC at C3 position Biochem: Lipids II

  10. Specific plasmalogens Biochem: Lipids II

  11. Roles of phospholipids • Most important is in membranes that surround and actively isolate cells and organelles • Other phospholipids are secreted and are found as extracellular surfactants (detergents) in places where they’re needed, e.g. the surface of the lung Biochem: Lipids II

  12. Sphingolipids • Second-most abundant membrane lipids in eukaryotes • Absent in most bacteria • Backbone is sphingosine:unbranched C18 alcohol • More hydrophobic than phospholipids Biochem: Lipids II

  13. Varieties of sphingolipids SphingomyelinImage on steve.gb.com • Ceramides • sphingosine at glycerol C3 • Fatty acid linked via amideat glycerol C2 • Sphingomyelins • C2 and C3 as in ceramides • C1 has phosphocholine Biochem: Lipids II

  14. Cerebrosides • Ceramides with one saccharide unit attached by -glycosidic linkage at C1 of glycerol • Galactocerebrosides common in nervous tissue Biochem: Lipids II

  15. Gangliosides • Anionic derivs of cerebrosides (NeuNAc) • Provide surface markers for cell recognition and cell-cell communication Biochem: Lipids II

  16. Isoprenoids • Huge percentage of non-fatty-acid-based lipids are built up from isoprene units • Biosynthesis in 5 or 15 carbon building blocks reflects this • Steroids, vitamins, terpenes • Involved in membrane function, signaling, feedback mechanisms, structural roles Biochem: Lipids II

  17. Isoprene units: how they’re employed in real molecules • Can be linked head-to-tail • … or tail-to-tail (fig. 8.16, G&G) Biochem: Lipids II

  18. Steroids • Molecules built up from ~30-carbon four-ring isoprenoid starting structure • Generally highly hydrophobic (1-3 polar groups in a large hydrocarbon); but can be derivatized into emulsifying forms • Cholesterol is basis for many of the others, both conceptually and synthetically Cholesterol:Yes, you need to memorize this structure! Biochem: Lipids II

  19. Other lipids Image courtesy cyberlipid.org • Waxes • nonpolar esters of long-chain fatty acids and long-chain monohydroxylic alcohols, e.g H3C(CH2)nCOO(CH2)mCH3 • Waterproof, high-melting-point lipids • Eicosanoids • oxygenated derivatives of C20 polyunsaturated fatty acids • Involved in signaling, response to stressors • Non-membrane isoprenoids:vitamins, hormones, terpenes Image Courtesy Oregon State Hort. & Crop Sci. Biochem: Lipids II

  20. Example of a wax • Oleoyl alcohol esterified to stearate (G&G, fig. 8.15) Biochem: Lipids II

  21. Membranes • Fundamental biological mechanism for separating cells and organelles from one another • Highly selective barriers • Based on phospholipid or sphingolipid bilayers • Contain many protein molecules too(50-75% by mass) • Often contain substantial cholesterol too:cf. modeling studies by H.L. Scott Biochem: Lipids II

  22. Solvent Bilayers • Self-assembling roughly planar structures • Bilayer lipids are fully extended • Aqueous above and below, apolar within Solvent Biochem: Lipids II

  23. Salmonella ABC transporter MsbAPDB 3B603.7Å2*64 kDa Fluid Mosaic Model • Membrane is dynamic • Protein and lipids diffuse laterally;proteins generally slower than lipids • Some components don’t move as much as the others • Flip-flops much slower than lateral diffusion • Membranes are asymmetric • Newly synthesized components added to inner leaflet • Slow transitions to upper leaflet(helped by flippases) Biochem: Lipids II

  24. Fluid Mosaic Model depicted Courtesy C.Weaver, Menlo School Biochem: Lipids II

  25. Physical properties of membranes • Strongly influenced by % saturated fatty acids: lower saturation means more fluidity at low temperatures • Cholesterol percentage matters too:disrupts ordered packing and increases fluidity (mostly) Biochem: Lipids II

  26. Chemical compositions of membranes (fig. 9.10, G&G) Biochem: Lipids II

  27. Lipid Rafts • Cholesterol tends to associate with sphingolipids because of their long saturated chains • Typical membrane has blob-like regions rich in cholesterol & sphingolipids surrounded by regions that are primarily phospholipids • The mobility of the cholesterol-rich regions leads to the term lipid raft Biochem: Lipids II

  28. Significance of lipid rafts:still under discussion • May play a role as regulators • Sphingolipid-cholesterol clusters form in the ER or Golgi and eventually move to the outer leaflet of the plasma membrane • There they can govern protein-protein & protein-lipid interactions • Necessary but insufficient for trafficking • May be involved in anaesthetic functions:Morrow & Parton (2005), Traffic 6: 725 Biochem: Lipids II

  29. Membrane Proteins • Many proteins associate with membranes • But they do it in several ways • Integral membrane proteins:considerable portion of protein is embedded in membrane • Peripheral membrane proteins:polar attachments to integral membrane proteins or polar groups of lipids • Lipid-anchored proteins:protein is covalently attached via a lipid anchor Biochem: Lipids II

  30. Integral(Transmembrane) Proteins Drawings courtesy U.Texas • Span bilayer completely • May have 1 membrane-spanning segment or several • Often isolated with detergents • 7-transmembrane helical proteinsare very typical (e.g. bacteriorhodopsin) • Beta-barrels with pore down the center: porins Biochem: Lipids II

  31. Peripheral Membrane proteins • Also called extrinsic proteins • Associate with 1 face of membrane • Associated via H-bonds, salt bridges to polar components of bilayer • Easier to disrupt membrane interaction:salt treatment or pH Chloroflexus auracyanin PDB 1QHQ1.55Å15.4 kDa Biochem: Lipids II

  32. Lipid-anchored membrane proteins • Protein-lipid covalent bond • Often involves amide or ester bond to phospholipid • Others: cys—S—isoprenoid (prenyl) chain • Glycosyl phosphatidylinositol with glycans Biochem: Lipids II

  33. N- Myristoylation & S-palmitoylation Biochem: Lipids II

  34. Membrane Transport • What goes through and what doesn’t? • Nonpolar gases (CO2, O2) diffuse • Hydrophobic molecules and small uncharged molecules mostly pass freely • Charged molecules blocked Biochem: Lipids II

  35. Transmembrane Traffic:Types of Transport (Table 9.3) Type Protein Saturable Movement Energy Carrier w/substr. Rel.to conc. Input? Diffusion No No Down No Channels Yes No Down No & pores Passive Yes Yes Down No transport Active Yes Yes Up Yes Biochem: Lipids II

  36. Cartoons of transport types • From accessexcellence.org Biochem: Lipids II

  37. Thermodynamics ofpassive and active transport • If you think of the transport as a chemical reaction Ain Aout or Aout Ain • It makes sense that the free energy equation would look like this: • Gtransport = RTln([Ain]/[Aout]) • More complex with charges;see eqns. 9.4 through 9.6. Biochem: Lipids II

  38. Example • Suppose [Aout] = 145 mM, [Ain] = 10 mM,T = body temp = 310K • DGtransport = RT ln[Ain]/[Aout]= 8.325 J mol-1K-1 * 310 K * ln(10/145)= -6.9 kJ mol-1 • So the energies involved are moderate compared to ATP hydrolysis Biochem: Lipids II

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