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Lipids II; Membranes

Lipids II; Membranes. Andy Howard Introductory Biochemistry 25 September 2008. Lipids Plasmalogens Glycosphingolipids Isoprenoids Steroids Other lipids Membranes Bilayers Fluid mosaic model Physical properties Lipid Rafts Membrane proteins. Membrane transport Passive & active

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Lipids II; Membranes

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  1. Lipids II; Membranes Andy HowardIntroductory Biochemistry25 September 2008 Biochemistry: Lipid2/Membranes

  2. Lipids Plasmalogens Glycosphingolipids Isoprenoids Steroids Other lipids Membranes Bilayers Fluid mosaic model Physical properties Lipid Rafts Membrane proteins Membrane transport Passive & active Thermodynamics Pores & Channels Protein-mediated transport What we’ll discuss Biochemistry: Lipid2/Membranes

  3. iClicker quiz question 1 • 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 Biochemistry: Lipid2/Membranes

  4. iClicker quiz, question 2 • 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) Biochemistry: Lipid2/Membranes

  5. iClicker quiz question 3 • 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 Biochemistry: Lipid2/Membranes

  6. Plasmalogens • Another major class besides phosphatidates • C1 linked via cis-vinyl ether linkage. • n.b. The textbook figure 8.10 is one page later than the discussion of it • Ordinary fatty acyl esterification at C2 • Phosphatidylethanolamine at C3 Biochemistry: Lipid2/Membranes

  7. Specific plasmalogens Biochemistry: Lipid2/Membranes

  8. 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 Biochemistry: Lipid2/Membranes

  9. Sphingolipids • Second-most abundant membrane lipids in eukaryotes • Absent in most bacteria • Backbone is sphingosine:unbranched C18 alcohol • More hydrophobic than phospholipids Biochemistry: Lipid2/Membranes

  10. 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 Biochemistry: Lipid2/Membranes

  11. Cerebrosides • Ceramides with one saccharide unit attached by -glycosidic linkage at C1 of glycerol • Galactocerebrosides common in nervous tissue Biochemistry: Lipid2/Membranes

  12. Gangliosides • Anionic derivs of cerebrosides (NeuNAc) • Provide surface markers for cell recognition and cell-cell communication Biochemistry: Lipid2/Membranes

  13. 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 Biochemistry: Lipid2/Membranes

  14. 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! Biochemistry: Lipid2/Membranes

  15. 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 Images Courtesy Oregon State Hort. & Crop Sci. Biochemistry: Lipid2/Membranes

  16. Example of a wax • Oleoyl alcohol esterified to stearate (G&G, fig. 8.15) Biochemistry: Lipid2/Membranes

  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) Biochemistry: Lipid2/Membranes

  18. 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 Biochemistry: Lipid2/Membranes

  19. Solvent Bilayers • Self-assembling roughly planar structures • Bilayer lipids are fully extended • Aqueous above and below, apolar within Solvent Biochemistry: Lipid2/Membranes

  20. 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) Biochemistry: Lipid2/Membranes

  21. Fluid Mosaic Model depicted Courtesy C.Weaver, Menlo School Biochemistry: Lipid2/Membranes

  22. 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) Biochemistry: Lipid2/Membranes

  23. Chemical compositions of membranes (fig. 9.10, G&G) Biochemistry: Lipid2/Membranes

  24. 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 Biochemistry: Lipid2/Membranes

  25. 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 Biochemistry: Lipid2/Membranes

  26. 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 Biochemistry: Lipid2/Membranes

  27. 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 Biochemistry: Lipid2/Membranes

  28. 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 Biochemistry: Lipid2/Membranes

  29. 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 Biochemistry: Lipid2/Membranes

  30. N- Myristoylation & S-palmitoylation Biochemistry: Lipid2/Membranes

  31. 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 Biochemistry: Lipid2/Membranes

  32. 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 Biochemistry: Lipid2/Membranes

  33. Cartoons of transport types • From accessexcellence.org Biochemistry: Lipid2/Membranes

  34. 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. Biochemistry: Lipid2/Membranes

  35. 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 Biochemistry: Lipid2/Membranes

  36. Charged species • Charged species give rise to a factor that looks at charge difference as well as chemical potential (~concentration) difference • Most cells export cations so the inside of the cell is usually negatively charged relative to the outside Biochemistry: Lipid2/Membranes

  37. Quantitative treatment of charge differences • Membrane potential (in volts  J/coul):DY = Yin - Yout • Gibbs free energy associated with change in electrical potential isDGe = zFDYwhere z is the charge being transported and F is Faraday’s constant, 96485 JV-1mol-1 • Faraday’s constant is a fancy name for 1. Biochemistry: Lipid2/Membranes

  38. Faraday’s constant • Relating energy per moleto energy per coulomb: • Energy per mole of charges,e.g. 1 J mol-1, is1 J / (6.022*1023 charges) • Energy per coulomb, e.g, 1 V = 1 J coul-1, is1 J / (6.241*1018 charges) • 1 V / (J mol-1) =(1/(6.241*1018)) / (1/(6.022*1023) = 96485 • So F = 96485 J V-1mol-1 Biochemistry: Lipid2/Membranes

  39. Total free energy change • Typically we have both a chemical potential difference and an electrical potential difference so • DGtransport = RTln([Ain]/[Aout]) + zFDY • Sometimes these two effects are opposite in sign, but not always Biochemistry: Lipid2/Membranes

  40. Pores and channels • Transmembrane proteins with centralpassage for small molecules,possibly charged, to pass through • Bacterial: pore. Usually only weakly selective • Eukaryote: channel. Highly selective. • Usually the DGtransport is negative so they don’t require external energy sources • Gated channels: • Passage can be switched on • Highly selective, e.g. v(K+) >> v(Na+) Rod MacKinnon Biochemistry: Lipid2/Membranes

  41. Protein-facilitated passive transport • All involve negative DGtransport • Uniport: 1 solute across • Symport: 2 solutes, same direction • Antiport: 2 solutes, opposite directions • Proteins that facilitate this are like enzymes in that they speed up reactions that would take place slowly anyhow • These proteins can be inhibited, reversibly or irreversibly Diagram courtesy Saint-Boniface U. Biochemistry: Lipid2/Membranes

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