10/01/2009 biochem: lipids ii lipids ii andy howard introductory biochemistry, fall 2009 01 october...
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10/01/2009Biochem: Lipids II
Lipids II
Andy HowardIntroductory Biochemistry,
Fall 2009 01 October 2009
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Plans for Today Lipids
Glycero-phospholipids
Plasmalogens Sphingolipids Isoprenoids Steroids Other lipids
Membranes Fatty acids Triacylglycerol Glycero-phospholipids
Plasmalogens Sphingolipids Isoprenoids Steroids Other lipids
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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 . . .
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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/
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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
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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
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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)
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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
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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
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Specific plasmalogens
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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
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Sphingolipids Second-most abundant membrane lipids in eukaryotes
Absent in most bacteria Backbone is sphingosine:unbranched C18 alcohol
More hydrophobic than phospholipids
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Varieties of sphingolipids Ceramides
sphingosine at glycerol C3
Fatty acid linked via amideat glycerol C2
Sphingomyelins C2 and C3 as in ceramides
C1 has phosphocholine
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
SphingomyelinImage on steve.gb.com
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Cerebrosides Ceramides with one saccharide unit attached by -glycosidic linkage at C1 of glycerol
Galactocerebrosides common in nervous tissue
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Gangliosides
Anionic derivs of cerebrosides (NeuNAc)
Provide surface markers for cell recognition and cell-cell communication
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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
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Isoprene units: how they’re employed in real molecules
Can be linked head-to-tail … or tail-to-tail (fig. 8.16, G&G)
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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 syntheticallyCholesterol:Yes, you need to memorize this structure!
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Other lipids 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
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Image courtesy cyberlipid.org
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.Image Courtesy Oregon State Hort. & Crop Sci.
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Example of a wax Oleoyl alcohol esterified to stearate (G&G, fig. 8.15)
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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
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Bilayers Self-assembling roughly planar structures
Bilayer lipids are fully extended
Aqueous above and below, apolar within
Solvent
Solvent
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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)
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Salmonella ABC transporter MsbAPDB 3B603.7Å2*64 kDa
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Fluid Mosaic Model depicted
Courtesy C.Weaver, Menlo School
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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)
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Chemical compositions of membranes (fig. 9.10, G&G)
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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
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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
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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
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Integral(Transmembrane) Proteins 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
Drawings courtesy U.Texas
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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
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Chloroflexus auracyaninPDB 1QHQ1.55Å15.4 kDa
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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
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N- Myristoylation & S-palmitoylation
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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
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Transmembrane Traffic:Types of Transport (Table 9.3)Type Protein Saturable Movement
EnergyCarrier w/substr. Rel.to
conc. Input?DiffusionNo No Down NoChannels Yes No Down No & poresPassive Yes Yes Down No transportActive Yes Yes Up Yes
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Cartoons of transport types
From accessexcellence.org
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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.
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Example Suppose [Aout] = 145 mM, [Ain] = 10 mM,T = body temp = 310K
Gtransport = 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