Lipids & Membranes PDF

Lipids & Membranes Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents. Most membrane lipids are amphipathic, having a non-polar end and a polar end. Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end. A 16-C fatty acid: CH3(CH2)14-COO-...

Lipids & Membranes Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents. Most membrane lipids are amphipathic, having a non-polar end and a polar end. Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end. A 16-C fatty acid: CH3(CH2)14-COO- Non-polar polar A 16-C fatty acid with one cis double bond between C atoms 9-10 may be represented as 16:1 cis D9.  O Double bonds in fatty   a C  acids usually have the 4 3 1 O 2 cis configuration. Most naturally fatty acid with a cis-D9 occurring fatty acids double bond have an even number of carbon atoms. Some fatty acids and their common names: 14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid; 18:1 cisD9 oleic acid 18:2 cisD9,12 linoleic acid 18:3 cisD9,12,15 a-linonenic acid 20:4 cisD5,8,11,14 arachidonic acid 20:5 cisD5,8,11,14,17 eicosapentaenoic acid (an omega-3)  O   a C 4 3 1 O 2 fatty acid with a cis-D9 double bond There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond. Each cis double bond causes a kink in the chain. Rotation about other C-C bonds would permit a more linear structure than shown, but there would be a kink.  Glycerophospholipids Glycerophospholipids CH2OH (phosphoglycerides), are common constituents of cellular membranes. H C OH They have a glycerol backbone. CH2OH Hydroxyls at C1 & C2 are esterified glycerol to fatty acids. An ester forms when a hydroxyl Formation of an ester: reacts with a O O carboxylic acid, with loss of H2O. R'OH + HO-C-R" R'-O-C-R'' + H2O  Phosphatidate O O H2C O C R2 R1 C O CH O H2C O P O O phosphatidate In phosphatidate:  fatty acids are esterified to hydroxyls on C1 & C2  the C3 hydroxyl is esterified to Pi.  O O H2C O C R2 R1 C O CH O H2C O P O X O glycerophospholipid In most glycerophospholipids (phosphoglycerides), Pi is in turn esterified to OH of a polar head group (X): e.g., serine, choline, ethanolamine, glycerol, or inositol. The 2 fatty acids tend to be non-identical. They may differ in length and/or the presence/absence of double bonds.  O O H2 C O C R2 R1 C O CH O H2 C O P O O H OH OH H OH OH H phosphatidyl- H H inositol H OH Phosphatidylinositol, with inositol as polar head group, is one glycerophospholipid. In addition to being a membrane lipid, phosphatidylinositol has roles in cell signaling.  O O H2C O C R2 R1 C O CH O CH3 + H2C O P O CH2 CH2 N CH3 O CH3 phosphatidylcholine Phosphatidylcholine, with choline as polar head group, is another glycerophospholipid. It is a common membrane lipid.  O O H2C O C R2 Each glycerophospholipid R1 C O CH O includes  a polar region: H2C O P O X glycerol, carbonyl O O of fatty acids, Pi, & the glycerophospholipid polar head group (X) polar  non-polar hydrocarbon tails of fatty acids (R1, R2). "kink" due to double bond non-polar  OH OH Sphingolipids are derivatives of H the lipid sphingosine, which has a H2C C CH long hydrocarbon tail, and a polar H3N+ CH domain that includes an amino group. HC O (CH2 )12   O P O sphingosine CH3 O OH H H2C C CH Sphingosine may be reversibly H3N+ CH phosphorylated to produce the signal molecule sphingosine-1-phosphate. HC Other derivatives of sphingosine are (CH2 )12 commonly found as constituents of sphingosine-1-P CH3 biological membranes.  OH OH H H2C C CH The amino group of sphingosine can H3N+ CH form an amide bond with a fatty acid HC carboxyl, to yield a ceramide. (CH2 )12 OH OH sphingosine CH3 H H2C C CH NH CH O C HC In the more complex sphingolipids, R (CH2 )12 a polar “head group" is esterified ceramide CH3 to the terminal hydroxyl of the sphingosine moiety of the ceramide.  CH3 O H2 H2  + H3C N C C O P O Sphingomyelin has CH3 O OH a phosphocholine or phosphocholine H H2C C CH phosphethanolamine head group. sphingosine NH CH Sphingomyelins are O C HC common constituent fatty acid R (CH2 )12 of plasma membranes Sphingomyelin CH3 Sphingomyelin, with a phosphocholine head group, is similar in size and shape to the glycerophospholipid phosphatidyl choline.  CH2OH A cerebroside is a OH O sphingolipid H O OH OH H (ceramide) with a H H2C H C CH H monosaccharide H OH NH CH such as glucose or galactose as polar O C HC head group. R (CH2 )12 A ganglioside is a cerebroside with -galactose head group CH3 ceramide with a polar head group that is a complex oligosaccharide, including the acidic sugar derivative sialic acid. Cerebrosides and gangliosides, collectively called glycosphingolipids, are commonly found in the outer leaflet of the plasma membrane bilayer, with their sugar chains extending out from the cell surface. Amphipathic lipids in association with water form complexes in which polar regions are in contact with water and hydrophobic Bilayer Spherical Micelle regions away from water. Depending on the lipid, possible molecular arrangements:  Various micelle structures. E.g., a spherical micelle is a stable configuration for amphipathic lipids with a conical shape, such as fatty acids.  A bilayer. This is the most stable configuration for amphipathic lipids with a cylindrical shape, such as phospholipids. Membrane fluidity: The interior of a lipid bilayer is normally highly fluid. liquid crystal crystal In the liquid crystal state, hydrocarbon chains of phospholipids are disordered and in constant motion. At lower temperature, a membrane containing a single phospholipid type undergoes transition to a crystalline state in which fatty acid tails are fully extended, packing is highly ordered, & van der Waals interactions between adjacent chains are maximal. Kinks in fatty acid chains, due to cis double bonds, interfere with packing in the crystalline state, and lower the phase transition temperature. Cholesterol, an important constituent of cell membranes, has a rigid ring system and a short HO branched Cholesterol hydrocarbon tail. Cholesterol is largely hydrophobic. But it has one polar group, a hydroxyl, making it amphipathic. PDB 1N83 cholesterol  HO Cholesterol Cholesterol in membrane Cholesterol inserts into bilayer membranes with its hydroxyl group oriented toward the aqueous phase & its hydrophobic ring system adjacent to fatty acid chains of phospholipids. The OH group of cholesterol forms hydrogen bonds with polar phospholipid head groups. Interaction with the relatively rigid cholesterol decreases the mobility of Cholesterol hydrocarbon tails of phospholipids. in membrane But the presence of cholesterol in a phospholipid membrane interferes with close packing of fatty acid tails in the crystalline state, and thus inhibits transition to the crystal state. Phospholipid membranes with a high concentration of cholesterol have a fluidity intermediate between the liquid crystal and crystal states. Two strategies by which phase changes of membrane lipids are avoided:  Cholesterol is abundant in membranes, such as plasma membranes, that include many lipids with long-chain saturated fatty acids. In the absence of cholesterol, such membranes would crystallize at physiological temperatures.  The inner mitochondrial membrane lacks cholesterol, but includes many phospholipids whose fatty acids have one or more double bonds, which lower the melting point to below physiological temperature. Glycosylphosphatidylinositols (GPI) are complex glycolipids that attach some proteins to the outer surface of the plasma membrane. The linkage is similar to the following, although the oligosaccharide composition may vary: protein (C-term.) - phosphoethanolamine – mannose - mannose - mannose - N-acetylglucosamine – inositol (of PI in membrane) The protein is tethered some distance out from the membrane surface by the long oligosaccharide chain. GPI-linked proteins may be released from the outer cell surface by phospholipases.  Differences in molecular shape may contribute to a tendency for sphingolipids to separate out from glycerophospholipids in membrane microdomains. Sphingolipids usually lack double bonds in their fatty acid chains. Glycerophospholipids often include at least one fatty acid that is kinked, due to one or more double bonds.