Lipids

Lipids are non-polar (hydrophobic) compounds, soluble in organic solvents. 1. Simple lipids: esters of FA with alcohols Fats: alcohol = glycerol Waxes: alcohol = long-chain alcohol 2. Complex lipids: esters of FA containing groups in addition to an alcohol and FA Phosholipids – contain a phosphoric acid residue Glycolipids – contain carbohydrate 3. Derived lipids: e.g. steroids, carotenoids

Major roles of lipid 1.They serve as structural components of biological membranes. 2. They provide energy reserves, predominantly in the form of triacylglycerols. 3. Lipid derivatives serve as vitamins and hormones. 4. Lipophilic bile acids aid in lipid solubilization. 5. Lipids serve as thermal and electrical insulators.

Fatty acids consist of a hydrocarbon chain with a carboxylic acid at one end. They are amphipathic, having a non-polar end and a polar end. A 16-C fatty acid: CH 3 (CH 2 ) 14 - COO - Non-polar polar FA may be saturated or unsaturated. Fatty Acids

A 16-C fatty acid with one cis double bond between C atoms 9-10 may be represented as: 16:1 cis  9 or 16:1 cis  7  7 - double bond on the seventh carbon counting from terminal methyl carbon

Some fatty acids and their common names: 14:0 myristic acid; 16:0 palmitic acid; 18:0 stearic acid; 18:1 cis  9 oleic acid (  9) 18:2 cis  9,12 linoleic acid (  6) 18:3 cis  9,12,15  -linolenic acid (  3) 20:4 cis  5,8,11,14 arachidonic acid (  6) 20:5 cis  5,8,11,14,17 eicosapentaenoic acid (  3) Double bonds in fatty acids usually have the cis configuration. Most naturally occurring fatty acids have an even number of carbon atoms.

In most FA the hydrocarbon chain is linear. 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. The melting points of FA increase with chain legth and decrease according to unsaturation.

Triacylglycerols Triacylglycerols (triglycerides) are the most abundant dietary lipids. They are the form in which we store energy. Each triacylglycerol has a glycerol backbone to which are esterified 3 fatty acids. Most triacylglycerols are “mixed.” The 3 fatty acids differ in chain length & number of double bonds.

Complex lipids Phospholipids Glycerophospholipids (PE, PS, PC… + plasmalogens) Sphingomyelins Glycolipids Cerebrosides Gangliosides Sphingolipids

Glycerophospholipids Glycerophospholipids (phosphoglycerides), are common constituents of cellular membranes. They have a glycerol backbone. Hydroxyls at C1 & C2 are esterified to fatty acids. An ester forms when a hydroxyl reacts with a carboxylic acid, with loss of H 2 O.

Phosphatidic acid In phosphatidic acid:  fatty acids are esterified to hydroxyls on C1 & C2  the C3 hydroxyl is esterified to P i. Phosphatidic acid is an intermediate in the synthesis of triacylglycerols and glycerophospholipids.

In most glycerophospholipids (phosphoglycerides), P i 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. Usually : R 1 = unsaturated FA R 2 = saturated FA

Each glycerophospholipid includes  a polar region: glycerol, carbonyl of fatty acids, P i, & the polar head group ( X )  non-polar hydrocarbon tails of fatty acids (R 1, R 2 ).  They are amphipathic

Phosphatidylinositol (PI), with inositol as polar head group, is one glycerophospholipid. In addition to being a membrane lipid, phosphatidylinositol has roles in cell signaling.

Phosphatidylcholine (lecithin) PC, with choline as polar head group, is another glycerophospholipid. It is a common membrane lipid. Dipalmitoyl lecithin is major constituent of the surfactant.

Plasmalogens Plasmalogens are glycerol ether phospholipids X They are found in brain and muscle PAF (platelet activating factor) – causes platelet aggregation

The amino group of sphingosine can form an amide bond with a fatty acid carboxyl, to yield a ceramide. Ceramides usually include a polar head group, esterified to the terminal OH of the sphingosine. Sphingolipids are derivatives of the amino alcohol sphingosine, which has a long hydrocarbon tail. Sphingolipids H2NH2N

Sphingomyelin is found in brain and nerve tissue. Sphingomyelin, a ceramide with a phosphocholine head group, is a common constituent of plasma membranes.

head group that is a complex oligosaccharide, including 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. A cerebroside is a sphingolipid (ceramide) with a monosaccharide such as glucose or galactose as polar head group. A ganglioside is a ceramide with a polar

Cholesterol is largely hydrophobic. But it has one polar group, a hydroxyl, making it amphipathic. Cholesterol, an important constituent of cell membranes, has a rigid ring system and a short branched hydrocarbon tail. Steroids 3 17

Cholesterol is the precursor for the synthesis:  D vitamin  Bile acids  Sex hormones  Adrenocortical hormones

Depending on the lipid, possible molecular arrangements:  Various micelle structures. E.g., a spherical micelle is a stable configuration for fatty acids.  A bilayer. This is the most stable configuration for amphipathic lipids such as phospholipids. Amphipathic lipids in association with water form complexes in which polar regions are in contact with water and hydrophobic regions away from water.

Membranes Membrane consists of phospholipids bilayer with proteins inserted in it or bound to the surface. Integral proteins are embedded in the bilayer Peripheral proteins are bound to the surface of the membrane Many of the proteins and lipids carry oligosaccharide chain

In the liquid crystal state, hydrocarbon chains of phospholipids are disordered and in constant motion. At lower temperature, a membrane undergoes transition to a crystalline state in which fatty acid tails are fully extended, packing is highly ordered. Membrane fluidity: The interior of a lipid bilayer is normally highly fluid. cool

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 hydrocarbon tails of phospholipids.

Lateral mobility of a lipid, within the plane of a membrane, is depicted at right. Flip-flopFlip-flop of lipids (from one half of a bilayer to the other) is normally very slow. Flip-flop would require the polar head-group of a lipid to traverse the hydrophobic core of the membrane. The two leaflets of a bilayer membrane tend to differ in their lipid composition.

Lipoproteins Since nonpolar lipids are insoluble in water, for transport in blood they are combined with amphipathic lipids and proteins to make water-miscible lipoproteins Lipoproteins consist of nonpolar core that is surrounded by a layer of phopholipids and cholesterol

Lipoproteins Chylomicrons transport triglycerides from intestine to other tissue Very low density lipoproteins (VLDL) bind triglycerides in liver and curry them to fat tissue Low-density lipoproteins (LDL) carry cholesterol to peripheral tissues High-density lipoproteins (HDL) transport cholesterol to liver