Lipids. Chapter 11: Outline. Fatty Acids. Lipid Classes. Fatty Acids-2. Fatty Acids-3. General Types eg. A fatty acid

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1 Chapter 11: utline Lipid Classes Fatty Acids and Derivatives Triacylglycerols Phospholipids Isoprenoids Membranes Membrane Structure Membrane Function Wax Esters Sphingolipids Lipoproteins Lipids General Types eg. A fatty acid pen chain: long nonpolar tail with a polar head saponifiable Fused ring based on the steroid ring skeleton Lipid Classes 1. Fatty acids and their derivatives 2. Triacylglycerols 3. Wax esters 4. Phospholipids phosphoglycerides and sphingomyelin 5. Sphingolipids (not sphingomyelin) 6. Isoprenoids (based on isoprene structure) 11-3 Fatty Acids Lauric acid: a typical saturated fatty acid with 12 carbons in the chain (in salt form) Fatty acid: carbons, even # carbons, no branching, nonpolar carbon chain, polar C - group (as anion). C 3 C2 C2 C2 C2 C2 C Nonpolar hydrophobic tail Polar hydrophilic head 11-4 Fatty Acids-2 An unsaturated fatty acid has one or more carbon-carbon double bonds in the chain. The first double bond is usually at the ninth carbon. The double bonds are not conjugated and are usually cis. C C C C 2 Palmitoleic acid, salt form Cis double bond results in a bent chain and lower mp Fatty Acids-3 Stearic 18:0 ( ) 16 C Palmitoleic 16:1 9 ( ) 5 C=C ( ) 7 C Linolenic 18:2 9,12 ( ) 4 C=C C=C( ) 7 C Arachidonic 20:4 5 5,8,11,14 ( ) 3 ( C=C) 4 ( ) 3 C

2 Triacylglycerols When all three alcohol groups of glycerol form esters with fatty acids a triacylglycerol (triglyceride) is formed. Glycerol part C R1 C C R2 C R3 Fatty acid chains 11-7 Triacylglycerols-2 TAGs which are solids at room temperature are rich in saturated acids and are called fats. TAGs which are liquids at room temperature are rich in unsaturated acids and are called oils. e.g. oil seeds include peanut, corn, safflower, palm, and soybean Triacylglycerols-3 Triacylglycerols store fatty acids as fats in animal bodies. Complete oxidation of a fat yields about 38.9 kj/g while carbohydrates yield about 17.2 kj/g. Before a fat can be oxidized, it must be hydrolyzed to the acid anion and glycerol. Biologically this is done by lipases. Chemically base hydrolysis is called saponification Triacylglycerols-4 Saponification (soap making) basic hydrolysis of fats C R3 C 3 Na C C R3 + C R3 3 Na C R3 a soap, Na or K salt of a fatty acid Wax Esters Waxes are typically esters of fatty acids and fatty alcohols. They protect the skin of plants and fur of animal etc. Examples of waxes include carnuba, from the leaves of the Brasilian wax palm, and beeswax. C Phospholipids ave hydrophobic and hydrophilic domains. Structural components of membranes Emulsifying agents Suspended in water they spontaneously rearrange into ordered structures ydrophobic group to center ydrophilic group to water (Next slide) (Basis of membrane structure)

3 Phospholipids-2 Phosphoglycerides When the third of glycerol is esterified to a phosphoric acid or a phosphoric acid ester instead of a carboxylic acid, a phosphoacylglycerol results Phosphatidic acid C R1 C R1 C C R2 C C R2 P P R Phosphatidic ester Phosphatidyl esters, egs. C R1 C C R2 P R R= N 3 + phosphatidylethanolamine N( ) 3 + phosphatidylcholine (lecithin) C P C C R3 C R4 diphosphatidylglycerol (cardiolipin) Sphingolipids These lipids are based on sphingosine, are found in plants and animals, and are common in the nervous system. C C 12 C C N Sphingolipids-2 C C 12 C C 12 C C C N C R1 C N C R1 P N + ( ) 3 A ceramide N-acylsphingosine A sphingomyelin Glycolipids Glycolipids have a carbohydrate bound to the alcohol of a lipid via a glycosidic link. Frequently a glucose or galactose is bound to the primary alcohol of a ceramide. The compound is called a cerebroside. These compounds are found in the cell membranes of nerve and brain cells. Glycolipids have no phosphate. See the next slide for an example

4 Glycolipids-2 C C C C 12 N C A cerebroside R1 Glycolipids-3: Gangliosides Sphingolipids with one or more sialic residues are called gangliosodes. Names include M, D, T (# residues) and subscripts for number of sugars attached to the ceramide Gangleoside GM 2 Sphingolipid Storage Diseases N C C N R C - R = C C Sph Disease Tay-Sachs Gaucher s Krabbe s Sphingomyelin Nieman- Pick Sympt. Blindness, muscle weakenss Liver and spleen enlarge, MR demyelation, MR MR Sph. Lip Ganglioside GM 2 Sphingomyelinase Enzyme β-glucosidase Glucocerebroside β-hexoseaminidasea β-galactosidase Galactocerebroside Isoprenoids Isoprenoids contain a repeating fivecarbon unit know as isoprene. They are synthesized from isopentenyl pyrophosphate. Isoprenoids consist of terpenes and steroids. C C C P isoprene unit isopentenylpyrophosphate P Terpenes Monoterpenes: 2 isoprene units geraniol (in germaniums) Sesquiterpenes: 3 isoprene units farnesene (part of citronells oil) Diterpenes: 4 isoprene units phytol (a plant alcohol) Tetraterpenes: 8 isoprene units cartenoids (orange pigment in plants)

5 Terpenes-2 Some biomolelcule (mixed terpenoids) have isoprenoid (isoprenyl) components. Examples include vitamin E, ubiquinone, vitamin K, and some cytokinins (plant hormones). Some proteins are prenylated (attached to isopreniod groups). Terpenes-3 geraniol farnesene phytol β-carotene Steroids Steroid lipids are based on the ring system shown below. The next slide shows some examples of steroid sex hormones and of cholesterol, a lipid very important in human physiology C D A B Steroid Examples Cholesterol progesterone C C( ) 3 C testosterone Cardiac Glycosides Cardiac glycosides increase the force of cardiac muscle contraction. Digitoxin From digitalis purpurea 3 glycone part aglycone part Lipoproteins The term is most often used for molecular complexes found in blood plasma of humans. Contain: neutral lipid core of cholesterol esters and/or TAGs surrounded by a layer of phospholopid, cholesterol, and protein. Classes: chylomycrons, VLDL, LDL, DL

6 Lipoproteins-2 Chylomycrons: very large and very low density; transport intestineadipose VLDL: made in liver; transport lipids to tissues; depleted one to LDLs. LDL: carry cholesterol to tissues DL: made in liver; scavenge excess cholesterol esters; good cholesterol Atherosclerosis Atheromas (plaque) impede blood flow. Plaque: smooth muscle cells, macrophages, cell debris Macrophages fill with LDLs Coronary artery disease a very common consequence. igh plasma concentrations of LDLs correlate with risk Membranes Each type of cell has a unique membrane composition with varying percentages of lipids, proteins, and some carbohydrates. The currently accepted model of the membrane is the fluid mosaic model of a lipid bilayer. Some examples follow on the next slide. Composition of Some Membranes Protein % Lipid % Carb. % uman erythrocyte Mouse liver Mitochondrial (inner) Spinach lamellar G Guidotti, Ann Rev Biochem, 41:731, Membrane Lipids 1. Fluidity Lateral movement of phospholipids is rapid. Flip-flop, from one side to the other is rare. Increasing percentage of unsaturated fats leads to more fluidity. See next slide. A fluid membrane model

7 Membrane Lipids-2 2. Selective permeability The hydrophobic nature of the membrane makes it impenetrable to the transport of ionic and polar substances. Membrane proteins regulate passage of ionic and polar substances by binding to the polar compound or by providing a channel. Membrane Lipids-3 3. Self-sealing capacity A break in the membrane immediately and spontaneously seals. 4. Asymmetry Bulkier molecules occur more often in the inner side of the membrane Membrane Proteins Most membranes require proteins to carry out their functions. Integral proteins are embedded in and/or extend through the membrane. Peripheral proteins are bound to membranes primarily through interactions with integral proteins. Figure Red Blood Cell Proteins-1 The two major integral proteins of red blood cells are glycophorin and anion channel protein. Glycophorin has 131 AA and is about 60% carbohydrate. Certain oligsaccharides constitute the AB and MN blood up antigens and help to classify blood for transfusion Red Blood Cell Proteins-2 Anion channel protein has two identical 929 AA subunits and plays an important role in C 2 (C 3 - ) transport. C 3 - diffuses through the ion channel in exchange for chloride (chloride shift) and thereby maintains the electrical potential. Red Blood Cell Proteins-3 Peripheral proteins (mainly spectrin, ankyrin, and band 4) help preserve the cells unique biconcave shape. No hemoglobin molecule is more than 1 µm from the cell s surface. This allows for easy diffusion of oxygen

8 Membrane Function Membranes are involved in: Transport of molecules and ions into and out of cells and organelles. Binding of hormones and other biomolecules. Membrane Transport-1 Major types of membrane transport are illustrated below. Fig Membrane Transport-2 Passive transport (no direct energy input) Simple diffusion-molecules move through a membrane down a concentration gradient (toward lower concentration). Facilitated diffusion-molecules move through protein channels in membrane. Membrane Transport-3 Facilitated diffusion Chemically or voltage-regulated e. g. acetyl choline binds to a receptor; Na + rushes into the cell causing depolarization which in turn opens a voltage gated channel for Na +. Repolarizaton begins when a voltagegated K + channel opens and K + leave the cell Membrane Transport-4 Facilitated diffusion (cont.) A carrier protein binds to a molecule. The protein changes conformation and releases the molecule into the cell. This process speeds diffusion but cannot cause a net increase in solute concentration over diffusion limits Membrane Transport-5 Active transport Primary-energy provided by ATP e. g. the Na + -K + pump Secondary-concentration gradients generated by primary active transport are used to move substances across membranes. e. g. Na + gradient (Na + -K + pump) used to transport glucose in kidney tubules

9 Membrane Transport-6 Cystic fibrous is a result of a missing or defective plasma membrane glycoprotein called cystic fibrosis transmembrane conductance regulator (CFTR) which functions as a chloride channel in epithelial cells. In CF, chloride is retained in the cells, thick mucous forms due to osmotic uptake of water in the cells. Chronic pulmonary problems and infections result Membrane Receptors The LDL receptor was discovered during an investigation of familial hypercholesterolemia. When a cell needs cholesterol, it synthesizes the receptor which migrates to a coated region of the membrane. The captured cholesterol is absorbed by endocytosis. Failure to make the receptor is the most common problem encountered