Lipids Lecture Notes PDF

PHRM246 INTRO TO BIOCHEM LIPIDS Dr S Naidoo/PHRM246/Pharm Sciences/Health Sciences/ UKZN  Lipids n Biological compound soluble in non-polar solvent n Chemically heterogeneous: Simple or Complex n Simple Lipid: alcohol + one or more fatty acids n Complex l...

PHRM246 INTRO TO BIOCHEM LIPIDS Dr S Naidoo/PHRM246/Pharm Sciences/Health Sciences/ UKZN  Lipids n Biological compound soluble in non-polar solvent n Chemically heterogeneous: Simple or Complex n Simple Lipid: alcohol + one or more fatty acids n Complex lipid: alcohol + fatty acid + something else  Classification of Lipids Saponification: Usually a process by which triglycerides are reacted with sodium or potassium hydroxide to produce glycerol and a fatty acid salt, called 'soap'. Lipids that contain fatty acid ester linkages can undergo hydrolysis. This reaction is catalyzed by a strong acid or base. In other words, saponification is the alkaline hydrolysis of the fatty acid esters.  Fatty Acids n Linear Molecules 10-20 carbons in length n Even number of carbons n No other functional groups but carboxyl n Sometimes alkene groups C=C n Saturated vs. unsaturated  Water Solubility n Hydrophobic part of molecule dominates: very insoluble in water n Forms micelles in water * * * * * * * *  saturated Fatty Acids to Know Fatty Acid # of Carbons # of C=C lauric 12 0 myristic 14 0 palmitic 16 0 stearic 18 0 A saturated fat is a fat that consists of triglycerides containing only saturated fatty acids. Saturated fatty acids have no double bonds between the individual carbon atoms of the fatty acid chain. That is, the chain of carbon atoms is fully "saturated" with hydrogen atoms. Saturated fatty acids contain only single bond between the carbon atoms and are tend to be solids at room temperature.  Unsaturated Fatty Acids to Know Fatty Acid # of Carbons # of C=C oleic 18 1 linoleic 18 2 linolenic 18 3 arachidonic 20 4 Unsaturated means formation of carbon-carbon double bonds Not all the C in the carbon chains will be saturated with H They are likely to exists as liquids at room temperature.  Melting Points n Increases with size (lesser effect) n Decreases with unsaturation (greater effect) The saturated acids have higher melting points than unsaturated fatty acids of corresponding size The higher melting points of the saturated fatty acids reflect the uniform rod- like shape of their molecules. The cis-double bond(s) in the unsaturated fatty acids introduce a kink in their shape, which makes it more difficult to pack their molecules together in a stable repeating array or crystalline lattice.  Cis vs Trans Fatty Acids n Cis fatty acids occur naturally n Trans fatty acids occur during hydrogenation reactions H H C C CH3CH2CH2CH2CH2CH2 CH2CH2CH2CH2COOH H CH2CH2CH2CH2COOH C C CH3CH2CH2CH2CH2CH2 H Alternate View of Fatty Acids COOH COOH  Triglycerides: Fats and Oils Glycerol + 3 Fatty Acids Connected by ester bonds The tri-esters of fatty acids with glycerol (1,2,3-trihydroxypropane) compose the class of lipids known as fats and oils. These triglycerides (or triacylglycerols) are found in both plants and animals, and compose one of the major food groups of our diet. Triglycerides that are solid or semisolid at room temperature are classified as fats, and occur predominantly in animals. Those triglycerides that are liquid are called oils and originate chiefly in plants, although triglycerides from fish are also largely oils  Triglyceride CH2 OH O CH OH + 3 HO C CH2 OH O CH2 O C O CH O C O CH2 O C  Draw a triglyceride made from stearic, palmitic and myristic acid O CH2 O C O CH O C O CH2 O C O CH2 O C (CH2)14 CH3 O CH O C (CH2)12 CH3 O CH2 O C (CH2)16 CH3  Fat or Oil n Depends on melting point- solid or liquid at room temperature n Depends mostly on degree of unsaturation n Animal Fats more saturated, plant oils more unsaturated  Dietary Fatty Acids n Saturated fats associated with Heart Disease n Promotes higher levels of blood cholesterol n Animal fats also contain cholesterol, plants have no cholesterol  Chemical Properties of Triglycerides 1. Reaction with I2 H H H H + I2 R2 R1 R2 R1 I I Used to quantify degree of unsaturation in fats Product is colorless, I2 is colored Iodine number = grams I2 reacting with 100 g fat  Chemical Properties of Triglycerides 2. Hydrolysis of Ester: catalyzed by acid or enzyme O CH2 O C (CH2)16-CH3 During the process, glycerol is formed, O and the fatty acids react with the base, converting them to salts. CH O C (CH2)16-CH3 +3 H2O O CH2 O C (CH2)16-CH3 H2C OH O HC OH +3 CH3 (CH2)16 C OH H2C OH  Chemical Properties of Triglycerides 3. Saponification with NaOH O The triglyceride is treated with a strong CH2 O C (CH2)16-CH3 base (e.g., lye), which accelerates cleavage of the ester bond and releases the fatty O acid salt and glycerol. This process is the main industrial method CH O C (CH2)16-CH3 for producing glycerol. +3 NaOH The saponification value is the amount of O base required to saponify a fat sample. CH2 O C (CH2)16-CH3 H2C OH O - + HC OH +3 CH3 (CH2)16 C O Na H2C OH n Saponification Reaction produces Soaps Hydrophilic and hydrophobic regions Hydrophobic dissolved in oils Hydrophilic stays on the surface n Insoluble salts form with hard water O - + C O Na Sodium stearate O - + O S O Na O Sodium dodecyl sulfate  Chemical Properties of Triglycerides 4. Hydrogenation H H H H + H 2 Pt R2 R1 R2 R1 H H Reacts with alkene Partial or complete hydrogenation Produces more saturated fat Changes plant oil to margarine Review of Chemical Reactions  Artificial Fats n Simpless: micro-particles of proteins n Smooth cream texture n Not heat stable n 1.3 Cal/gram vs. 9 Cal/gram for fats n Olestra: polymer of sucrose and fatty acids n Not digestable n Taste and texture of fats n Causes loss of fat soluble vitamins and various other side effects n Can cause abdominal cramps and diarrhea n Inhibits fat-soluble vitamins (Vit A, D, E and K) and carotenoids.  Waxes n Long chain fatty acid + long chain fatty alcohol O CH3 (CH2)14 C O CH2 (CH2)12 CH3 Myristyl palmitate  Phosphoglycerides n Glycerol, 2 fatty acids, phosphate + another alcohol Phospholipids are similar to the Fatty Acid triglycerides with a couple of exceptions. Phospho-glycerides are esters of Glycerol Fatty Acid only two fatty acids, phosphoric acid and a tri-functional alcohol The properties of a phospholipid are characterized by the properties of the Phosphate alcohol fatty acid chain and the phosphate/amino alcohol  O CH2 O C (CH2)16-CH3 O Phosphatidic acid CH O C (CH2)16-CH3 O CH2 O P OH OH Alcohols used in phosphoglycerides CH3 HO CH2 CH2 N+ CH3 CH3 choline NH2 O HO CH2 CH C OH HO CH2 CH2 NH2 serine ethanolamine  Phosphatidyl Choline (lecithin) O CH2 O C (CH2)16-CH3 O CH O C (CH2)16-CH3 O CH3 CH2 O P O CH2CH2 N+ CH3 O- CH3 Lecithin used as emulsifier Dipalmitoyl phosphatidyl choline formed as surfactant in lung cells Phosphatidyl serine: a cephalin found in cell membranes O CH2 O C (CH2)16-CH3 O CH O C (CH2)16-CH3 O CH2 O P O CH2 CH NH3+ O- COO-  Sphingolipids: Sphingosine + fatty acid + something else OH CH2 CH2 CH2 CH2 CH2 CH2 CH CH CH2 H3C CH2 CH2 CH2 CH2 CH2 CH2 CH CH OH NH2 CH3 (CH2)12 CH CH CH OH Sphingosine CH NH2 CH OH  Ceramide: sphingosine + fatty acid CH3 (CH2)12 CH CH CH OH O CH NH C (CH2)14 CH3 CH OH CH3 (CH2)12 CH CH CH OH Sphingosine CH NH2 CH OH Sphingomyelin: sphingosine, fatty acid, phosphate and choline Sphingomyelins found in myelin sheath around neurons Make up approx 85% of all sphingolipids, and typically 10-20 mol% of plasma membranes  Sphingomyelin Fatty acid CH3 (CH2)12 CH CH CH OH O CH NH C (CH2)14 CH3 O CH3 CH O P O CH2CH2 N+ CH3 O- CH3 phosphate choline Sphingomyelins contain phospho-choline or phospho-ethanolamine as their polar head group and are therefore classified along with glycero-phospholipids as phospholipids. Sphingomyelins resemble phosphatidyl-cholines in their general properties and three-dimensional structure, and in having no net charge on their head groups. Sphingomyelins are present in the plasma membranes of animal cells and are especially prominent in myelin, a membranous sheath that surrounds and insulates the axons of some neurons, thus the name “sphingomyelins.  Glycolipid: Lipid + Carbohydrate Cerebroside: Sphingosine + fatty acid + carbohydrate CH3 (CH2)12 CH CH CH OH O CH NH C (CH2)14 CH3 H2C OH O HO H2C O OH OH Glycolipids are lipids with a carbohydrate attached. Their role is to provide energy and also serve as markers for cellular recognition. These carbohydrates are found on the outer surface of all eukaryotic cell membranes. Lipid Storage Diseases  Biological Membranes n Separates cell interior from exterior, or cellular organelles from cytoplaslm n About 60% lipid and 40% protein n Lipid mostly phosphoglyceride, sphingomyelin and cholesterol n Found as Lipid Bilayer Lipid Bilayer  Lipid bilayer – arrangement with non-polar phospholipid tails sandwiched in between the polar heads of phospholipids. Cholesterol interspersed throughout Also proteins spanning the double membrane - some of these are ion channels Blood Type Antigens Glc = glucose Gal = galactose GalNAc = N-acetylgalactosamine Fuc = fucose Serum lipids also determine blood groups in blood typing Common structure is made up of ceramide structure, which is made up sphingosine and a fatty acid, and then there is a specific side chain attached  Steroids n Non-saponifiable lipids derived from cholesterol Steroid Ring System  Cholesterol CH3 CH3 CH (CH2)3 CH CH3 CH3 HO Found in Diet (animal fats) Endogenous synthesized in liver  Cholesterol n Essential component of cell membranes n Used as raw material for sex hormones and adreno-corticoid hormones n Used to make bile salts n High blood levels also associated with heart disease, atherosclerosis, arterial plaques Cholesterol transported as Lipoprotein complex (LDL)  Lipoproteins classified by density n HDL: High-density Lipoprotein n LDL: Low-density Lipoprotein n VLDV: Very low-density Lipoprotein n Triglycerides and cholesterol n Chylomicron n Mostly triglycerides Biological flow of Cholesterol  Bile Salts: Glycocholate CH3 O OH CH2 CH3 C CH2 NH CH C O CH3 O- HO OH Act as emulsifying agents to digest fats Method for excreting cholesterol- bile is emulsion of cholesterol and bile salts Gall stones form when cholesterol gets too concentrated  Adreno-corticoid hormones n Gluco-corticoids: regulate blood glucose levels Cortisol and Cortisone Also regulate inflammation, used to treat inflammatory diseases n Mineralo-corticoids: influences blood Na+ and Cl- levels Aldosterone most important  CH2OH CH2OH CH3 C O CH3 C O HO OH O OH CH3 CH3 O O cortisol cortisone O CH2OH CH C O HO OH CH3 aldosterone O  Male Sex Hormones n Testosterone Produced by testes Male genitals and secondary sex characteristics Muscle growth n Anabolic Steroids (fake testosterone) Intended to prevent muscle atrophy Used by athletes, widely banned Severe side effects  Female Sex Hormones n Estrogen(estradiol, estrone) and progesterone Produced by ovaries Reproductive cycle and secondary female characteristics n Mimicked by birth control pills  Prostaglandins n Hormone like action Regulates fever, contractions, inflammation Induces labor, and asthma Made from arachadonic acid Synthesis inhibited by aspirin and cyclooxygenase inhibitors HO COOH CH3 HO HO Classification of Lipids