Medical Chemistry and Biochemistry Lecture Notes PDF

MEDICAL CHEMISTRY AND BIOCHEMISTRY FACULTY OF DENTAL MEDICINE DR. AKSU SAMET Lipids  LIPIDS A lipid is an organic substance found in living systems that is insoluble in water but is soluble in organic solvents. Lipids vary widely in their s...

MEDICAL CHEMISTRY AND BIOCHEMISTRY FACULTY OF DENTAL MEDICINE DR. AKSU SAMET Lipids  LIPIDS A lipid is an organic substance found in living systems that is insoluble in water but is soluble in organic solvents. Lipids vary widely in their structures. They have mostly C,H and some have a few polar atoms/ functional groups. Lipids include: fats and oils steroids waxes Fats & oils make up 95% of the nutritional lipids, the other 5% are steroids. Waxes are functional only. Fats are solid triglycerides Oils are liquid triglycerides LIPIDS FATTY ACIDS  FATTY ACIDS THE SIMPLEST LIPIDS ARE THE FATTY ACIDS, WHICH RARELY EXIST ALONE IN NATURE, BUT INSTEAD ARE USUALLY A COMPONENT OF MORE COMPLEX LIPIDS FATTY ACIDS ARE CARBOXYLIC ACIDS WITH A LONG HYDROCARBON CHAIN ATTACHED - SATURATED FATTY ACIDS HAVE ONLY SINGLE BONDS - MONOUNSATURATED FATTY ACIDS HAVE ONE DOUBLE BOND - POLYUNSATURATED FATTY ACIDS HAVE TWO OR MORE DOUBLE BONDS  PHYSICAL PROPERTIES OF SATURATED FATTY ACIDS SATURATED FATTY ACIDS (FATS) HAVE: MOLECULES THAT FIT CLOSELY TOGETHER IN A REGULAR PATTERN STRONG ATTRACTIONS (DISPERSION FORCES) BETWEEN FATTY ACID CHAINS HIGH MELTING POINTS THAT MAKES THEM SOLIDS AT ROOM TEMPERATURE. STRUCTURES AND MELTING POINTS OF SATURATED FATTY ACIDS  PHYSICAL PROPERTIES OF UNSATURATED FATTY ACIDS UNSATURATED FATTY ACIDS (OILS) HAVE: NONLINEAR CHAINS THAT DO NOT ALLOW MOLECULES TO PACK CLOSELY WEAK ATTRACTIONS (DISPERSION FORCES) BETWEEN FATTY ACID CHAINS LOW MELTING POINTS AND SO ARE LIQUIDS AT ROOM TEMPERATURE STRUCTURES AND MELTING POINTS OF UNSATURATED FATTY ACIDS  TRIACYLGLYCEROL TRIACYLGLYCEROLS (ALSO CALLED TRIGLYCERIDES) ARE TRI-FATTY ACID ESTERS OF GLYCEROL TRIACYLGLYCEROLS ARE THE MAJOR FORM OF FATTY ACID STORAGE IN PLANTS AND ANIMALS TRIACYLGLYCEROL'S CAN BE CLASSIFIED AS FATS OR OILS - FATS ARE SOLID AT ROOM TEMPERATURE AND MOST COME FROM ANIMALS - OILS ARE USUALLY LIQUID AT ROOM TEMPERATURE AND COME FROM PLANTS (PALM AND COCONUT OILS ARE SOLIDS AT ROOM TEMPERATURE)  REPRESENTATIVE FATTY ACIDS C12-C18(ALSO C20) DIETARY FATS AND OILS CH3-(CH2)12-COOH (1) CH3-(CH2)14-COOH (2) CH3-(CH2)16-CO2H (3) CH3-(CH2)7-CH=CH-(CH2)7-CO2H (4) CH3-(CH2)4-CH=CH-CH2-CH=CH-(CH2)7-CO2H (5) CH3-CH2-CH=CH-CH2-CH=CH-CH2-CH=CH-(CH2)7-CO2H (6) Name Mp(oC) Class (1) Myristic acid 58 Saturated C-14 (2) Palmitic acid 63 Saturated C-16 (3) Stearic acid 71 Saturated C-18 (4) Oleic acid 4 Monounsaturated C-18 (5) Linoleic acid - 5 Polyunsaturated C-18 (6) Linolenic acid - 11 Polyunsaturated C-18 Fatty Acid Content of some Fats/Oils  Oxidation of Organic Compounds fatty acids O2 -C-C-C-COOH -C-COH-C-COOH saturated difficult O2 -C=C-C-COOH -COH-COH-C-COOH unsaturated easy oxidation = decomposition = rancidity more saturated = more stable, more unsaturated = faster deterioration Hydrolyse: to convert (lyse = to cleave) a compound into other substances through the action of water. -H2O R-C=O R-C=O O-H HO-R’ +H2O O-R’ acid + alcohol ester (fatty acid + glycerol triglyceride) FATTY ACIDS (TRIGLYCERIDES) Solid: longer chains saturated(only C-C) eg. animal fat, butter Liquid: unsaturations (C=C) eg. many vegetable oils (olive, sunflower) Unsaturates can’t fit well into a solid lattice  Reactions (Metabolic) O2 C2 pieces + CO2 + Fatty Acid H 2O + energy * Humans cannot make: * “Essential” Fatty Acids: Linoleic: 18(9,12) Linolenic: 18(9,12,15)  Reactions (“Synthetic”) Iodine # ( sat. unsat.) I I C C C C I I C C C C Iodination H H C C C C H H Hydrogenation unsaturated saturated  Saponification/Hydrolysis of a Triglyceride O O + CH2 O R CH2 OH + R O Na O O 3NaOH / H2O + CH O R' CH OH + R' O Na Heat O O + CH2 O R'' CH2 OH + R'' O Na triglyceride glycerol soaps  Omega - 3 Fatty Acids - Especially in Fish Oils ! Mainly 20 & 22 C’s, polyunsaturated and 1st ‘ene’ is 3 from -end. Eicosapentaenoic acid (EPA): 20(5,8,11,14,17) mp –50OC ! Docosahexaenoic acid (DHA): 22(5,8,11,14,17, 20)  - alpha end COOH  - omega end also -linolenic: 18(9,12,15)  CIS VS. TRANS FATTY ACIDS ALMOST ALL NATURAL UNSATURATED FATTY ACIDS HAVE CIS STEREOCHEMISTRY IN C=C’S. SMALL AMOUNTS OF TRANS ARE PRODUCED IN STOMACHS OF RUMINATING ANIMALS BY PARTIAL ENZYMATIC HYDROGENATION OF POLYUNSATURATED FATS, AND THUS ARE PRESENT IN SMALL AMOUNTS IN MILK AND BUTTER Commercial Hydrogenation of Fatty Acids H H H H H R partial H2 catalyst C C R C C R + C C R R H H R H ‘cis’ ‘trans’ unsaturated saturated unsaturated natural natural unnatural good bad bad ‘Trans’ = Saturated; in shape and ‘badness’ !  H3C Cholesterol - a steroidal alcohol CH3 (atherosclerosis!) CH3 CH3 H3C HO Cholesterol (animal "fat") High – red meat, egg yolks, dairy products Low – egg whites, yoghurt None ! – fruits, veggies, vegetable oils  Properties of Cholesterol very insoluble in water, C27H46O solid, mp. 149o compact, stiff/rigid CELL MEMBRANE STRUCTURE (LIPID BILAYER)  CHOLESTEROL TRANSPORT IN VIVO Cholesterol is insoluble in water, hence to transport it through the bloodstream, our bodies wrap it in a sheath of proteins and varying amounts of triglycerides to form lipoproteins. High Density Lipoproteins (HDL’s) transport excess cholesterol to the liver for disposal “good cholesterol” LDL’s (Low Density Lipoproteins) and VLDL’s tend to deposit cholesterol on arterial walls “bad cholesterol”  STRUCTURAL FEATURES: HDL VS LDL HDL contains unsaturated cis Fatty acids LDL contains more saturated and trans fatty acids Both contain apolipoproteins and phospholipids which are oriented with hydrophobic part on inside and outer hydrophilic edges exposed  Fat and Oil Content Food Cholesterol Saturated Monounsaturated Polyunsaturated Beef 91 2.7 2.7 0.5 Butter 219 50.5 23.4 3 Cheese ,cheddar 105 21.1 9.4 0.9 Cheese , cottage dry 7 0.3 0.1 0.02 Chicken (no skin) 85 1.3 1.5 1 Corn oil 0 12.7 24.2 58.7 Eggs , whole 548 3.4 4.5 1.4 Frankfurter (all beef) 51 12.7 14.8 1.2 Margarine,stick(coin oil ) 0 13.2 45.8 18 Milk , skim 2 0.1 0.05 0.007 Milk whole 14 2.3 1.1 0.1 Olive oil 0 13.5 73.7 8.4 Peanut butter 0 9.7 23.3 15.2 Peanut oil 0 16.9 46.2 32 Safflower oil 0 9.1 12.1 74.5 Salmon (pink , canned) 35 1 1.8 2.7 Tuna (canned in water ) 63 0.2 0.1 0.2 Turkey (no skin ) 69 1 0.6 0.9 Yogurt (plain , lowfat) 6 1 0.4 0.04  CHOLESTEROL RELATED COMPOUNDS 7-dehydrocholesterol (functions as a cholesterol precursor in blood serum) gets converted in vivo (epidermal cells) to Vitamin D by the action of sunlight  Phospholipids nonpolar tails (HC ) ‘-’ or R polar head (charged) a phosphatidic acid Phospholipid Bilayer = Cell Membrane/Wall -water outside cell- hydrophilic surface hydrophobic interior of cell wall -water inside cell- Phosphoglyceride Aggregate = Cell Wall -cell exterior- -cell interior-  Lecithin - Another Phospholipid (emulsifying agent in egg yolks for mayonnaise, candy, cake dough)  LIPIDS IN EGG YOLK ~ 66% FAT, 30% PHOSPHOLIPID (LECITHIN), 4% CHOLESTEROL LECITHIN (~2 GRAMS PER YOLK) ACTS AS AN EMULSIFIER TO “SOLUBILIZE’’ THE FAT IN THE WATER OF THE YOLK EGG YOLKS USED COMMERCIALLY TO PRODUCE MAYONNAISE, AN EMULSION  ORIGIN OF PHOSPHOLIPIDS BIOSYNTHESIZED IN HUMANS FROM GLYCEROPHOSPHATE AND FATTY ACID COA ATP (ADENOSINETRIPHOSPHATE) IS NEEDED AS A PHOSPHORYLATING AGENT Soy Lecithin: comes from soybean oil  LECITHIN IN CHOCOLATE ACTS AS SURFACTANT (0.5 TO 1%) TO AID IN THE FLOW OF LIQUID CHOCOLATE POLAR END SURROUNDS SUGARS ( OH GROUPS) NON POLAR END INTERACTS WITH FAT HERSHEY PLANT (SMITHS FALLS) CLOSING 2006 DUE TO SALMONELLA IN SOY LECITHIN (DEC 2/06 REOPENING)-THEN PERMANENT CLOSURE IN 2007. SALMONELLA BACTERIA (NORMALLY FROM UNDERCOOKED POULTRY) ENTER SMALL INTESTINE CAUSING INFECTION  Waxes = (large mol.wt.) Esters (R-COOR’) Birds/insects - water repellant feathers/exoskeletons Leaves/fruit - minimize water evaporation Humans - to plug up ears! beeswax; R= C15, R’= C30; carnauba wax(Brazilian palm): R= C31, R’= C34 Whales have 4 tons*(in head). While swimming on surface(37oC) it is a liquid. When they dive (1000m) to feed, the oil solidifies, increases in density, and whale can stay submerged without effort until ready to return to surface where oil remelts for buoyancy.  DENSITY OF SOLIDS VS. LIQUIDS Behavior of whale oil is normal-ie liquid is less dense than the solid Water is the only substance on the planet in which the solid (ice) is less dense than the liquid Water at 4oC is the most dense!  Soaps/Detergents Contain a nonpolar fat component (tail) and a polar head Bipolar Behaviour of Soaps, etc.  CH3(CH2)8 SO3- Na+ alkylbenzene sufonate(anionic) Detergents = CH3(CH2)13OSO3– Na+ alkyl sulfate(anionic) Synthetic Soaps ie. hydrocarbon tail + CH3(CH2)8O(CH2CH2O)nH polar/charged head (nonionic) CH3(CH2)11N+(CH3)Cl – trimethylalkylammonium(cationic)  A Typical Soap Molecule hydrophyllic hydrophobic ‘loves’ H2O ‘hates’ H2O Soap makes Grease ‘water-soluble’  SOAPS IN HARD WATER Curd formation due to insoluble Fe, Ca and Mg carboxylates Water softeners: exchange Na for Fe, Ca and Mg ions, increasing solubility of the carboxylates Detergents function better in hard water because sulfonates are soluble