Lipid Chemistry PDF

Lipid Chemistry By Prof. Dr. Abdellah Ali Omar M.B.B.Ch, MS, M.D Professor of Medical Biochemistry 11/02/1443 1  Lipids are a Heterogeneous Group of Organic Compounds Related to Fatty Acids Relatively Insolubl...

Lipid Chemistry By Prof. Dr. Abdellah Ali Omar M.B.B.Ch, MS, M.D Professor of Medical Biochemistry 11/02/1443 1  Lipids are a Heterogeneous Group of Organic Compounds Related to Fatty Acids Relatively Insoluble in Water ( Hydrophobic = Water Hating ) due to Predominance of Hydrocarbon chain & Soluble in Non-Polar Solvents Such as Ether, Benzene, Chloroform & Acetone  Lipids are the Most Efficient Form of Stored Energy in Humans Together with Carbohydrate & Protein, Form major Diet Excess lipids is Stored as Fat  Examples of Lipids - Fatty acids - Tri-Acylglycerol - PhosphoLipids - GlycoLipids - SphingoLipids - Steroids - Vitamins A, D, E, K  Lipids Classified Into Simple Conjugated Derived ( Compound ) Neutral fat Waxes Glycerol + FAs Higher Alcohol + FA Neutral fat ( Because it Carry No Charges )  Simple Lipids a – Fats (Acylglycerol): Esters of Fatty acids with Glycerol e.g. Triglycerides ( if 3 FA ) b – Waxes: Esters of Fatty acids with Higher alcohols ( alcohols other than glycerol e.g. beewax, lanolin ) 6 II - Complex Lipids Are Esters of Fatty acids with Alcohol in addition to Other Groups e.g. - Phospholipids ( subclassified into ) a - GlyceroPhosphoLipids b - SphingoPhosphoLipids - SphingoLipids ( With or Without Phosphate ) a Glycolipids b Sulfolipids c Gangliosides d Mucolipids - Proteolipids (Lipoprotein) 7 III – Derived Lipids Any Substance can be Given by Hydrolysis of Simple or Complex Lipid e.g. Fatty Acids Steroids Fat Soluble Vitamins ( A, D, E, K ) Ketone Bodies Carotenoids BioMedical Importance of Lipids In diet: - Source of High Energy - Contain Fat Soluble Vitamins - Contain Essential Fatty Acids - Make Diet Palatable  In Body: - Adipose Tissue serve as Storage Form of Energy - Thermal Insulator in Subcutaneous Tissue - Electrical Insulator in Nervous Tissue ( allow Rapid Propagation ) - Enter in Lipoprotein Formation ( Enter in Cell Membrane Structure & Act as Transport form of Energy in Blood )  Neutral Fats [ Tri Acyl Glycerol ] Neutral fat ( Triacylglycerol ) Esters of 3 Fatty acids with Glycerol Glycerol is Short Chain Alcohol containing 3 OH groups Types: Simple : contain Similar Fatty Acids e.g., Tripalmitin & Triolein Mixed : contain Different Fatty Acids e.g., Palmito-Oleio-Stearin & Di-Stearin Palmitin Either Solid, called Fats or Liquid, called Oils 14 Fatty Acids (FA)  Fatty acids are Long Chain Organic Molecules Containing Carboxylic end ( COOH ) Either : 1 - Saturated No Double Bonds, Non Essential 2 - Unsaturated contain One or More Double Bonds Either Essential & Non essential - Water Insoluble Long Chain Hydrocarbons - May be Saturated or Unsaturated - Mostly Mono-Carboxylic Acids - Mostly Aliphatic ( No Branches ) acids - Occur Mainly as Esters in Neutral fats - Can Occur Freely in Plasma - Fatty acids in Neutral Fats contain an Even ( ‫ ) زوجى‬Number of Carbons Saturated FA Mono-Un-Saturated FA Poly-Un-Saturated FA  Saturated FA ( Anoic ) No Double Bonds ( No C=C ) General Formula is CH3 - (CH2)n - COOH Where (n) is Number of Methylene Group (CH2)  Examples of Important Saturated FA: Butyric acid ( 4C ): CH3 – CH2 – CH2 – COOH Caproic acid ( 6C ): CH3 – (CH2)4 – COOH Palmitic acid ( 16C ): CH3 – (CH2)14 – COOH Stearic acid ( 18C ): CH3 – (CH2)16 – COOH  Saturated Fatty Acids Common Name C- Atoms Source & Significance Butyric Acid 4 Fats, Butter, end product of CHO Caproic Acid 6 fermentation of rumen organisms Capyrlic Acid 8 Fats, butter, fats of plant origin. Provide energy to body. Capric ( Decanoic) 10 Coconut oil, palm, butter, cinnamon, Lauric Acid 12 spermaceti provide energy Mysristic Acid 14 Nuts, Palm, Coconut, butter, provide energy Palmitic Acid 16 Common in all animal & plant fat. Stearic Acid 18 Provide energy and structure. Arachidic Acid 20 Peanut-arachis oil. Provide energy Behenic Acid 22 Seeds, nuts. Provide energy Lignoceric Acid 24 Peanuts, cerebrosides  Carbon Skeleton of Fatty Acid Numbered Either 1 - From the Carboxylic Group (COOH) - ( Delta = ∆ ) or - Alpha, Beta, Gamma, Delta, Epsilon ∆ 6 5 4 3 2 1 CH3-CH2-CH2-CH2-CH2-COOH ε δ γ β α ω1 2 3 4 5 6 2 - From the Terminal Methyl Group ( Omega=ώ )  Non Essential FA: They Can be Synthesized in the Body from Acetyl CoA (Common Metabolic Pool) They are the Saturated & MonoUnSaturated FA Unsaturated Fatty Acids (Enoic) Fatty acids Containing Double Bond(s) They are Either MonoUnSaturated (one Double Bond) or PolyUnSaturated (More than One Double Bond) General Formula is Cn – H2n-1 – COOH Where (n) is the Number of Carbon Atoms Without COOH  Double Bonds are: Nearly always in Cic Configuration Spaced at 3 Carbon Interval if the Fatty Acid has More than one double bond  Mono UnSaturated FA  MonoUnSaturated FA MonoEnoic Fatty acids MonoThenoic Fatty acids ( Non Essential ): Example Palmitoleic (16C) is written 16:1 Δ9 , 16:1 ώ7 Oleic = OctaDecaEnoic (18C) is written 18:1 Δ9 PolyUnSaturated FA ( Essential ): PolyEnoic fatty acids PolyThenoic fatty acids  Essential FA: Linoleic acid (18C) is written 18: 2 ∆9,12, ώ6,9 Linolenic acid (18C) is written 18:3 ∆9,12,15 , ώ3,6,9 Present in Linseed oil Arachidonic acid (20C) is written 20: 4 ∆5,8,11,14, ώ6 Present in Peanut Oil Precursor of Eicosanoids Component of Phospholipids in Animals Clupanodonic acid (22C) is written 22: 5 ∆7,10,13,16,19, ώ3 Present in Fish Oil Component of Phospholipids in Brain  Essential Fatty acids (EFA) Must be Supplied in the Diet because the Body Can Not Synthesize Them We Lack Enzymes Required to Introduce Double Bonds after C9 Our Human Body has Enzyme System that can ‫يضيف بين‬ Form Only One Double Bond at ∆ ‫فى اتجاه ال‬ 9 ‫يضيف‬ C 9-10 COOH  Essential Fatty acids (EFA): Present Mainly in Vegetable Oils e.g. Corn Oil, Soya Bean Oil, Sun Flower Oil & Cotton Seed Fish oils e.g. Shark Liver Oil & Tuna Contain ώ3 PUFA Arachidonic acid (20C) is formed in the Body from Linoleic acid Becomes Essential Only If Linoleic acid is Deficient  Essential Fatty Acids: Synthesized Only by Plants but Required by Humans Linoleic (ω-3) & Linolenic acids (ω-6) Non-Essential Fatty Acids: Humans Synthesize them - From Other Fatty Acids or - From Other Precursors, Derived From Other Foodstuff  Unsaturated Fatty Acids Name Source & Significance Monoenoic. In all fats provide energy Palmito-Oleic 7 Oleic Acid 9 Most common in natura fats. Dienoic. Corn, peanut, cotton seed, Lenoleic 6 Soyabean, EFA. Trienoic. Linseed oils & others.  Lenolenic 3 Essential fatty acids (EFA)  Lenolenic 6 Minor FA in animals.EFA Arachidonic 6 Tetraenoic. In animal fat & peanut oil.EFA Timmodonic 3 Pentaenoic. Fish oil, cod liver, salmon oil. Hexaenoic. Fish oil & PL in brain Nervonic 3 Natural Fatty Acids Almost All Double Bonds have Cis Configuration Linear acids with Even Number Carbon Almost all Fatty acids Present in Mammalian Tissues are Aliphatic  Functions of EFA ( BioChemical Role ) 1 - Normal Growth 2 - Enter in Structure of Phosholipids & - Cholesterol Esters 3 - Formation of Prostaglandins & Leukotrienes Eicosanoids can be Derived from Arachidonic acid Precursor 4 - Structural Elements of Cell Membranes & Tissues. 6 - Maintain Integrity of reproductive system & Normal skin and Epithelium. 8 - Lower Serum Cholesterol Level ( Protective against Atherosclerosis & Coronary Heart Disease ) 9 – Excessive Intake of EFA can leads to * Increased CT & * Increased Fibrinolytic activity 11 – Deficiency of EFA can Produces * Fatty Liver & * Retinits Pigmentosa Properties of FA Physical Properties 1 – Solubility: Short chains FA are Soluble in Water Long chains FA are Insoluble in water ( Soluble in Non-Polar Solvents ) 2 – Melting Point: Depends on: - Chain Length of FA - Degree of Saturation Short chains & UnSaturated FA are Liquid at Room Temperature Long chains & Saturated FA are Solid at Room Temperature Animal Triacylglycerols ( Other than Fish ) Contain: 40 - 60% of Unsaturated Fatty Acids Fish: 75 – 80% Unsaturated & More PolyUnsaturated Plant Triacylglycerols: 85 – 90% Unsaturated Coconut: 92% Saturated Higher Content of UnSaturated Fatty acid Lower Melting Point Plant Triacylglycerol: Liquid at Room Temp.→ Oils Animal Triacylglycerol: Solid at Room Temp → fats Saturated FA Mono-Un-Saturated FA Poly-Un-Saturated FA  Chemical Properties Hydrogenation ( addition of Hydrogen ) Convert UnSaturated ( Yes = ) Into Saturated FA ( No = ) in the Presence of Heat & Nickel Halogenations ( addition of Hallogen e.g. Cl, F ) convert UnSaturated ( Yes = ) Into Saturated FA ( No = ) Oxidation ( addition of Oxygen ) Convert UnSaturated ( Yes = ) into Peroxide  Hydrogenation Margarine is Produced by Hardening of Vegetable Oils by Partial Hydrogenation into Semisolid or Solid Product Margarine considered Healthier than Butter Fatty acids with Trans Double Bonds have Physical Properties more like Saturated FA, also Raising Blood Cholesterol 2 – Salt (Soap) Formation: FA + Alkalies (e.g. Na hydroxide) Soap (Na salt) + H2O 3 – Ester Formation: FA + Alcohol Ester + H2O FA + Glycerol Neutral Fats (Triacylglycerol) FA + Higher alcohols Waxes  Classification of FAs I - Based on Saturation 1. Saturated: Single bonded - Palmitic acid. 2. Unsaturated: Double bonded – Oleic acid, linoleic acid, linolenic acid, arachidonic acid II - Based on Nutrition 1. Essential: Linoleic acid, Linolenic acid, Arachidonic acid. 2. Non essential: Remaining all other fatty acids.  III - Based on Length of Chain 1. Short Chain Fatty acids ( SCFA ) up to 8C atoms Butyric acid (4C), Caproic acid (6C) 2. Medium Chain Fatty acid ( MCFA ) 8-12 C atoms Caprylic acid (8C), Decanoic acid (10C) 3. Long chain Fatty acids ( LCFA ) > 12 C atoms Myristic acid (14C ) Palmitic acid (16C ) Stearic acid (18C ) 47  III - Based on Esterification 1. Esterified: ( 95% ) make Esters with Alcohols. Percentage of Esterification of Fatty acids is as follows: a. 45 % with Triglycerides. b. 35 % with Phospholipids. c. 15 % with Cholesterol. 2. Un-esterified: ( 5% )= Free TransPorted by albumin Plasma Level is 10-15 mg/dl  IV- Based on Isomerism 1. In case of Saturated FA a. Straight chain: Butyric acid. b. Branched: Isobutyric acid. 2. In case of Unsaturated FA a. Cis - Oleic acid b. Trans - Oleic acid 49  VI - Based on Number of Double Bonds 1. Monounsaturated ( MonoEthenoid, MonoEnoic ) One Double Bond e.g. Palmito-oleic acid, Oleic acid 2. Polyunsaturated ( PolyEthenoid, PolyEnoic ) 2 or more double bonds e.g. Linoleic & arachidonic 3. Eicosanoids: These are Derivatives of 20 C Polyenoic acids: Prostaglandins (PGs) Leukotriens (LTs) Prostacyclins (PCI) & Thromboxanesm (TXs)  VII - Based on Solubility Degree 1. Soluble: Short chain Fatty acids & Usually Polyunsaturated F.A 2. Insoluble: Long chain fatty acids Usually Saturated  VIII - Based on Melting Points 1. High Melting Point: Saturated Fatty Acids 2. Low Melting Point: Unsaturated Fatty Acids IX - Clinical Classification 1. Atherogenic: e.g. Saturated FA Cause atherosclerosis narrowing of BV 2. Atheroprotective: Prevent Atherosclerosis e.g. Polyunsaturated FA ( PUFA )  Saturated UnSaturated Fatty Acids Fatty Acids 1 - Single Bonds Double Bonds 2 - Less Abundant More Abundant 3 - Less Soluble More Soluble 4 - Melting Point High Melting Point Low 5 - May be Straight or May be Cis or Trans forms Branched 6. They are PolyUnSaturated are Non-Essential Essential  Saturated UnSaturated Fatty Acids Fatty Acids 7. Synthesized in Body Synthesized in Body Excluding the Essentials 8. Oxidized in the More Rapidly Oxidized in Body the Body 9. Elevate Cholesterol Lower Cholesterol Level. level 10. Don`t form Prostaglandins 20 Carbons Arachidonic acid forms & Leucotriens them.  Eicosanoids Are Cyclic Compounds that Derived from Arachidonic acid after its Cyclization ( 20 C Unsaturated with 4 Double Bonds ) Two Groups: 1 - Prostanoides 2 - Leukotrienes ( LT )  1- Prostanoides: A - ProstaGlandins (PG): - Their Types are A, B, D, E, F, G, H & I - have Hormonal Like Action - Can cause Vasodilation, Uterine & Intestinal Contraction B - ProstaCyclines - can Cause Vasodilation. - Inhibit Platelet Aggregation C- Thromboxans - can Cause Platelet Aggregation. 2 - Leukotrienes (LT) - Present in Leucocytes, Platelets & Mast Cells - Can Cause Chemotaxis (i.e. WBCs Collection at Site of inflamation) 59 Alcohols ( R.OH )  Alcohols Associated with Lipids Include: Glycerol, Cholesterol in Our Diet & Body But Higher alcohols are found in Wax  Glycerol - TriHydric Alcohol (Contain 3-OH groups) - Colorless, Odorless, - Hygroscopic & has Sweet Test - Souble in Water & Alcohols ( Not in Fat Solvents ) form Esters with FA Dehydration of Glycerol ( Removal two molecules of water in presence of conc. Sulphuric acid ) Leads to Acrolein Formation ( Aldehyde with Characteristic Odor ) Glycerol can be Used in Manufacuring of Cream & Lotions. used as a Drug ( Nitroglycerol ) for Coronary Dilation. Still in Simple Lipids Triacylglycerol Triacylglycerides makes ~90% of Our lipid diet All animal Fats and all Plant Oils O O OH C R1 H2C OH O H2C O C R1 O -3 H2O HC OH + OH C R2 HC O R2 O H2C OH H2C O R3 OH C R3 Glycerol Triacylglycerol O Fatty acids  Body Triacylglycerols TG are Stored mainly in Cytoplasm of Fat cells ( Located Subcutaniously, around Kidney & other Organs) Body Fat is Important Source of Energy ( i.e. Each Gram can give 9.3 Kcal ) Human Fat is Liquid at Room Temp. Dietary Sources Includes: Animal Sources; Butter, Lard Plant Sources; Oils as Cotton Seed, Linseed, Sesame & Olive Marine Oils; e.g. Cod Liver Oil, Shark Liver Oil - All TG are Water Insoluble (soluble in Fat solvents) - T.G. rich in Unsaturated FA are: Liquid at Room Temperature (Oils) - T.G. rich in Saturated FA are: Solid at Room Temperature (Fats) - T.G. Floats on Surface of Water so, its Specific Gravity < than 1 - All TG can Give +ve Grease Stain Test  Rancidity It is Toxic Reaction of T.G. Due to Oxidation of its Unsaturated FA by Oxygen of air, Bacteria or Moisture. Leads to Unpleasant Odor or Taste of oils & fats 3 Types : - Oxidative Rancidity - Ketonic Rancidity - Hydrolytic Rancidity Complex ( Conjugated ) or ( Compound ) Lipids  Are Esters of Fatty acids with Alcohol in addition to Other groups I - Phospholipids ( Subclassified into ) a GlyceroPhospho Lipids b SphingoPhospho Lipids II - Sphingolipids (may be with or without Phosphate) a Glycolipids b Sulfolipids c Gangliosides d Mucolipid II - Glycolipid IV - Proteolipids (Lipoprotein) 73 PhosphoLipids Types GlyceroPhosphoLipids e.g. Phosphotidic acid Lecithin Cephalin Plasmalogens Cardiolipin SphingoPhosphoLipids 74 e.g. SphingoMyelins  I- GlyceroPhosphoLipids: Phospholipids Containing Glycerol These contain Glycerol, Fatty acid, H3PO4 and in many cases a Nitrogenous base which may be Choline, Ethanolamine, Serine or Inositol e.g. Lecithins, Cephalins, Phosphatidic acid. Have Fatty acid Ester Groups at First Two Carbons of Glycerol At Third Carbon: PhosphoDiester Group 75  Glycero Phospho Lipids Phosphatidyl Choline Phosphatidyl Serine ( Lecithin ) Phosphatidic acid Phosphatidyl Ethanolamine Phosphatidyl Inositol ( Cephalin ) ( Lipositol ) 1- Phosphatidic acid: DiAcylGlycerol Phosphate the Parent & Precursor of All Other Types Formed of Glycerol Esterified at C1 (  ) with Saturated F.A at C2 (  ) with Unsaturated F.A at C3 (  ) with Phosphoric acid 2 - Cardiolipin: ( Di Phosphatidyl Glycerol ) Two Phosphatidic Acids Linked Together by Glycerol. Is the Major Lipid Mitochondrial Membrane It is Antigenic (Stimulate Antibody Formation) 3 - Phosphatidyl Choline ( Lecithin ) Phosphatidic acid + Choline Attached at Phosphoric acid at C3 () ( TriMethylated Decarboxylated Serine ) - Lecithin enter in Cell Membrane Structure - Lecithin act as Lipotropic Factor - Lecithin Can Form Cholesterol Ester (Transported to Liver to be Execreted into Bile) & Lysolythesin when React with Cholesterol by enzyme called LCAT & ACAT ACAT Lecithin + Cholesterol Cholesterol Ester + Lysolythesin LCAT Lecithin act as Store of Choline Cholin is Important for Nerve Transmission & Methyl Donor in Transmethylation Reactions Lecithin Prevent Cholesterol Gall Stones through Solublization of Cholesterol Di-Palmityl-Lecithin is Continuously Secreted by alveolar Cells of Lung to act as Lung Surfactant Prevent Lung Collapse (Adherence of Alveolar Wall) so, Help Expiration & Inspiration ( Makes Lung Easier to Expand ) Respiratory Distress Syndrome ( Hyaline Membrane Disease ) Occurred in Premature Babies where Lungs Not Secrete Enough Surfactant Leading to Lung Collapse & Respiratory Failure 4 - Phosphatidyl Ethanolamine ( Cephalin ): Phosphatidic acid + Ethanolamine ( Decarboxylated Serine ) One of Activating Factors of Coagulation Mechanism 5. LysoPhosphoLipids ( LysoLecithin & LysoCephalin ): Like Lecithins & Cephalins but i.e. Without FA in Position ( C2 =  ) which is Usually Unsaturated LysoLecithin is Important in Metabolism & InterConversion of Phospholipids LysoCephalin ( Strong Surface Acting Substance ) is used for Chocolate Manufacturing. 6. Phosphatidyl Serine: Phosphatidic acid + Serine (  amino,  hydroxy Propionate ) N.B. Threonine May be also Present 7 - Phosphatidyl Inositol: (Lipositol) Phosphatidic acid + Inositol (Alcohol Cyclic Sugar) Present in Cell Membrane, Precursor of 2nd Messenger Inositol Triphosphate ( Mediate Hormonal Action ) 8- Plasmalogen: as Lecithin But contain Unsaturated Alcohol attached to Glycerol at C1 ( Instead of Saturated FA ) Contribute about 10% of Phospholipids Present in Brain & Muscles 89  Glycerol Fatty acids Phosphatidic acid Glycerophospholipid O O O H2C OH OH C R 3 H2C O C R3 H2C O C R3 O O O -3 H2O HC OH + + OH C R 2 HC O C R 2 HC O C R2 O O O HOR1 H2C OH OH P OH H2C O P OH H2C O P OR1 - H2O O- O- O- Phosphoric acid Phosphodiester group  Decarboxylated Seine TriMethylated Ethanolamine α-Amino β-Hydroxy Propionate Cyclic Alcohol Sugar II- SphingoPhosphoLipids These contain Sphingosine (Higher alcohol Containing one OH group), Fatty acids, H3PO4 & Nitrogenous base ( Choline or Ethanolamine ) e.g. SphingoMyelins the Only Lipids that Contain Both Sphingosine & H3 PO4  SphingoMyelin: formed of Ceramide + Phosphoric acid + Choline i.e. Sphingosine + Fatty acid + Phosphoric acid + Choline ceramide  SphingoMyelins Present in High concentration in Brain & Nerve tissues Niemann Pick`s Disease due to Deficiency of Sphingomyelinase Enzyme Lead to Accumulation of Large Amounts of Sphingomyelin which Cause Mental retardation & Death in Early Life  Ceramide Not Phospholipids ( Parent Compound ) it is formed of Sphingosine + Fatty acid (Usually PUFA) ceramide  H 18 C alchohol HO C C CH(CH2)12CH3 H HC NH2 H2C OH 18 C Sphingosine alchohol  18 C alchohol 97  Function of Phospholipids occurred in Every Body Cell ( e.g. Brain, Muscles & Nerves ) Form Cell Membrane, Mitochondria & Golgi Important for Absorption of Lipids from intestine Important Component of Lipoproteins act as Lipotropic Factor ( Protect against Fatty Liver ) Phospholipids containing Cholin act as Methyl Donor in Transmethylation Reactions  Solubilize Cholesterol in Bile Acts as Signal Transmission across Cell Membranes Certain Enzymes require PL for their actions Play Role in Blood Coagulation Process Lecithin Lower Surface Tension & Emulsification in GIT. Have a Role in Transport of Lipids from Liver Have role in Electron Transport & Oxidative Phosphorylation 99  Sphingophospholipid SphingoPhosphoLipid & Sphingoglycolipid H H HO C C CH(CH2)12CH3 SphingoGlycoLipids HO C C CH(CH2)12CH3 H H O O H H HC N C R2 HC N C R2 O H2C O P OR1 CH2 CH2OH O- O O H Phosphodiester group H OH H CHO OH H H OH  SphingoLipids: These are NonPhosphate Containing 101 1 - Glycolipids: Contain Sphingosine, Fatty acid & Sugars ( Glucose or Galactose ) e.g. Cerebron, Nervon, Oxynervon, Kerasin, Mainly in White Matter of Brain & Myelin Sheaths. Include - Cerebrosides - Sulpholipids - Gangliosides - Ceramide oligosaccharides 102  Glycolipids Formed of : Ceramide ( Sphingosine + F.A. ) + Carbohydrate Types of Glycolipids: Sphingosine FA Cerebrosides: Ceramide + Single Galactose or Glucose Glucose or Galactose Sulfatides: CerebroSides Ceramide + Single Galactose + Sulfate Globosides: Ceramide + 2 or More Sugars. Gangliosides: Ceramide + oligosaccharide containing 1 or more sialic acid Simplest Ganglioside is Formed of: Ceramide + 1 Glucose + 1 Galactose + 1 Sialic acid Sphingosine F.A GanglioSides Glucose Galactose Sialic acid  Cerebrosides ( Simple Glycolipids ): Contain Sphingosine, Fatty acid & Sugar ( Glucose or Galactose ) Present in White Matter of Brain & Myelin Sheath of Nerve Fibers act as Insulators of Nerve Impluse 104  According to Type of FA, Cerebrosides can be Classified into Many Subtypes e.g. Kerasin; FA is Lignoceric acid ( C24 Saturated ) Cerebron; FA is Cerebronic acid ( C24 Hydroxy Sat. ) Nervon; FA is Nervonic acid ( C24 Unsaturated ώ9 ) Oxynervon; FA is Oxynervonic acid ( hydroxy Nervonic ) 105 2- Sulfolipids (Sulphatides) Are Cerebrosides Containing Sulphate group ( attached to Sugar ) Composed of Sphingosine, Fatty acid, Galactose & Sulfate group, Present Mainly in White Matter of Brain 106 3 - Gangliosides Complex Glycolipids because contain One or More Sialic acid Molecules in addition to hexose - Sphingosine, - Fatty acid, - 3 Molecules of Hexoses ( Glucose & Galactose ), - HexosAmine ( N-acetylHexosAmine ) & - Sialic acid ( One or More NANA ). 107  4 - Ceramide Oligosaccharides Contain - Sphingosine Base, - Fatty acid ( C24 ), - Many Glucose & Galactose units Present in Heart & Kidney 108  MucoLipids Resemble Gangliosides e.g. Globasides, Hematosides, Strandin. 109 Total Plasma Lipids ( 360 - 820 mg/dl ), Include; Triacylglycerol ( 80-180 mg/dl ), Phospholipids, Cholesterol ( Less than 220 mg/dl ), - Free Cholesterol ( 26-126 mg/dl ) - Esterified Cholesterol Free FA ( 6-16 mg/dl ), LipoProteins Lipid part & Protein part. Found in Cell Membrane, Mitochondria & Plasma Transport Insoluble Lipids between Blood & Different Tissues  Separated By Electrophoresis, Ultracentrifugation, Gas Liquid Chromatography & Thin Layer Chromatography By Electrophoresis: Separated into Chylomicrons Β-lipoproteins Pre Β-lipoproteins -lipoproteins By Ultracentrifugation: Separated into Chylomicrons Very low density lipoproteins ( VLDLs ) Low density lipoproteins ( LDLs ) High density lipoproteins ( HDLs )  Main Amount Amount of Types of Fraction Source Lipids of Lipids Apolipoprotein Apolipoprotein A, B48, C & E CM Intestine TG 98 % 2% VLDL Liver TG 90 % 10 % B100, C & E LDL From CholesterolCh 78 % 22 % B100 olesterol VLDL Ester & in blood phospholipids HDL Liver CholesterolCh 50 % 50 % A, C, D & E olesterol & Ester & intestine phospholipids FFA- Adipose FFA 1% 99 % Albumin Albumin tissue  Types, Source, Density, Size and Functions of Lipoproteins Fraction Source Density Size Function Chylo Transport of dietary TAG (mainly), Micron Intestine Lowest Largest cholesterol & cholesterol esters from the intestine to the tissues. VLDL Liver Transport of endogenous TAG from the liver to the peripheral tissues From Transport of cholesterol from the LDL VLDL liver to the peripheral tissues in blood Liver Transport of cholesterol from HDL & Highest Smallest peripheral tissues to the liver for intestine elimination FFA- Adipose Very Very Albumin tissue high small I. Based on Density: i. High Density Lipoproteins-- HDL ii. Low Density Lipoporteins--- LDL iii. Very Low Density Lipoproteins --- VLDL iv. Chylomicrons - lighter than water II. Based on Electrophoresis: i. Alpha - Lipoproteins--- ( HDL ) ii. Beta - Lipoproteins---- ( LDL ) iii. Prebeta - Lipoproteins -- ( VLDL ) iv. Chylomicrons - Stationary ( does not move ) III. Clinical Classification: i. Atherogenic : LDL, VLDL, Chylomicrons ii. Atheroprotective 117 : High density lipoproteins Derived Lipids  Derived Lipids Substances derived from Simple & Conjugated lipids By hydrolysis Include: 1 - Fatty acids ( Saturated & Unsaturated ) 2 - Glycerol 3 - Polycyclic Compounds as steroids. 4 - Carotenoids 5 - Ketone bodies 6 - Cholantherene Derived Lipids Hydrolytic Products: Monoglycerides, Glycerol, Fatty acids, Prostaglandins. Miscellaneous lipids Sterols, Cholesterol, Vitamins D,E,K & Steroids 120  Sterols & Steroids; Group of Compounds Contain Ring called Cyclopentano- Perhydro- Phenantherene Ring 121  Three six-membered & one five-membered rings Ring C Includes cholesterol, adrenocortical sexD Ring and hormones, and bile salts Ring A Ring B Cyclopentano-Perhydro-Phenantherene Ring Is Three Six-Membered & One Five-Membered Rings 123  Steroids have Steroid Nucleus Composed of 17 carbon atoms ( 4 Rings A, B, C, D ) & 2 Methyl Groups at C10 & C13 Making C18 & C19 Cyclopentano Perhydro Phenantherine Nucleus 18 18 19 19 Steroid Nucleus ( Ring ) Types of Sterols & Steroids - Cholesterol (Animal sterol) - Ergosterol (Plant sterol) - Vitamin D group (D2 & D3) - Bile Salts - Steroid Hormones ( Male & Female Sex hormones ) ( Adrenocortical Hormones ) - Digtalis Glycosides - Some Carcinogenic Substances 126  Steroids include: Sterols: Steroid alcohol for Example Cholesterol Bile acids: Primary bile acids & Secondary bile acids. Steroid hormones: Sex Hormones: Male sex hormones: e.g., Testosterone Female sex hormones: Estrogens & Progesterone Adrenocortical Hormones: Glucocorticoides as Cortisol, Cortisone & Corticosterone Mineralocorticoids as aldosterone Vitamins D Cholesterol ( 27C )  Cholesterol ( 27C ) is Formed of Steroid Nucleus, - OH group at C3 ( only polar group ), - 2 Methyl groups at C10 & C13 - One Double bond between C5 & C6 - 8 Hydrocarbon Side Chain at C17 Cyclopentano Perhydro Phenantherine Nucleus 18 19 Steroid Nucleus ( Ring )  Cholesterol is Present in Every Body Cell ( Cell Membranes ) Especially in; - Adrenal Cortex - Liver - Kidney - Brain & Nervous System - Skin  Occurs in Blood Either Esterified or Free Esterified with Long Chain FA to OH group at C3 Cholesterol may be of Exogenous ( Dietary ) or Endogenous ( formed Inside the Body ) Normal Plasma Level is Less than 220 mg/dl ( 5.3 mmol/ml ) High Cholesterol Levels Predispose to Atherosclerosis or Gall Bladder Stones  Steroid Nucleus, OH group at C3, One Double Bond between C5 & C6 & Long Side Chain at C17 - It is an Alchohol - Insoluble in Water ( Soluble in Fat Solvents ) - Form Characteristic Crystals with Broken Corner - Give Positive Lieberman Test ( Bluish Green Color ) - Present Only in Animals, Not in Plants  CopraStanol ( CoproSterol ) : Cholesterol in Intestine is Reduced ( Reduction of Double Bond Between C5 & C6 ) By Bacteria Flora Into Coprastanol Before its Excretion  FORMS OF CHOLESTEROL  Free Cholesterol: 30 %  Esterified Cholesterol: 70 % TRANSPORTATION BY:  LDL - Bad Cholesterol  HDL - Good Cholesterol Cholesterol Important in cardio- vascular disease → lower intake of cholesterol Critical to many physiological functions A component of membranes Precursor to all other animal steroids including adrenocortical & sex hormones, and bile salts Body synthesize cholesterol if it’s excluded from diet  Exogenous Butter, Cream & Milk & Milk Products Eggs, Especially Egg Yolk Beef, Meat ( Brain, Liver & Kidney ) Endogenous Synthesized in Tissues & Liver: I gm/day 140  Importance of Cholesterol Structure of cell membrane, brain, liver and other organs. Formation of Vitamin D. Precursor of steroid hormones. Gives bile salts by oxidation.  Biomedical Importance of Cholesterol Formation of: Bile acids Steroid Hormones Vit. D3 in Skin Lipoproteins Cell Membranes - Transport of Long chain FA - Has Insulating Effect in CNS - Makes Skin Highly Resistant to Absorb Water Soluble Substances - Prevents Water Evaporation from Skin Cholesterol Important in cardio- vascular disease → lower intake of cholesterol Critical to many physiological functions A component of membranes Precursor to all other animal steroids including adrenocortical & sex hormones, and bile salts Body synthesize cholesterol if it’s excluded from diet  Ergosterol Plant Sterol ( absorbed from Small Intestine ) Give Vitamin D2 by Ultraviolet Rays Similar to Cholesterol but Differ in - Extra Double Bond between C7 & C8 - Side Chain is Unsaturated & Has Extra Methyl group  Vitamin D Group Vitamin D2 Derived From Ergosterol By Rupture of Second Ring by Ultraviolet Rays Vitamin D3 Derived from 7-dehydrocholesterol By Rupture of Second Ring by Ultraviolet Rays  Bile Acids Are Hydroxy Derivatives of Cholanic acid ( C24 Steroid ) Two Types : 1 - Primary Bile Acids 2 - Secondary Bile Acids ( Not Containing OH at C7 )  1 - Primary Bile Acids - Cholic acid = 3, 7, 12 TriHydroxy Cholanic acid & - ChenodeoxyCholic acid = 3,7 Dihydroxy Cholanic acid formed in Liver during Cholesterol Catabolism 2 - Secondary Bile Acids ( Not Containing OH at C7 ) - DeoxyCholic acid = 3, 12 Dihydroxy Cholanic acid & - LithoCholic acid = 3 Monohydroxy Cholanic acid Formed By Action of Intestinal Bacterial 7 -dehydroxylase enzyme  Bile Salts: are Bile acids ( Cholic acids ) Conjugated with Glycine ( 80% ) & Taurine ( 20% ) Excreted in Bile from Liver in Form of: Na Salts of Glycocholate & Taurocholate Bile Salts in the Intestine Undergo Enterohepatic Circulation ( Reabsorbed from Intestine to Blood then Returned Back to the Liver to be Excreted Again in Bile )  Function of Bile Salts: Essential for - Digestion: Needed for Emulsification of Fat - Absorption: Participate in Micelle ( form of lipid during its absorption ) formation - Good way for Excretion of Cholesterol - Choleretic Effect: Enhance Liver to Excrete More Bile - Prevent Cholesterol Precipitation  Hormones of Steroid Nature “ Derived from Cholesterol ”  Female Sex Hormones Esrtogen: Three types: Estrone ( E1 ), Estradiol ( E2, most active ) & Estriol ( E3 ) Structure: - Ring A is unsaturated - OH at C3 - Methyl group at C13 * Ketone group at C17 (E1), * OH at C17 (E2) * 2 OH at C16, C17 (E2) Synthesis: From Cholesterol Site of Production: - Mainly: Ovary & Placenta in Female - Minor amounts: Adrenal cortex in both Male & Female Testis in Male Fate: E3 is the End product, Produced in the Liver & Conjugated with Sulphuric acid & Glucuronic acid then Excreted in Urine Biochemical Role of Estrogens - Stimulate development of Female Secondary Sex Characters e.g. Voice, Hair & Fat Distribution - Stimulate Development of Female Sex Organs e.g. Uterus - E2 has Anabolic Effects on Bone & Cartilages - Synthetic Estrogen can be Used for Contraception  Progestrone: Structure: * Ketone group at C3 * Double bond between C4 & C5 * Methyl group at C10 & C13 * Ketone ketone at C17 Site of Production: - Ovary & Placenta in female - Adrenal Cortex in Both Male & Female Fate: Pregnadiol is the End Product, Produced in the Liver & Conjugated with Sulphuric acid & Glucuronic acid then Excreted in Urine Biochemical Role of Progesterone: - Prepare Uterus for Implantation of the Ovum - Stabilizes Pregnancy ( Prevent Abortion ) - Stimulate Breast Acini during Puberty & Pregnancy - Inhibit Milk Production in Late Pregnancy After Delivery ( Progesterone Decreases Sharply & Cause Lactation ) - Adntagonizes Action of Estrogens at Various Tissues  Male Sex Hormones Androgens: Three Types: Testosterone, Dihydrotestosterone ( DHT ) Structure: - Ketone group at C3 - Double bond between C4 & C5 - 2 Methyl group at C10 & C13 - OH at C17 Dihydrotestosterone ( DHT ) ( active form in tissues ) has the Same Structure of Testosterone Without Double Bond Between C4 & C5  Androgens: Site of Production: - Interstitial cells of Leyding of the Testis in Male - Adrenal Cortex in Both Male & Female Fate: 17-Keto Steroids is the End Product ( Compounds having =O Instead of -OH at C17 e.g. Dehydro-Epiandrosterone Acetate (DHEA), Androsterone & Epiandrosterone ) Which is Excreted in Urine Biochemical role of Androgens: - Stimulate Development of Male Secondary Sex Characters e.g. Voice, Hair & Fat Distribution - Stimulate Sperm Formation ( Spermatogenesis ) - has Anabolic Effects on Proteins Variations in Urinary 17-keto Steroids Increased in Testicular Tumors & HyperCortisism ( Cushing syndrome ) Decreased in Hypogonadism & HypoCortisism ( Addison Disease ) Adrenal Cortical Hormones Three Types: Glucocorticoids & Mineralocorticoids Structure: - All have a ketone group at C3 - All have double bond between C4 & C5 - All have 2 Methyl group at C10 & C13 (except aldosterone) - All have a ketol group at C17 - Glucocorticoids have an - OH group or oxygen at C11 but Mineralocorticoids have No free OH group or Oxygen at C11  Adrenal Cortical Hormones: Site of Production: are Derived from Cholesterol in Adrenal Cortex of Suprarenal Gland Types: * Gluco-Corticoids: Corticosterone, Cortizol, Cortisone & 11-dehydrocorticosterone * Mineralo-Corticoids: Aldosterone, DeoxyCorticoSterone ( DOC ) Synthetic Derivative of DOC is called DeoxyCorticoSterone acetate (DOCA) used in treatment of addison disease ( hypocortissism )  Biochemical Role of Adrenal Cortical Hormones - GlucoCorticoids: Control Metabolism of CHO, Lipids & Proteins ( Have Anabolic Effect on CHO i.e. Anti-Insulin Effect ) ( have Catabolic Effect on Lipids & Proteins ) - MineralCorticoids: Control Metabolism of Minerals, Act Mainly on Kidneys where it promotes Secretion of K+ & H+ & Reabsorbtion of Na+ Lipid Peroxidation, Free Radicals, Antioxidants,  Free Radical is an Atom or Fragment of Molecule having One or More Unpaired Electron (it is Not Positively or Negatively Charged). So it is Very Reactive & Unstable. Free Radical will Steal Electron from another Molecule (e.g. in a cell wall) Creating a New One & a Chain reaction will Begins which leads to Cell damage.  Free Radicals can be Considered to be Partially Reduced Metabolites of Oxygen e.g. Superoxide Anion ( O-.2 ), Hydroxyl Radical ( OH-. ), H2O2 Peroxidation of Unsaturated FA Creates also Free Radicals. Sources of Free Radicals: A - Sources of Superoxide anion O-.2: 1 – Ischemia of Mitochondria 2 – Vascular Endothelium 3 – Circulating White Cells such as Neutrophils 4 – Conversion of Hypothanthin & Xanthin to Uric acid by Xanthin Oxidase  Sources of Free radicals: B - Peroxidation of Unsaturated FA Exposure of Lipids containing PUFA to Oxygen leads to Auto-oxidation = Peroxidation i.e. free radical formation Lipid Peroxidation is a Chain Reaction (i.e. Provide Continous Supply of Free Radicals which in Turn initiate Further Peroxidation & so on), initiation begins by Light or Metal ions. C- Other Sources of Free Radicals: 1 – Oxidation of Catecholamines 2 – Activated Neutrophils (produce free radicals to act as defense mechanism against bacteria) 3 – Reaction with Xenobiotic drugs through cytochrome P450 system of liver microsome. 4 – Cell ischemia in Myocardial Infarction 5 – Exposure to Sun Light & Osazone 6 – X-rays & -rayes Toxic effects of Free radicals: 1 – Cell damage due to rupture of cell membrane by free radicals produced by lipid (of cell membrane) Peroxidation 2 – AtheroScelerosis 3 – Malignancy (free radicals interact with DNA & other macromolecule leading to mutation & molecular damage)  4 – Aging process (in form of weakened immune system & some inflammatory diseases) 5 – Oxidation of - SH groups in protein (leads to loss of biological activity of some proteins & enzymes) 6 – Myocardial infarction (ischemic myocardial cells may produce free radicals Such as Superoxide O-.2, Hydroxyl Radicals OH-. & H2O2 which cause myocardial cell damage) Antioxidants & Prevention of Toxic effects of Free radicals: Antioxidants are substances (atoms) that can give up an electron to free radicals. So prevent their toxic effects. Through its conversion to normal atoms. 1- Artificial Antioxidants Types: Such as Propyl-gallate e.g. Butylated hydroxyanisol (BHA) & Butylated hydroxytoluene (BHT) Can be used as food additives 2- Natural Antioxidants: e.g. - Vitamin E - Vitamin C - B-carotenes - Some Enzymes (Peroxidase, Superoxide dismutase) Natural Antioxidants can be Classified into: A- Preventive natural antioxidants; reduce rate of chain initiation. They include: 1- Catalase (convert toxic hydrogen peroxide into water) 2- Peroxidase (convert toxic hydrogen peroxide into water) 3- Metal Chelators: (remove metals which may initiate FA peroxidation) A- Preventive natural antioxidants; reduce rate of chain initiation. They include: 1 - Catalase (Convert Toxic Hydrogen Peroxide into Water) Catalase 2H2O2 2H2O + O2 2 - Peroxidase (Convert Toxic Hydrogen Peroxide into Water) e.g. Glutathione Peroxidase (Need Selineum as Trace Mineral) glutathione peroxidase H2O2 + 2 GSH 2H2O + GSSG 3 - Metal Chelators: (Remove Metals which May initiate FA Peroxidation) e.g. EDTA (ethylenediamine tetraacetate), DTPA (diethylene triamine penta-acetate) B- Chain breaking natural antioxidants; interfere with chain propagation. They include: 1 - Superoxide Dismutase: (convert Superoxide Free radicals into Hydrogen Peroxide ) Superoxide Dismutase O-.2 H2O2 2- Vitamin E (Tochopherols): (break chain reaction through transfer a hydrogen atom of its phenolic group to peroxyl (ROO.) free radical of PUFA) 3 - Vitamin C : (It may react to regenerate Tochopherols. Also it may react with 2 molecules of peroxyl (ROO.) free radical converting them to non free radical products) 4 - Urate, Phenols & other amines End Of The Show