Lipids Module 7 PDF

Lipids Introduction to Lipids Introduction to Introduction to Lipids Lipids Introduction to Introduction to Lipids Lipi...

Lipids Introduction to Lipids Introduction to Introduction to Lipids Lipids Introduction to Introduction to Lipids Lipids Definition Biomedical Importance Lipids are a heterogeneous group of compounds related 1. High energy value of fats more by their physical rather than by their chemical 2. Essential fatty acids, fat-soluble vitamins and lipophilic properties. micronutrients are contained in fat of natural foods 3. Beneficial effects of long-chain ɷ3 fatty acids in They have the common property of being: cardiovascular disease, rheumatoid arthritis and 1. Relatively insoluble in water dementia 2. Soluble in nonpolar solvents such as ether, chloroform 4. Fats stored in adipose tissue serve as thermal insulator and benzene. Introduction to Introduction to Lipids Lipids  Biomedical Importance Classification Modification from Bloor McKee and McKee 5. Nonpolar lipids act as electrical insulators, allowing rapid Simple Lipids 1. Fatty acids and their derivatives propagation of depolarization waves along myelinated Fats 2. Triacylglycerols Waxes 3. Wax esters nerves Complex Lipids 4. Phospholipids 6. Lipids have essential roles in nutrition and health, and Phospholipids 5. Sphingolipids Glycosphingolipids or glycolipids knowledge of lipid biochemistry is essential for Other complex lipids (sulfolipids, aminolipids, 6. Isoprenoids understanding obesity, diabetes mellitus, and lipoproteins) Precursor and Derived Lipids atherosclerosis Fatty acids, glycerol, steroids, alcohols, fatty aldehydes, ketone bodies Introduction to Introduction to Lipids Lipids Carboxyl Group R Group = Long Hydrocarbon Chain Fatty Acids and Their Derivatives CH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2COOH Fatty Acids and Their Derivatives  ω γ β α SATURATED FATTY ACIDS CH3CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2CH2COOH The R group or long hydrocarbon chain has only single bonds 16 9 3 2 1 UNSATURATED FATTY ACIDS The R group or long hydrocarbon chain has at least one double CH3CH2CH2CH2CH2CH2CH=CHCH2CH2CH2CH2CH2CH2CH2COOH bond cis- vs trans- isomers MUFA, PUFA, eicosanoids ω γ β α Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives Common Name Systematic Name Abbreviation Structure Occurrence Lauric acid Dodecanoic acid 12:0 CH3(CH2)10COOH Spermaceti, cinnamon, palm, H H kernel, coconut oils, laurels, butter CH3CH2CH2CH2CH2CH2C=C-CH2CH2CH2CH2CH2CH2CH2COOH Myristic acid Tetradecanoic acid 14:0 CH3(CH2)12COOH Nutmeg, palm kernel, coconut oils, myrtles, butter Palmitic acid Hexadecanoic acid 16:0 CH3(CH2)14COOH Common in all animal and plant ω1 ω2 ω3 ω4 ω5 ω6 ω7 9 3 2 1 fats Stearic acid Octadecanoic acid 18:0 CH3(CH2)16COOH Common in all animal and plant fats IUPAC Name: cis-9-hexadecenoic acid Common Name: palmitoleic acid Arachidic acid Eicosanoic acid 20:0 CH3(CH2)18COOH Peanut oil Abbreviation: 16:1Δ9 Lignoceric acid Tetracosanoic acid 24:0 CH3(CH2)22COOH Cerebrosides, peanut oil Series: ω7 Cerotic acid Hexacosanoic acid 26:0 CH3(CH2)24COOH Beeswax, carnauba wax Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives  H H H H H H CH3CH2CH2CH2CH2CH2CH2CH2C=C-CH2CH2CH2CH2CH2CH2CH2COOH CH3CH2CH2CH2CH2C=C-CH2C=C-CH2CH2CH2CH2CH2CH2CH2COOH ω1 ω2 ω3 ω4 ω5 ω6 ω7 ω8 ω9 9 3 2 1 ω1 ω2 ω3 ω4 ω5 ω612 9 3 2 1 IUPAC Name: cis-9-octadecenoic acid IUPAC Name: all-cis-9,12-octadecadienoic acid Common Name: oleic acid Common Name: linoleic acid Abbreviation: 18:1Δ9 Abbreviation: 18:2Δ9,12 Series: ω9 Series: ω6 Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives H H H H H H H H H H H H H H CH3CH2C=C-CH2C=C-CH2C=C-CH2CH2CH2CH2CH2CH2CH2COOH CH3CH2CH2CH2CH2C=C-CH2C=C-CH2C=C-CH2C=C-CH2CH2CH2COOH ω1 ω2 ω3 15 12 9 3 2 1 ω1 ω2 ω3 ω4 ω5 ω6 14 11 8 5 3 2 1 IUPAC Name: all-cis-9,12,15-octadecatrienoic acid IUPAC Name: all-cis-5,8,11,14-eicosatetraenoic acid Common Name: α-linolenic acid Common Name: arachidonic acid Abbreviation: 18:3Δ9,12,15 Abbreviation: 20:4Δ5,8,11,14 Series: ω3 Series: ω6 Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives  Common Name Systematic Name Abbreviation Series Occurrence Palmitoleic acid cis-9-hexadecenoic acid 16:1 Δ9 ω7 In nearly all fats cis- or trans- geometric Oleic acid cis-9-octadecenoic acid 18:1 Δ9 ω9 Possibly the most common isomerism occurs in fatty acid in natural fats unsaturated fatty acids Linoleic acid all-cis-9,12-octadecadienoic acid 18:2Δ9,12 ω6 Corn, peanut, cottonseed, soybean, and many plant oils cis- if the acyl chains are on the α-linolenic acid all-cis-9,12,15-octadecatrienoic acid 18:3Δ9,12,15 ω3 Frequently found with same side of the double bond linoleic acid but particularly in linseed oil Arachidonic acid all-cis-5,8,11,14-eicosatetraenoic acid 20:4Δ5,8,11,14 ω6 Found in animal fats and in trans- if the acyl chains are on peanut oil; important component of the opposite side of the double phospholipids in animals bond Timnodonic acid all-cis-5,8,11,14,17-eicosapentaenoic 20:5Δ5,8,11,14,17 ω3 Important component of acid fish oils Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives Naturally occurring Melting points increase with unsaturated fatty acids are chain length and decrease nearly all cis-, the molecules according to unsaturation being “bent” 120 degrees at the double bond Membrane lipids are more unsaturated than storage lipids Increase in the number of cis- double bonds leads to various Tissue lipids subjected to spatial configurations of the cooling (hibernation) or in molecule, e.g. arachidonic acid extremities are more may have “kinks” or U-shape unsaturated Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives  Oleic acid H H CH3CH2CH2CH2CH2CH2CH2CH2C=C-CH2CH2CH2CH2CH2CH2CH2COOH H2 Hydrogenation Metal (nickel, Ni) HH CH3CH2CH2CH2CH2CH2CH2CH2C-C-CH2CH2CH2CH2CH2CH2CH2COOH Stearic acid HH Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives Oleic acid H H Lipid Peroxidation CH3CH2CH2CH2CH2CH2CH2CH2C=C-CH2CH2CH2CH2CH2CH2CH2COOH Initiation ROOH + metal (n)+ ROO + metal (n-1)+ + H+ X + RH R + XH Halogenation I2 Propagation R + O2 ROO ROO + RH ROOH + R HH Terminatio ROO + ROO ROOR + O2 CH3CH2CH2CH2CH2CH2CH2CH2C-C-CH2CH2CH2CH2CH2CH2CH2COOH n ROO + R ROOR 9,10-diiodo-octadecanoic acid I I R + R RR Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives  Lipid Peroxidation Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives Functions of Fatty Acids Influence on Biological Events As building blocks of phospholipids and glycolipids which are constituents of cellular membranes As fuel molecules As targeting molecules since fatty acids are attached to many proteins. In this way, proteins are directed to their appropriate places in membranes As messenger molecules since products of fatty acids function as hormones and as intracellular messenger molecules Fatty Acids and Their Fatty Acids and Their Derivatives Derivatives  Main storage form of fatty acids Esters of the alcohol GLYCEROL and 3 FATTY ACIDS Neutral fats Triacylglycerol Nearly all are mixed acylglycerols Fats versus oils Triacylglycero l When it is required to number the O O 1 carbon atoms of glycerol, the –sn- H2 C OH CH3CH2(CH2)12CH2 C OH H2 C O C CH2(CH2)12CH2CH3 H2 C OH (stereochemical numbering) system is H H O O H H 2 used. HC OH + CH3(CH2)7C=C-(CH2)7 C OH HC O C (CH2)7C=C-(CH2)7CH3 HC OH For example, if carbons 1 and 3 of O O glycerol are esterified to stearic acid and H2 C OH CH3CH2(CH2)14CH2 C OH H2 C O C CH2(CH2)14CH2CH3 H2 C OH carbon 2 is esterified to palmitic acid, then the resulting triacylglycerol would Glycerol 3 Fatty acids 1-palmityl-2-oleoyl-3-stearyl-sn-glycerol 3 be named as 1,3-distearyl-2-palmityl-sn-glycerol + 3H2O Triacylglycero Triacylglycero l l  Functions of Triacylglycerols Major storage and transport form of fatty acids Store energy more efficiently than glycogen for several reasons Because they are hydrophobic, triacylglycerols coalesce into compact anhydrous droplets within cells TAGs are less oxidized than carbohydrate molecules (9.3 kcal per gram of fat versus Phospholipids 4.1 kcal per gram of carbohydrate) Provide insulation in low temperatures Triacylglycero l There are two types of phospholipids Phosphoglycerides The most numerous phospholipid molecules found in cell membranes Phosphoglycerides contain glycerol, 2 fatty acids, Phosphatidic acid is the simplest phosphoglyceride and the precursor for all phosphate and an alcohol other phosphoglyceride molecules The most common fatty acids in the phosphoglycerides have between 16 and 20 Sphingomyelin differ from phosphoglycerides in that they carbons. Saturated fatty acids usually occur at C-1 of glycerol (sn-1) and the contain sphingosine instead of glycerol, 1 fatty acid, fatty acid substituent at C-2 (sn-2) of glycerol is usually unsaturated phosphate and an alcohol called choline Phosphoglycerides are classified according to which alcohol becomes esterified to the phosphate group Phospholipids Phospholipids  O H2 C O C CH2(CH2)12CH2CH3 O O O H H H2 C O C CH2(CH2)12CH2CH3 H2 C O C CH2(CH2)12CH2CH3 HC O C (CH2)7C=C-(CH2)7CH3 O H H O H H (CH2)7C=C-(CH2)7CH3 O HC O C (CH2)7C=C-(CH2)7CH3 HC O C H2 C O P O XH X is –H from H2O O O O- H2 C O C CH2(CH2)14CH2CH3 H2 C O P O X O- Phosphatidic acid Triacylglycerol Phosphoglyceride Simplest phosphoglyceride Precursor of all other phosphoglycerides Phospholipids Phospholipids O O H2 C O C CH2(CH2)12CH2CH3 H2 C O C CH2(CH2)12CH2CH3 O H H O H H HC O C (CH2)7C=C-(CH2)7CH3 HC O C (CH2)7C=C-(CH2)7CH3 O CH3 O H H2 C O P O XCH2CH2N+ CH3 X is from choline H2 C O P O XCH2CH2N+ H X is from ethanolamine O- CH3 O- H Phosphatidylcholine (lecithin) Phosphatidylethanolamine (cephalin) Most abundant phospholipids in cell membranes Found also in cell membranes Represent large proportion of the body’s store of choline Play a role in membrane fusion and regulation of membrane curvature Dipalmitoylphosphatidylcholine is a major component of surfactant 45% of phospholipids in nervous tissue Phospholipids Phospholipids  O O H2 C O C CH2(CH2)12CH2CH3 H2 C O C CH2(CH2)12CH2CH3 O H H O H H HC O C (CH2)7C=C-(CH2)7CH3 HC O C (CH2)7C=C-(CH2)7CH3 O H O H + H2 C O P O XCH2C-NH3 X is from serine H2 C O P O XCH2C-CH2OH X is from glycerol O- COO- O- OH Phosphatidylserine Phosphatidylglycerol Important cell membrane component which plays a It is one of the phosphoglycerides found in pulmonary surfactant key role in cell cycle signaling, specifically in relationship to apoptosis Phospholipids Phospholipids O O O H2 C O C CH2(CH2)12CH2CH3 H2 C O C CH2(CH2)12CH2CH3 H2 C O C CH2(CH2)12CH2CH3 O H H O H H O H H HC O C (CH2)7C=C-(CH2)7CH3 HC O C (CH2)7C=C-(CH2)7CH3 HC O C (CH2)7C=C-(CH2)7CH3 OH OH O H O O H H2 C O P O XCH2C-CH2 O P O CH2 H2 C O P O XH H X is from myoinositol H HO O- OH O- X is from O- H OH phosphatidylglycerol OH H Diphosphatidylglycerol (cardiolipin) Phosphatidylinositol Phospholipid abundant in mitochondria where it helps It is a precursor of second messengers build quaternary structures of Complex III and Complex IV Phosphatidylinositol 4,5-bisphosphate is an important component of cell membrane Plays a role in triggering apoptosis phospholipids; upon stimulation of suitable agonist, it’s cleaved into DAG and ITP 3 Phospholipids Phospholipids  Ceramide (Sphingosine + Fatty acid) Sphingosine Fatty acid = Palmitic acid Sphingomyelin OH HO Although found in most animal cell membranes, sphingomyelins are found in large quantities in brain and nerve tissue CH3-(CH2)12-CH=CH-CH-CH-N-C-(CH2)14-CH3 CH2 O On hydrolysis, sphingomyelin yields a fatty acid, phosphoric acid, choline and a Phosphoric acid O P O- CH3 complex amino alcohol called sphingosine. THERE IS NO GLYCEROL. O CH2CH2N+ CH3 Choline CH3 The combination of sphingosine plus fatty acid is known as a ceramide. Sphingomyelin Phospholipids Phospholipids Properties of Phospholipids Properties of Phospholipids Amphipathic molecules; all phospholipids have hydrophobic and hydrophilic When suspended in water, PL spontaneously rearrange into ordered structures domains The phospholipid hydrophobic groups are buried in the interior to exclude Hydrophobic domain is composed largely of the hydrocarbon chains of fatty water while the hydrophilic polar head groups are oriented so that they are acids exposed to water Hydrophilic domain, called polar head group, contains phosphate and other When in sufficient concentration, phospholipids form bimolecular layers. This charged or polar groups property is the basis of membrane structure. Phospholipids Phospholipids  Sphingolipids Phospholipids Important component of animal and plant membranes The major types of sphingolipids are the following Contain a long chain amino alcohol. In animals, this Sphingomyelin (also a phospholipid) – presence of a alcohol is primarily sphingosine while in plants, it is phosphate group phytosphingosine Glycosphingolipids or glycolipids – absence of a Ceramide is the core of each type of sphingolipid, a fatty phosphate group but replaced with a monosaccharide, acid amide derivative of sphingosine disaccharide or oligosaccharide. Sphingolipids Sphingolipids  OH OH OH + CH3(CH2)12CH=CH-CH-CH-NH3 + CH3(CH2)12CH2CHCH-CH-NH3 Glycosphingolipids CH2OH CH2OH Glycolipids are widely distributed in every tissue of the body particularly in nervous tissue such as brain Sphingosine Phytosphingosine Monosaccharide, disaccharide or oligosaccharide is attached to a ceramide Sphingosine Fatty acid through an O-glycosidic linkage OH HO CH3(CH2)12CH=CH-CH-CH-N-C-(CH2)14CH3 Most important classes include cerebrosides, sulfatides and gangliosides CH2OH Ceramide Sphingolipids Sphingolipids Glycosphingolipids Glycosphingolipids Cerebrosides are sphingolipids in which the head group is a monosaccharide. Sphingolipids that possess oligosaccharide groups with one or more sialic acid residues are called gangliosides Galactocerebroside, the most common, are almost entirely found in the cell membranes of the brain. Glucocerebroside is the predominant The names of gangliosides include subscript letter and numbers where the glycosphingolipid in extraneural tissues but occurs in small amounts in the brain letters M, D, and T indicate whether it contains one, two, or three sialic acid residues, and where the numbers designate the sequence of sugars attached to ceramide If a cerebroside is sulfated (SO3- or SO42-), it is referred to as a sulfatide. Sulfatides are negatively charged in physiological. Sulfogalactosylceramide or galactocerebroside sulfate is present in high amounts in myelin Sphingolipids Sphingolipids  Sphingomyelin Galactocerebroside (if R=H) Galactocerebroside sulfate (if R= SO3-) Sphingolipids Sphingolipids Selected Sphingolipid Storage Diseases Disease Manifestations Accumulating Enzyme Deficiency Sphingolipid Tay-Sachs disease Blindness, muscle Ganglioside GM2 β-Hexosaminidase A weakness, seizures, mental retardation Gaucher’s disease Mental retardation, liver and spleen enlargement, erosion Glucocerebroside β-Glucosidase Isoprenoids of long bones Krabbe’s disease Demyelination, Galactocerebroside β-Galactosidase mental retardation Niemann-Pick disease Mental retardation Sphingomyelin Sphingomyelinase Sphingolipids  Isoprenoids are biomolecules that contain repeating Terpenes five-carbon structural units known as isoprene units Found largely in the essential oils of plants Consist of terpenes and steroids Classified according to the number of isoprene residues they contain Monoterpenes are composed of two isoprene units (e.g. geraniol in oil of C CH3 CH3 O O geranium) C-C=C-C CH2=C-CH=CH2 CH2=C-CH2CH2 O P O P O- O- O- CH2OH Isoprene unit Isoprene Isopentenyl pyrophosphate Isoprenoids Isoprenoids Terpenes Terpenes Sesquiterpenes are composed of three isoprene units (e.g. farnesene which is Diterpenes are composed of four isoprene units (e.g. phytol which is a plant an important constituent of oil of citronella, a substance used in soap and alcohol) perfumes) CH2OH Farnesene Phytol Isoprenoids Isoprenoids  Terpenes Terpenes Triterpenes are composed of six isoprene units. Squalene, which is found in Tetraterpenes are composed of eight isoprene units. Carotenoids, the large quantities in shark liver oil as well as olive oil and yeast, is a good example. orange-colored pigments found in most plants, are the only tetraterpenes. Squalene is an intermediate in the synthesis of steroids Xanthophylls are oxygenated derivatives of this group Squalene β-Carotene Isoprenoids Isoprenoids Terpenes Terpenes Polyterpenes are high-molecular-weight molecules composed of hundreds or Mixed terpenoids are biomolecules composed of nonterpene components thousands of isoprene units. Natural rubber is a polyterpene composed of attached to isoprenoid groups. Examples include vitamin E (α-tocopherol), between 3000 and 6000 isoprene units ubiquinone, and vitamin K CH2-C=CH-CH2 CH3 n Natural Rubber α-tocopherol Isoprenoids Isoprenoids  Steroids Steroids are complex derivatives of triterpenes Each type of steroid is composed of four fused rings. The resulting structure is called the cyclopentanoperhydrophenanthrene ring or the steroid nucleus Isoprenoids Isoprenoids Steroids Steroids It is important to realize that in structural formulas of steroids, a simple Steroids are distinguished from each other by the placement of carbon-carbon hexagonal ring denotes a completely saturated six-carbon ring with all valences double bonds and various substituents (e.g. hydroxyl, carbonyl, and alkyl satisfied by hydrogen bonds unless shown otherwise; i.e. IT IS NOT A BENZENE groups) RING If the compound has one or more hydroxyl groups and no carbonyl or carboxyl Methyl side chains are shown as single bonds unattached at the farther (methyl) groups, it is called a sterol, and the name terminates in –ol end. These occur typically at positions 10 and 13 (constituting C atoms 18 and 19). Cholesterol is probably the best known steroid because of its association with atherosclerosis. However, aside from being an essential component of cell A side chain at position 17 is usual (as in cholesterol) membranes, it is a precursor in the biosynthesis of all steroid hormones, vitamin D, and bile salts or acids Isoprenoids Isoprenoids  Cholesterol is usually stored in cells as a fatty acid ester (cholesteryl ester), catalyzed by the enzyme acyl CoA:cholesterol acyltransferase, which is located in the cytoplasmic face of the endoplasmic reticulum Cholesterol 3-hydroxy-5,6-cholestene Isoprenoids Isoprenoids Progesterone Testosteron Aldosterone Cortisol e 17-β-Estradiol Cholic acid Isoprenoids Isoprenoids  Lipoproteins Cardiac glycoside: Digitoxin Isoprenoids Lipoprotein can describe any protein covalently linked to The protein components of lipoproteins are called lipid groups, but it is most often used for a group of apolipoproteins or apoproteins molecular complexes found in blood plasma of mammals Lipoproteins are classified according to their densities Plasma lipoproteins transport lipid molecules through the bloodstream from one organ to another Chylomicrons, which are large lipoproteins of extremely low density, transport dietary triacylglycerols and Also contain lipid-soluble antioxidants such as cholesteryl esters from intestine to tissues especially α-tocopherol and several carotenoids muscle and adipose tissues Lipoproteins Lipoproteins  Very low density lipoproteins (VLDL) are synthesized in High density lipoproteins (HDL) are also produced in the the liver and they transport lipids to tissues liver and play a role in scavenging of excessive cholesterol from cell membranes Low density lipoproteins (LDL) transport cholesterol to tissues. As VLDL are transported through the body, they HDL transport cholesteryl esters formed when the enzyme become depleted of TAG, as well as some apoproteins and lecithin:cholesterol acyltransferase (LCAT) transfers a fatty PL. Eventually, VLDL are converted to LDL acid residue from lecithin to the liver for bile acid synthesis Lipoproteins Lipoproteins End of Presentation Thank You Lipoproteins