VI. Complex lipids: 1. Phospholipids (PL): A. Glycerophospholipids. e Glycerol backbone. e Essential for membrane structure. ¢ Most abundant membrane lipids. 1. Carbons 1 & 3 of glycerol are not identical: It is important to realize that carbons 1 and 3 of glycerol are not identical when viewed in three dimensions pro-S position ————> H,0—OH 1 | 1 HO m2; a} | pro-R position ———> HSC —OH pro-chiral center Glycerol.Enzymes readily distinguish between them and are specific for one or the other carbon; e.g., glycerol is always phosphorylated on sn-3 by glycerol kinase to give glycerol 3-phosphate and not glycerol 1- phosphate. pro-S position CH,OH CH,OPO- no—b—n = | pro-R position ————* CH,OPO}- CH,OH -Glycerol-3-phosphiate p-Glyceroll phosphate, eT sn-Glycerol-3-phosphate e (D,L) system of nomenclature can be ambiguous for molecules with two or more chiral centers. e The (R,S ) system of nomenclature are more versatile system that naming each of several chiral centers in a molecule, priorities are assigned to each atoms in groups with higher atomic numbers. e R (Latin rectus, "right", clockwise) e S (Latin sinister, "left", counterclockwise) e To number the carbon atoms of glycerol clearly, the -sn- (stereochemical numbering) system is used, in which C-1 is, by definition, that group of the prochiral compound that occupies the pro-S position. The common form of glycerol phosphate in phospholipids is, by this system, sn-glycerol 3-phosphate.2. General structure: Glycerophospholipids may be regarded as derivatives of phosphatidic acid, in which the phosphate is esterified with the - OH in a C3 of glycerol molecule as a polar head and two fatty acids in a C1 and C2 as a nonpolar tails, 0 I Saturated fatty acid (-0-"Ch =—?} ss teammniieasa — /\/A\AA/)AV/ SF tei gos { me fophotic groups Unsoturatd fatty acid (0-H tea,dtieadd) \/\/\ AS AAV | ( 1 ‘CH-0-P-0-X baton General stuture of Cysrophosppd(Phospate acid) ‘nthe, Schematic Structure of a PhospholipidThe X maybe; Name of Not change Mycorephosphelipid Name of Formula of X Gt pit Phesphatidis acid —H Phoaphatidslethanolamine Rehanlamine — on —cH itt, ° (Cephatiny Phoophatidylcholine(Lecithin) Choline CH, —CH—NICHy)y Phoaphatidslecrine Serine cH ortn, a 00" Phoephatidyglycers Glycerol = a, cHcH on a a 2 Phosphatidslinositol myo-Inositol 45 uw - ‘4e-bispheaphate ‘bisphosphate > I —P Hou Diphosphavidvlatycerat Phoephatidy!- on -2 (Cordelipie) seers fro ° Oa Hy . | ° nob ° y—-O—0—R? If X is; a. Ethanolamine; the molecule is called phosphotidylethanolamine (Cephalin). « Exists in brain tissue and also. e Participates in blood clotting. b. choline; the molecule is called phosphotidylcholine (Lecithin). e The most abundant phospholipids of the cell membrane e Exists in brain, neural tissue, and in eggs. e Play an important role in reducing surface tension of the moist inner surface of the alveoli. e Its absence from the lungs of premature infants causes respiratory distress syndrome.. Inositol; the molecule is called Phosphatidylinositol 4,5- bisphosphate. e It is an important constituent of cell membrane phospholipids. e When stimulation by a suitable hormone agonist, it is cleaved into diacylglycerol (DAG) and _ inositol trisphosphate (IP3), both of which act as internal signals or second messengers. . Lysophospholipids: These are phosphoacylglycerols containing only one acyl radical, eg, lysophosphatidylcholine (lysolecithin), Important in the metabolism and_ interconversion of phospholipids. It is also found in oxidized lipoproteins and has been implicated in some _ of their effects in promoting atherosclerosis. Choline Lysophosphatidylcholine (lysolecithin).. Plasmalogens: These compounds constitute as much as 10% of the phospholipids of brain and muscle. Structurally, the plasmalogens resemble phosphatidyl- ethanolamine but possess an ether link on the sn-1 carbon instead of the ester link found in acylglycerols. Typically, the alkyl radical is an unsaturated alcohol. In some instances, choline, serine, or inositol may be substituted for ethanolamine a Ethanolamine Plasmalogen. B. Sphingolipids. * Sphingosine, fatty acid and glycoside. « Component of a certain membrane.1. General structure: Sphingolipids; Also have a polar head group and two nonpolar tails. They are composed of one molecule of the long-chain amino alcohol sphingosine (also called 4-sphingenine) or one of its derivatives, one molecule of a long-chain fatty acid, and a polar head group that is joined by a glycosidic linkage in some cases and by a phosphodiester in others. Carbons C-1, C-2, and C-3 of the sphingosine molecule are structurally analogous to the three carbons of glycerol in glycerophospholipids. Sphingosine HO—CH—CH=CH—(CH,).—CH, Fatty General structure of Sphingolipid The X maybe; I Sphingomyelin Phosphocholine = — f-O—CH—CHly-NCHh b If X is; phosphocholine: the molecule is called sphingomyelin that found in large quantities in brain and nerve tissue.2. Glycolipids: ¢ Glycolipids are widely distributed in every tissue, particularly in nervous tissue such as brain eThey occur particularly in the outer leaflet of the plasma membrane, where they contribute to cell surface carbohydrates. eThe major glycolipids found in animal tissues are glycosphingolipids. A. Glycosphingolipids: They contain ceramide and one or more sugars. The X sugar maybe; Neutral glycolipids Wt Glucosyicerebroside Glucose mi Lactosylceramide Di, tri-, or (a globoside) tetrasaccharide Complex Ganglioside GM2 “oligosaccharide (a) = Gal1. Galactosylceramide: elt is a major glycosphingolipid of brain and other nervous tissue. elt contains a number of characteristic C24 fatty acids, eg, cerebronic acid (-OH group in C2). eGalactosylceramide can be converted to sulfogalactosylceramide (sulfatide), present in high amounts in myelin. 2. Glucosylceramide: It is the predominant simple glycosphingolipid of extraneural tissues, also occurring in the brain in small amounts 3. Gangliosides: e They are complex glycosphingolipids derived from glucosylceramide that contain in addition one or more molecules of a sialic acid. e Neuraminic acid (NeuAc), is the principal sialic acid found in human tissues. e Gangliosides are also present in nervous tissues in high concentration. e They appear to have receptor and other functions.B. Galactolipids (sulfolipids): Predominate in plant cells. They contain two fatty acids esterified to glycerol and one or two galactose residues are connected by a glycosidic linkage to C-3 of a 1,2- diacylglycerol, but lack the characteristic phosphate of phospholipids. Storage ‘Membrane lipids (polar) lipids (neutral) Phospholipids Glycolipid i Triacylglycerols Glycerophospholipids Sphingolipids Sphingolipids Galactolipids (sulfolipids) Yea re] Mono-or ian Glycerol Sphingosine Sphingosine Glycerol Glycerol Po, {ateta] | Hfpo.- foie] | Fg] | Fer]3. Lipoproteins: ¢ They are a group of molecular complexes found in the blood plasma of mammals. « Plasma lipoproteins transport _lipid molecules (Triacylglycerols, phospholipids, and cholesterol) through the blood stream from one organ to another. ¢ The protein components of lipoproteins are called apo- lipoproteins or apo-proteins. A. Lipoprotein particle contents. 4. Inner core - hydrophobic. sro ‘ _ shox a. Cholesterol esters. driest b. Triglycerides. \f 2. Outer surface - amphipathic. a. Amphipathic phospholipids. b.Free cholesterol. LIS > test esters apopotcin c. Apoproteins.B. Classification of lipoproteins; depends on their density; 1. Chylomicrons - large lipoproteins, low density, formed in the mucosal cells of intestine, used in transport of dietary triglycerides and cholesterol ester from intestine to tissues. 2. VLDL — synthesized in the liver, responsible for transport of lipids to the tissues, triglyceride rich. 3. IDL — triglycerides and cholesterol. 4.LDL - they are products of VLDL, they carry cholesterol to the tissues to be used for the synthesis of cell membranes, steroid hormones, and bile saltes. Note: When the level of LDL exceeds the amount of cholesterol needed by the tissues, the LDLs deposit cholesterol to the arteries, which can restrict blood flow and increase the risk of developing heart disease and for myocardial infarctions (heart attacks). This is why LDL cholesterol is called "bad" cholesterol5.HDL — produced in the liver, remove excess cholesterol from the tissues and carry it to the liver where it is converted to bile salts and eliminated. Note: When HDL levels are high, cholesterol that is not needed by the tissues is carried to the liver for elimination rather than deposited in the arteries, which gives the HDLs the name of "good" cholesterol. Because high cholesterol levels associated with the onset of arteriosclerosis and heart disease, the serum levels of LDL and HDL are generally determined in a medical examination. For adults, recommended levels for; Total cholesterol< 200mg/dl. LDL< 130 mg/dl. HDL > 40 mh/dl A lower level of serum cholesterol decreases the risk of heart disease, Higher HDL levels are found in people who exercise regularly and eat less saturated fat.VIl.Precursor and derived lipids: 1, Terpenes: e The terpenes are a class of lipids formed from combinations of two or more molecules of 2-methyl-1,3-butadiene, better known as isoprene (abbreviated C5). Head-to-tail Tail4o-tail linkage. CHg se 7 p< C. @ nyc? Neu, Isoprene Geraniol « lsoprene units can be linked in terpenes to form straight chain or cyclic molecules, and the usual method of linking isoprene units is head to tail. e Monoterpene (C10) consists of two isoprene units that occur in all higher plants. Many of the large number of monoterpenes identified in plants have characteristic odors or flavors. E.g., limonene and a-pinene are the major components of lemon oil and turpentine, eS Limonene o-Pinene respectively.Sesquiterpene (C15) consists of three isoprene units Diterpene (C20) has four isoprene units, and so on. Triterpenes are C30 terpenes and include squalene and lanosterol, two of the precursors of cholesterol and other steroids Tetraterpenes (C40) are less common but include the carotenoids, a class of colorful photosynthetic pigments, e.g., 8-Carotene is the precursor of vitamin A, while lycopene, similar to B- carotene but lacking the cyclopentene rings, is a pigment found in tomatoes. . Steroids: e A cyclic compound of animal or plant origin, the basic nucleus of which consists of three 6-membered rings resembling phenanthrene (rings A, B, and C) and one 5- membered ring (ring D), fused together to yield perhydrocyclopentanophenanthrene e The steroids represent a wide variety of compounds, including sterols, bile acids, adrenocortical hormones, and sex hormones.A.Sterol: A steroid in which an alcoholic hydroxyl group is attached to position 3, and an aliphatic side chain of eight or more carbon atoms is attached to position 17 of the steroid nucleus; a steroid alcohol. 1. Cholesterol: e Is one of the most important and abundant steroids in the body. e Steroid is based on a core structure of sterol. e Itwas first isolated from gall stones. e Rich sources of cholesterol are; brain, nervous tissues, adrenal glands, egg yolk. e |thas a molecular formula (C27H4sOH). 21. 30 22 23 26 24 16 25 27 15 4 5 Cholesterola. Roles of cholesterol in mammals: 1. Structural component of plasma membrane and modulates membrane fluidity, 2. Precursor of steroid hormones and bile acids. b. Properties of cholesterol: 1. It is present in blood to the extent 150-250mg/L. 2.Cholesterol is a white crystalline substance showing the usual solubility properties of the lipids 3. It has a melting point of 149°. 4. It is usually prepared in laboratory by extraction from brain or spinal cord with acetone. 5. It is a poor conductor of electricity and functions probably as an insulating mechanism for the nerve impulses 6.Cholesterol is considered as a precursor of bile salts, steroid hormones, and vitamin D3.c. Color reactions: 1. Salkowski reaction: ¢ when a solution of cholesterol in chloroform is shaken with an equal volume of concentrated H2SO,4 and the layers are allowed to separate e The chloroform layer is red. e The acid layer is greenish fluorescence. 2. Liberman-Burchard reaction: e To a solution of cholesterol in chloroform a few drops each of acetic * Anhydride + concentrated H2SO, give a rose color, then rapidly changes to blue and finally to green. d. Cholesterol in the body: 1.Cholesterol is a component of a cell membranes, myelin sheath, brain, and nerve tissue. 2.It is also found in the liver, bile salts, and skin, where it forms vitamin D. 3.It is used to synthesize steroid hormones in the adrenal gland 4. Most of the cholesterol in the body is synthesized in the liver from fats, carbohydrate, and proteins, although some comes from the diet (meats, milk, and eggs). However, a person on a high- fat diet reabsorbs cholesterol from the bile salts causing less cholesterol to be eliminated 5.1n addition, higher levels of saturated fats stimulate the synthesis of cholesterol by the liver. 6. There is no cholesterol in vegetable and plant productse. Cholesterol levels: 1. If the diet is high in cholesterol, the liver produces less. 2.A typical daily American diet includes 400-500mg of cholesterol, one of the highest in the world 3. The American heart Association has recommended that we consume no more than 300 mg of cholesterol of a day. 4.When cholesterol exceeds its saturation level in the bile, gallstone may be form. 5. Gallstones are composed of almost 100% cholesterol with some calcium salts, fatty acids, and phospholipids 6.High levels of cholesterol are also associated with the accumulation of lipid deposit (plaque) that line and narrow the coronary arteries. 7. Clinically, cholesterol levels are considered elevated if the total plasma cholesterol level exceeds 200-220 mg/dl 8. Some research indicates that saturated fats in the diet may stimulate the production of cholesterol by the liver. 9.A diet that is low in foods containing cholesterol and saturated fats appears to be helpful in reducing the serum cholesterol level. 10.Other factors that may also increase the risk of heart disease are; Family history. Lack of exercise. Smoking Obesity. Diabetes Gender. Age.2. Ergosterol e Ergosterol occurs in plants and yeast and is important as a precursor of vitamin D jen Ergosterol. e When irradiated with ultraviolet light, it acquires antirachitic properties consequent to the opening of ring B. B.Bile salts: « The bile salts are synthesized in the liver from cholesterol and stored in the gallbladder. ¢ When bile is secreted into the small intestine, the bile salts mix with the water-insoluble fats and oils in our diets. e The bile salts act like soap, breaking a part and emulsifying large globules of fat. « The emulsions that form have a large surface area for the lipases, enzymes that digest fat.e The bile salts also help in the absorption of cholesterol into the intestinal mucosa e If large amounts of cholesterol accumulate in the gallbladder, cholesterol can precipitate out and form gallstones. e If gallstones pass into the bile duct, the pain can be severe. e Ifthe gallstone obstructs the duct, bile cannot be excreted e Then bile pigments known as bilirubin enter the blood where they cause jaundice, which gives a yellow color to the skin and eyes. VIII. Biological membranes: The major function of phosphorus-containing lipids in living systems is to form biological membranes. 1. The biological membranes functions: Indispensable of life. « Barriers the separates living systems into various regions. e Membrane separate cells from their surrounding. e Semi permeable. ¢ Control the flow of information.. Properties of biological membranes: Most membranes contain 40% lipids and 60% proteins, but there is considerable variation in these amounts, depending on the particular cell. Certain molecules can pass through selective membrane, e.g. the nutrients of a cell and its waste product pass through the membranes. Other compounds are not allowed to pass A semi permeable membrane is a membrane that is highly selective for the kinds of molecules or ions that is allows passing Membranes control the flow of information between cells and their surroundings, by specific receptors that are contain within the membranes. These receptors are compounds usually proteins that undergo specific reaction. For example, the response of a particular cell to insulin, in a chemical reaction with a specific receptor molecule in the membrane. Another chemical reaction can also occurs in membranes is photosynthesis.3. Structure of biological membranes: Phosphorus-containing lipids form membranes because they all possess an important common structural feature; A. A polar head and a non-polar tail: The non-polar hydrocarbon tail is called hydrophobic (water- repelling) part. The polar head (carboxylic end) is called hydrophilic (water- loving) part. When these lipids are placed in water, only a small fraction dissolves to form a true solution. The rest form micelles. These are aggregates of lipids in which the hydrocarbon tails gather together to avoid the aqueous solution. In this way, they form a hydrophobic region in the center of micelle. AMPHIPATHIC LIPID ” SO} Feo Fhane groupe polar or hycpneble gros Acco pace Aqueous phase ‘Aqueous phase ‘Aqueous phase tite bares wens Oo WATE UL ston ‘| renpster ee Pa ate MA i . a a coon me coh ae ate cote my cw RS ary ! z Formation of lipid membranes, micelles, emulsions, and liposomes from am- phipathic lipids, eq, phospholipids.B. Prot components: « Biological membranes also contain proteins that are located either completely or partially in the hydrophobic region of the bimolecular sheets. e These proteins carry out the various functions of membrane. ¢ [tis believed that each type of protein has a specific function e Some transport ions or molecules across the membrane. e Other act as receptor sites for specific molecules that carry messages to the cell. e It is known that proteins carry out the functions of the membranes, but scientist don't know in detail how they do it. 4. Transport across membranes: A. Passive transport — Movement of substances across a membrane, going down a gradient of concentration, pressure, or electrical charge. Does not require the cell to expend energy. 1. Simple diffusion _ Diffusion of water, dissolved gases, or lipid-soluble molecules through the phospholipid bilayer of a membrane 2. Facilitated diffusion Diffusion of (normally water-soluble) molecules through a channel or carrier protein. 3. Osmosis Diffusion of water across a differentially permeable membrane—that is, a membrane that is more permeable to water than to dissolved molecules. B. Energy-requiring — Movement of substances across a membrane, usually against a concentration transport gradient, using cellular energy. 1. Active transport Movement of individual small molecules or ions through membrane-spanning proteins, using cellular energy, normally ATP. 2. Endocytosis Movement of large particles, including large molecules or entire microorganisms, into a cell by engulfing extracellular material, as the plasma membrane forms membrane-bound sacs that enter the cytoplasm. 3. Bxogytosis Movement of materials out of a cell by enclosing the material in a membranous sac that moves to the cell surface, fuses with the plasma membrane, and opens to the ‘outside, allowing its contents to diffuse away.