Lipids 2024 PDF

Lipids  Introduction  Lipids are a heterogeneous group of organic compounds defined by their solubility in nonpolar solvents such as chloroform, ether, and benzene and by their poor solubility in water. Unlike the polysaccharides ,proteins and nucleic acids, lipids are not polymers. Furth...

Lipids  Introduction  Lipids are a heterogeneous group of organic compounds defined by their solubility in nonpolar solvents such as chloroform, ether, and benzene and by their poor solubility in water. Unlike the polysaccharides ,proteins and nucleic acids, lipids are not polymers. Further, lipids are mostly small molecules.  Lipids may be polar or nonpolar (amphipathic).  Major polar lipids include fatty acids, cholesterol, glycerophosphatides, and glycosphingolipids.  Very short chain fatty acids and ketone bodies are readily soluble in water. Occurrence  Lipids present in humans, animals, plants and micro-organisms to some extent.  Animal fat, egg yolk, butter and cheese are lipids of animal origin.  vegetable or cooking oils are lipids are plant origin. Functions of lipids 1. Under skin it serve as thermal insulator against cold. 2. Fat around kidney serve as padding against injury. 3. Serve as a source of energy for cell like carbohydrates. 4. It is an ideal form of storing energy in the human body compared to carbohydrates and proteins because: (a) Energy content of fat is higher. , 5. Lipids are structural components of cell membrane and nervous tissue. 6. Some lipids serve as precursors for the synthesis of complex molecules. For example, acetyl-CoA is used for the synthesis of cholesterol. 7. Lipoproteins, which are complexes of lipids and proteins are involved in the transport of lipids in the blood and components of cell membrane. 8. Some lipids serve as hormones and fat soluble vitamins are lipids. 9. Fats are essential for the absorption of fat soluble vitamins.  , 11. Eicosanoids which have profound biological actions are derived from the essential fatty acids. 12. Lipids present in myelinated nerves act as insulators for propagation of depolarization wave. 13. Some saturated fatty acids are anti-microbial and anti-fungal agents. 14.Lipids are an important group of antigens of parasites that cause filariasis, cysticercosis, leishmaniasis and schistosomiasis in third world countries.  Anti-lipid antibodies are found in the blood of individuals affected with these diseases. 15. Saturated free fatty acids (SFFAs) are pheromones of animals like tiger etc... Classification of Lipids  Lipids Complex/ Compound Simple Derived Gl Fatt yc Pho Sul Lip y Fat Caro Fat or oli sph foli opr Sol oil Waxes olip pid ote Acid Vita tenoi pi ids s ins s/Ste ds ds mins roids  Classification of Lipids Lipids are broadly classified into simple, complex, derived and miscellaneous lipids, which are further subdivided into different groups. 1. Simple lipids:- esters of fatty acids with different alcohols. a. Fats and oils ( TAGs) :- These are esters of fatty acids with glycerol.  The difference between fat and oil is only physical. Thus, oil is a liquid while fat is a solid at room temperature.  2. Complex (Compound) lipids These are esters of fatty acids with alcohols containing additional groups such as phosphate, nitrogenous base, carbohydrate, protein …etc. A. Phospholipids:- Esters of the above type containing phosphoric acid and frequently a nitrogenous base. i) Glycerophospholipids  These phospholipids contain glycerol as the alcohol E.g. lecithin, cephalin. ii) Sphingophospholipids  The alcohol is sphingosine. B. Glycolipids These lipids contain a fatty acid, carbohydrate and nitrogenous base.  The alcohol is sphingosine, hence they are also called as glycosphingolipids.  Glycerol and phosphate are absent. E.g. Cerebrosides, gangliosides. C. Lipoproteins:  Macromolecular complexes of lipids with proteins. D. Other complex lipids:  Sulfolipids, amino lipids and lipopolysaccharides are among the other complex lipids.  3. Derived lipids These are the derivatives obtained on the hydrolysis of simple and complex lipids which possess the characteristics of lipids.  These include fatty acids, mono- and diacylglycerols, lipid(fat) soluble vitamins, steroid hormones, cholesterol and ketone bodies. 4. Miscellaneous lipids: These include a large number of compounds possessing the characteristics of lipids. E.g., carotenoids, squalene,hydrocarbons such as pentacosane(in bees wax), terpenes etc. Neutral Lipids:  Fatty acids  Are carboxylic acids with hydrocarbon side chain.  They are the simplest form of lipids.  The anionic group has an affinity for water, giving the fatty acid its amphipathic nature (having both a hydrophilic and a hydrophobic region).  …cont’d  Fatty acids with less than 12 and more than 24 carbon atoms are uncommon in biological systems. Palmitic acid (l6C) and stearic acid(18) are the most common. Most of the fatty acids have even number of carbon atoms. This is due to biosynthesis of fatty acids mainly occurs with the sequential addition of 2 carbon units.  ,, Long-chain fatty acids (LCFAs), the hydrophobic portion is predominant. highly water-insoluble, and must be transported in the circulation in association with protein. More than 90% of the fatty acids found in plasma are in the form of fatty acid esters (primarily triacylglycerol, cholesteryl esters, and phospholipids) contained in circulating lipoprotein particles..  Unesterified (free) fatty acids are transported in the circulation in association  Based on the nature of …cont’d hydrocarbon side chain, they are divided into: A. Saturated fatty acids:  contain no double bonds—that is, be saturated  they can not undergo further hydrogenation. Fig. A saturated (A) and an unsaturated (B) fatty acid. B. Unsaturated fatty NB: Cis double bonds cause a fatty acids: acid to “kink.”  contain one or more. A. Saturated fatty acids  All C bonded to H No double bonds long, straight chain most animal fats solid at room temp.  contributes to cardiovascular disease (atherosclerosis) = plaque deposits  B. Unsaturated fatty acids Have a double bonds in the fatty acids plant & fish fats vegetable oils liquid at room temperature the kinks made by double bonded C prevent the molecules from packing tightly together In which hydrocarbon side chain is , unsaturated (one or more double bonds are present). All the naturally occurring unsaturated fatty acids are cis-isomers. Cis and trans isomers are not interchangeable in cells. Only cis isomers can fit into cell membrane because of bend at double bond.  Trans Fats – The Double Whammy  Trans fats come from adding hydrogen to vegetable oil (unsaturated fats) through a process called hydrogenation.  “Partially hydrogenated” oils may contain higher levels of trans fats.  Trans fats are more solid than oils.  Trans fats increase the shelf life 20 of foods. Fatty Acid Structure Why would the type of fatty acid determine its state at room temperature? Double bonds create the kinks in the structure can’t be packed as closely together  less Van der waals forces intraction. This makes them more fluid at room temperature  lower melting temperature The peanut butter puzzle… Fats are usually found in animals Oils are usually found in plants So why is peanut butter solid? hydrogenation Saturated vs. unsaturated saturated unsaturated   Nomenclature of fatty acids The naming of a fatty acid (systematic name) is based on the hydrocarbon from which it is derived. The saturated fatty acids end with a suffix -anoic (e.g. octadecanoic acid) while the unsaturated fatty acids end with a suffix –enoic (e.g. octadecenoic acid). In addition to systematic names/ fatty acids have common names which are more widely used.  Numbering of carbon atoms It starts from the carboxyl carbon which is taken as number 1. The carbons adjacent to this (carboxyl C) are 2, 3, 4 and so on or alternately α , β, γ and so on. The terminal carbon containing methyl group is known omega (ω) carbon.  Starting from the methyl end, the carbon atoms in a fatty acid are numbered as omega 1, 2, 3 etc.  Shorthand representation of fatty acids The total number of carbon atoms are written first, followed by the number of double bonds and finally the (first carbon) position of double bonds, starting from the carboxyl end. Thus, saturated fatty acid, palmitic acid is written as l6:0 oleicacid as 18:1;9, Arachidonic acid as 20 : 4; 5, 8, 11, 14. Δ9 indicates that the double bond is between 9 and 10 of the fatty acid.  Essential fatty acids They are not synthesized in the body. Two fatty acids are dietary essentials in humans :  linoleic acid- which is the precursor of arachidonic acid, the substrate for prostaglandin synthesis.  α-linolenic acid- important for growth and development.  Arachidonic acid becomes essential if linoleic acid is deficient in the diet.  Essential fatty acid deficiency can result in a  Alpha-linolenic acid – omega-3 fatty acid Linoleic acid - omega-6 fatty acid Table. Common names and structures of some fatty acids of physiologic importance. 28  Shorthand representation of fatty acids Linoleic acid CH3(CH2)4CH=CHCH2CH=CH(CH2)7COOH 18:2 n-6 Alpha-linolenic acid CH3CH2CH=CHCH2CH=CHCH2CH=CH(CH2)7COOH 18:3 n-3 Eicosapentaenoic acid(EPA, fish oil) CH3CH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CHCH2CH=CH(CH2)3COOH 20:5 n-3  NB: Humans have carbon 9, 6, 5 and 4 , desaturases, but lack the enzymes to insert double bonds at carbon atoms beyond C-9 in the fatty acid chain. This is the basis for the nutritional essentiality of the polyunsaturated linoleic (cis double bonds) ,and α-linolenic acids(has all cis double bonds). Essential fatty acids are required for: membrane structure and function, transport of cholesterol, formation of lipoproteins, prevention of fatty liver etc. Good sources of ‘omega-3 fatty acids’ Oily fish (salmon, mackerel, sardines, tuna) Pumpkin seeds, sesame seeds soybean oil  Good sources of ‘omega-6 fatty acids’ Most vegetable oil, Sunflower oil, Corn oil, Soybean oil Cotton seeds oil Pumpkin seeds Nuts and cereals Poultry, eggs Avocado 1. Storage lipids  The fats and oils used almost universally as stored forms of energy in living organisms are derivatives of fatty acids.  Two types of fatty acid–containing compounds,  triacylglycerols and  waxes.  They are esters of fatty acids with alcohols.  An Formation of an ester: ester is formed when acid reacts with alcohol. O O R'OH + HO-C-R" R'-O-C-R'' + H2O Eg. Fats and waxes Fats ,  Esters of fatty acids with glycerol.  Also called as triglycerides or triacylglycerols. because all the three hydroxyl groups of glycerol are esterified. Fats are also called as neutral fats. , Triacylglycerol Formation of an ester: O O R'OH + HO-C-R" R'-O-C-R'' + H2O  Structure of Triacylglycerol/ fats  3 fatty acids linked to glycerol.  i.e. three molecules of fatty acids esterified with one molecule of glycerol.  All the three fatty acids can be same or different. Functions of Triglycerides 1.They function as storage lipids in animals and in plants. 2. In man adipose tissue or fat tissue found under the skin, in the abdominal cavity and in the mammary gland contain triacylglycerols.. …Cont’d 3. In other animals and plant cells also triacylglycerols are found as tiny droplets in cytosol. 4. The fat stored under the skin serve as energy store and as insulator against cold. 5. Women have more fat than men. 6. In obese (fat) people, many kilograms of triacylglycerol is stored under the skin. 7. The antarctic and arctic animals like seals Physical Properties of TAGs 1. Pure fats have no colour, taste and odour. 2. At room temperature,  fat of plant origin remains oil because it contains more unsaturated fatty acids where as animal fat remain as solid, because it contains mostly saturated fatty acids. 3. Triglycerides containing asymmetric carbon atom are optically active.  Steroids  Steroids are complex molecules containing four fused rings. The four fused rings makeup ‘cyclopentanoperhydrophenanthrene’(CPPP) or ‘sterane’ ring. Sterane ring is also called as steroid nucleus. The most abundant steroids are sterols which are steroid alcohols. Fig. structure of steroid Cholesterol.  COMPOUND LIPIDS When a lipid contains an element or moiety in addition to fatty acids and alcohol present in simple fats, it is known as a compound or conjugated lipid.  Saturated C16 or C18 FA Phosphodiest Unsaturated C16 – C20 FA er linkage Derived from polar alcohol  smallest = H (from H-OH)  least common in membranes  phosphatidic acid  Cardiolipin Cardiolipin isan important component of the inner mitochondrial membrane  This the only human glycerophospholipid that is antigenic.  For example,cardiolipin is recognized by antibodies raised against Treponema pallidum, the bacterium that causes syphylis.  Cardiolipins are used in serological diagnosis of syphilis and autoimmune diseases. Plasmalogens Platelet-activating factor (PAF)  PAF is synthesized /released by a variety of cell types. binds to surface receptors, triggering potent thrombotic and acute inflammatory events. PAF activates inflammatory cells and mediates hyper­- sensitivity, acute inflammatory, and anaphylactic reactions.  neutrophils causes platelets to aggregate and  Sphingophospholipids S Sphingomyelin is an important constituent of the myelin of nerve fibers. T T The myelin sheath is a layered, membranous structure that insulates and protects neuronal fibers of the central nervous system. Sphingophospholipids  Ceramide OH O CH3 (H2C)12 CH CH CH CH NH C R1 Sphingosine Fatty acid CH2 O CH3 Phosphate O P O CH2 CH2 N+ CH3 Choline OH CH3 Sphingomyelin Sphingomyelins are found in large amounts in brain and nerves and in smaller amounts in lung, spleen, kidney, liver and blood. Sphingomyelins differ from lecithins and cephalins in that they contain sphingosine as the alcohol instead of glycerol, they contain two nitrogenous bases: sphingosine itself and choline.  Glycolipids  Glycolipids are lipids that contain carbohydrate residues in addition to the alcohol (sphingosine) and a very long-chain fatty acid (24-carbon series).  They are present in cerebral tissues and, therefore, are called cerebrosides.  They are also referred to as sphingogalactolipids or galactosides as galactose is an important constituent of their structure.  Classification of glycolipids: According to the number and nature of the carbohydrate residue(s) present in the glycolipids the following types exist:  Cerebrosides: They have one galactose molecule (galactosides).  Sulfatides: They are cerebrosides with sulfate substitution on the sugar (sulfated cerebrosides). Glycolipids help form insulation for nervous system electrical activity  Negatively charged gangliosides in glia membrane  Repel negative ions & attract positive ions  Myelin insulation greatly increases the speed of action potentials  Glycolipids  Pattern of sugar residues is variable  Always in outer leaflet of cell membrane, & inner leaflet of organelles Hydrophilic (soluble) Hydrophobic (not soluble = lipophilic)  Cerebrosides  The cerebrosides, as the name suggest (cerebral = related to brain), occur in myelin sheath of nerves and white matter of the brain tissues and cellular membranes.  They are important for nerve conductance. They contain sugar, usually -galactose (sometimes glucose or lactose), Ceramide sphingosine and Cerebron fatty acid, (Phrenosin) but contains cerebronic acid (2- no phosphoric acid. hydroxylignoceric acid) and OH O galactose. CH3 (H2C)12 CH CH CH CH NH C R1 Nervon contains nervonic acid Sphingosine Fatty acid (lignoceric acid unsaturated at CH2 C15) and galactose. CH2OH Oxynervon contains oxynervonic O OH H O acid (2-hydroxynervonic acid) and Galactose galactose. OH H H H Other Cerebrosides: Some H OH cerebrosides contain carbohydrates other than Psychosin galactose Cerebroside  Gangliosides  They are compound lipids present in gray matter of the brain, ganglionic cells, and RBCs.  They are composed of a glycosphingolipid (ceramide and oligosaccharide) with one or more sialic acids (i.e., N-acetylneuraminic acid; NANA) linked as a branch to the sugar chain.  Gangliosides are classified according to the oligosaccharide attached to ceramide.  The basic oligosaccharide unit attached to ganglioside GM1 consists of five monosaccharides, i.e., Ceramide-Glucose  Galactose (NANA)  N- Acetylgalactosamine  Galactose (with NANA attached to the first galactose).  GM1ganglioside is the site of attachment of the Vibrio cholerae exotoxin that causes the acute diarrhea of  Although a minor membrane component (~2%), glycolipids have some special functions  Gangliosides in neurons  Oligosaccharides with negatively charged sialic acid residues  Attract positive ions, e.g. Ca++  Affects electrical properties & signaling  Gangliosides act as Receptors Gangliosidoses As components of the cell plasma membrane, gangliosides modulate cell signal transduction events. They have recently been found to be highly important in immunology. They transfer biogenic amines across the cell membrane and act as cell membrane receptors. They work as the receptors for cholera toxin on the human intestine mucosal cells and as receptors for certain viruses. Natural and semi-synthetic gangliosides are considered the potential therapeutic agents for neurodegenerative disorders.  Sphingolipids at Cell Surfaces are Sites of Biological Recognition  In humans, at least 60 different sphingolipids have been identified in cellular membranes  Many of these are prominent in the plasma membranes of neurons Glycosphingolipids as  determinants of blood groups:  The carbohydrate moieties of certain sphingolipids;  define the human blood groups  therefore determine the type of blood Fuc sugar  5 Lipid rafts have higher concentrations of -  Sphingolipid  Cholesterol  Glycolipids Lipoproteins  Lipoproteins are lipids combined with proteins in the tissues. The lipid component could be a phospholipids, cholesterol or triglycerides. The lipoproteins could be described as of two types.  Structural lipoproteins: These are widely distributed in tissues, being present in cellular and subcellular membranes. In lung tissues, they act as surfactants in a complex of a protein and lecithin. In the eye, rhodopsin of rods is a lipoprotein complex.  Transport lipoproteins: These are the forms present in blood plasma. They are composed of a protein called apolipoprotein and different types of lipids. (Cholesterol, cholesterol esters, phospholipids and triglycerides). As the lipid content increases, the density of plasma lipoproteins decreases and the diameter increases and vice versa.  Classification of Lipoproteins  Lipoproteins are classified by their density which, in turn, reflects size. The greater the lipid/protein ratio in the complex, the larger it is and the lower its density.  There are five main classes of lipoproteins. Triglyceride-rich particles include :  Chylomicrons, which transport exogenous lipid from the intestine to all the cells.  VLDL (very low density lipoproteins), which transport endogenous lipid from the liver to cells;.  IDL (intermediate density lipoproteins), which are usually undetectable in normal plasma. It is normally a transient intermediate lipoprotein formed during the conversion of VLDL to LDL.  It contains both cholesterol and endogenous triglycerides. Classification of Lipoproteins LDL (low density lipoproteins): formed from VLDL, transport cholesterol to cells.  HDL (high density lipoproteins): These are involved in the transport of cholesterol from the cells to the liver. LDL and HDL are two smaller lipoproteins contain mostly cholesterol. The classes of lipoproteins are chylomicrons, VLDLs, IDLs, LDLs, and HDLs. Classification of Lipoproteins Chylomicrons: synthesized in small intestine and secreted into the lymph. Apolipoprotein present:- Apo-B, Apo AI, ApoAII, ApoAIV, ApoCII, ApoCIII, ApoE. composition:  1 % protein.  87 % triglyceride.  8 % phospholipid.  3 % cholesteryl ester.  1 % free cholesterol.  Lipoprotein Classification Very low density lipoproteins (VLDL) synthesized in the liver, rich in triglyceride apo-lipoproteins:  Apo-B100, ApoC-III, Apo-E, ApoA-I, ApoA-II composition:  7 - 10 % protein.  50 - 55 % triglyceride.  18 - 20 % phospholipid.  12 - 15 % cholesteryl ester.  8 - 10 % free cholesterol.  Low density lipoproteins (LDL) LDL and IDL, are the catabolic products of VLDL apo-lipoproteins present: Apo-B Composition:  20 - 22 % protein  12 - 15 % triglyceride  20 - 28 % phospholipid  37 - 48 % cholesteryl ester  8 - 10 % free cholesterol  High density lipoproteins (HDL) formed around ApoAI secreted from liver and intestine. apo –lipoproteins present: Apo A-I, Apo A-II, ApoAIV, ApoCIII, ApoE Composition:  33 - 57 % protein  3 - 15 % triglyceride  26 - 43 % phospholipid  15 - 30 % cholesteryl ester  2 - 10 % free cholesterol HDLs are used for the transport of lipid through the circulatory system to the liver, and high levels of HDLs forecast a low risk of heart attack. In contrast, high levels of LDLs (which transport cholesterol to the non- hepatic tissues) are considered cautionary. D stands for “density” in these acronyms because fat has a density of about 0.88 g/ml, whereas protein has a density of about 1.0 g/ml. In consequence, the higher the fat content, the lower the density of the particle.   Since cholesterol is hydrophobic (water fearing) and blood is hydrophilic (water loving), the two do not mix.  Cholesterol is carried through the bloodstream in protein packages called lipoproteins, made up of lipid on the inside and protein on the outside.  Two kinds of lipoproteins carry cholesterol throughout your body. - High density lipoproteins (HDL) - Low density lipoproteins (LDL) 70  LDL and HDL …cont’d LDL cholesterol is sometimes called bad cholesterol. High LDL cholesterol leads to a buildup of cholesterol in arteries. The higher the LDL level in your blood, the greater chance you have of getting heart disease. HDL cholesterol is sometimes called good cholesterol. HDL carries cholesterol from other parts of your body back to your liver. The liver 71 removes the cholesterol from your body.