Lipids - I - Chemical Structure and Function of Lipids PDF

CHEMICAL STRUCTURE AND FUNCTION OF LIPIDS Part - I Prof. Dr. Özlem Dalmızrak Near East University, Faculty Medicine, Department of Biochemistry, Lefkoşa, TRNC Prepared by Professor İzzet Hamdi ÖĞÜŞ  LIPIDS The lipid...

CHEMICAL STRUCTURE AND FUNCTION OF LIPIDS Part - I Prof. Dr. Özlem Dalmızrak Near East University, Faculty Medicine, Department of Biochemistry, Lefkoşa, TRNC Prepared by Professor İzzet Hamdi ÖĞÜŞ  LIPIDS The lipids are chemically diverse group of compounds, including fats, oils, steroids, waxes, and related compounds. They have the common property of being (1) relatively insoluble in water and (2) soluble in nonpolar solvents such as ether and chloroform.  LIPIDS BIOLOGICAL FUNCTIONS They are important dietary constituents because of their high energy value Fat-soluble vitamins and the essential fatty acids contained in the fat of natural foods have a vital importance. Fat is stored in adipose tissue, where it also serves as a thermal insulator in the subcutaneous tissues and around certain organs. Nonpolar lipids act as electrical insulators, allowing rapid propagation of depolarization waves along myelinated nerves. Combinations of lipid and protein (lipoproteins) are important cellular constituents, and serve as the means of transporting lipids in the blood. Fat is an efficient way to store excess energy Normal-weight, Obese, Type of Fuel 70 kg man 140 kg man Triacylglycerols (TG), kg (adipose tissue) 15 80 Proteins , kg (mainly muscle) 6 8 Glycogen , kg (muscle, liver) 0.25 0.25 Circulating fuels, kg (glucose, fatty acids, TG) 0.025 0.025 Estimated survival in case of starvation, 3 14 months FATTY ACIDS ARE HYDROCARBON DERIVATIVES Fatty acids are hydrocarbon chains of various lengths (C4 to C36) and degrees of unsaturation that terminate with carboxylic acid groups. The systematic name for a fatty acid is derived from the name of its parent hydrocarbon by the substitution of oic for the final. For example, the C18 saturated fatty acid called octadecanoic because the parent hydrocarbon is octadecane (Its common name is stearic acid). C16 fatty acid (Hexadecanoic acid, Palmitic acid) FATTY ACIDS ARE HYDROCARBON DERIVATIVES A C18 fatty acid; with one double bond is called octadecenoic acid; with two double bonds, octadecadienoic; and with three double bonds, octadecatrienoic acid. The notation 18:0 denotes a C18 fatty acid with no double bonds, whereas 18:2 signifies that there are two double bonds.  FATTY ACIDS ARE HYDROCARBON DERIVATIVES The most commonly occuring fatty acids have even numbers of carbon atoms in an unbranched chain of 12 to 24 carbons. There is also common pattern in the location of double bonds; in most monounsaturated fatty acids the double bond is between C-9 and C-10 (9), and the other double bonds of polyunsaturated fatty acids are generally 12 and 15. Thedouble bonds of polyunsaturated fatty acids are almost never conjugated (-CH=CH-CH=CH-), but are separated by a methylene group (-CH=CH-CH2-CH=CH-). NOMENCLATURE OF FATTY ACIDS Arachidonic acid all-cis 5,8,11,14 - eicosatetraenoic acid all-cis 6,9,12,15 - eicosatetraenoic acid SOME FATTY ACIDS OF PHYSIOLOGICAL IMPORTANCE COMMON NAME STRUCTURE Acetic acid 2:0 Propionic acid 3:0 Fatty acids Butyric acid 4:0 with chain Caproic acid 6:0 length of Caprylic acid 8:0 4- 10 carbons are found in Capric acid 10:0 signicant Lauric acid 12:0 quantities Myristic acid 14:0 in milk Palmitic acid 16:0 Palmitoleic acid 16:1 (9) Stearic acid 18:0 Oleic acid 18:1 (9) Essential Linoleic acid 18:2 (9,12) fatty acids -Linolenic acid 18:3 (9,12,15) Precursor of Arachidonic acid 20:4 (5,8,11,14) prostaglandins Lignoceric acid 24:0 Nervonic acid 24:1 (15)  Trans-unsaturated cis-Unsaturated Saturated fatty fatty fatty acids, acids, acids, have no theone have doublegeometric or isomers moreTheir bonds. double of bonds long naturally with cis- hydrophobic occurring chains cis-acids, configuration. are easily are not Because stacked of produced andbending bytheir they areinsolidmammalian (fat)chains, in room enzymes they but are usually temperature. are formed liquid by microorganisms (oil) at room temperature. in the gastrointestinal tract of ruminant mammals and chemically during commercial partial hydrogenation of fats and oils. Physical properties of fatty acids are dramatically changed by chain length and saturation level  CLASSIFICATION OF LIPIDS A. SIMPLE LIPIDS 1. Fatty acids 2. Waxes 3. Neutral lipids (Glycerides) - Storage lipids B. COMPLEX LIPIDS 1. Phospholipids a) Glycerophospholipids b) Plasmalogens c) Sphingophospholipids Membrane 2. Glycolipids lipids a) Sphingoglycolipids b) Galactolipids (sulfolipids) C. STEROIDS AND OTHER ISOPRENOID LIPIDS 1. Steroids (cholesterol, steroid hormones) 2. Terpenes 3. Carotenoid compounds (Vit A)  TRIACYLGLYCEROLS The simplest lipids constructed from fatty acids are the triacylglycerols (TAG), also referred to as triglycerides, fats, or neutral fats. Simple TAG - tripalmitin, tristearin, triolein Mixed TAG TAG’s are nonpolar, hydrophobic, essentially insoluble in water.  TRIACYLGLYCEROLS Triacylglycerols provide stored energy and insulation. Advantages of using TAG’s rather than polysaccharides? - Carbon atoms of fatty acids are more reduced than those of sugars. -The organism that carries fat as fuel does not have to carry the extra weight of water for hydration that is associated with the stored polysaccharides. Humans have fat tissue (composed primarily of adipocytes) under the skin, in the abdominal cavity and in the mammary glands. Insulation against low temperatures (seals, penguins, polar animals) Hibernating animals – Stored fats both have a function in providing energy and insulation. EVERY FAT SOURCE HAS A CHARACTERISTIC FATTY ACID COMPOSITION  Waxes Serve as Energy Stores and Water Repellents -COO- Free fatty -OOC-CH2-CH2-CH2-CH2-CH2-CH2-CH2-CH3 acid Wax -CO-O- A L C OH O L O ǁ CH3-(CH2)n-CH2-C-O-CH2-(CH2)x-CH3 Waxes are the esters of long-chain (C14 to C36) saturated and unsaturated fatty acids with long chain (C16 to C30) alcohols. CH2-O-CO-CH2-CH2-CH2-CH2-CH3 Triacylglycerol | (Triglycerides, CH-O-CO-CH2-CH2-CH2-CH2-CH2-CH2-CH3 | neutral lipids) CH2-O-CO-CH2-CH2-CH2-CH3 Triacylglycerols are fatty acid triesters of glycerol. They are nonpolar and water insoluble.  Waxes Serve as Energy Stores and Water Repellents Waxes also serve a diversity of other functions related to their water-repellent properties and their firm consistency. - Certain skin glands of vertebrates secrete waxes to protect hair and skin and keep it pliable, lubricated and waterproof. - Birds secrete waxes from their glands to keep their feathers water-repellent. - Many tropical plants are coated with a thick layer of waxes, which prevents excessive evaporation of water and protect against parasites.  CLASSIFICATION OF LIPIDS A. SIMPLE LIPIDS 1. Fatty acids 2. Waxes 3. Neutral lipids (Glycerides) - Storage lipids B. COMPLEX LIPIDS 1. Phospholipids a) Glycerophospholipids b) Plasmalogens c) Sphingophospholipids Membrane 2. Glycolipids lipids a) Sphingoglycolipids b) Galactolipids (sulfolipids) C. STEROIDS AND OTHER ISOPRENOID LIPIDS 1. Steroids (cholesterol, steroid hormones) 2. Terpenes 3. Carotenoid compounds (Vit A) GLYCEROPHOSPHOLIPIDS : Phosphatidic acid derivatives CH3-CH2-CH2-CH2-CH2-CH2-CH3-CO-O-CH2 | CH3-CH2-CH2-CH2-CH2-CH2-CH3-CO-O-CH | CH2-O-PO3H- Cell membrane P H Phosphatidic acid Glycerophospholipids (or phosphoglycerides) are the major lipid components of biological membranes. They consist of glycerol-3-phosphate esterified at its C1 and C2 positions to fatty acids and at its phosphoryl group to a group, X, to form the class of substances. The simplest glycerophospholipids, in which X=H, are phosphatidic acids; they are present only in small amounts in biological membranes. Glycerophospholipids are therefore amphipathic molecules with nonpolar aliphatic “tails” and polar phosphoryl-X “heads”. Hydrophobic tails of the molecule are embedded in biological membranes. GLYCEROPHOSPHOLIPIDS : Phosphatidic acid derivatives Glycerophospholipids are named according to the alcohols which is esterified to phosphoryl group. GLYCEROPHOSPHOLIPIDS : Phosphatidic acid derivatives Glycerophospholipids are named according to the alcohols which is esterified to phosphoryl group. P Ethanolamine Phosphatidyl- ethanolamine (Cephalin) Phosphatidyl- P Choline P Choline (Lecithin) Phosphatidyl- glycerol Phosphatidyl- P Serine serine P Cardiolipin P Phosphatidyl- P Ino inositol PHOSPHATIDYLINOSITOL   Second Messengers Cell membrane PI P Ino Kinases PIP2 P Ino P P Phospholipase C P Ino P P IP3 -OH DAG SOME GLYCEROPHOSPHOLIPIDS HAVE ETHER-LINKED FATTY ACIDS Plasmalogens Occur in Brain & Muscle These compounds constitute as much as 10% of the phos- pholipids of brain and muscle. Structurally, the plasmalogens resemble phosphatidylethanol- amine but possess an ether link on the sn-1 carbon (vinyl ether) 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. SOME GLYCEROPHOSPHOLIPIDS HAVE ETHER-LINKED FATTY ACIDS Platelet-activating factor is released from leukocytes called basophils and stimulate platelet aggregation and release of serotonin (a vasoconstrictor) from platelets. It also exerts a variety of effects on liver, smooth muscle, heart, uterine and lung tissues and plays an important role in inflammation and allergic response.  CHLOROPLASTS CONTAIN GALACTOLIPIDS AND SULFOLIPIDS Galactolipids predominate in plants cells. One or two galactose residues are connected to C3 of 1,2-diacylglycerol by a glycosidic linkage They are localized in the thylakoid membranes of chloroplast in plants. They are probably the most abundant membrane lipid on the biosphere. Sulfolipids are the sulfonated form of glycolipids (DGDG).  SPHINGOPHOSPHOLIPIDS HO-CH-CH=CH-(CH2)12-CH3 Sphingosine | CH-NH2 H2N- | -OH HO-CH2 HO-CH-CH=CH-(CH2)12-CH3 Ceramide | -NH- CH-NH-CO-CH2-CH2-CH2-CH2-CH3 -OH | HO-CH2 Fatty acid A fatty acid is linked to sphingosine backbone with an amide bond. Sphingomyelin -NH- P Choline Primary hydroxyl group of sphingosine is esterified to a phosphocholine. The membranous myelin sheath that surrounds and electrically insulates many nerve cell axons is particularly rich in sphingomyelin.  SPHINGOGLYCOLIPIDS Cerebrosides -NH- -NH- -OHGlc -OHGal Galactosylceramide (GalCer) Glucosylceramide (GlcCer) Galactosylceramide (GalCer) is a major Glucosylceramide (GlcCer) is the major lipid of myelin. glycolipid of extraneural tissues and a precursor of more complex sphingo- glycolipids. -NH- Gal -NH- Sulfatide O-SO3H- Glc Gal Lactosylceramide Gangliosides Gal + Nac-Gal -NH- Glc Gal -NH- Glc Gal Gal NANA; N-acetylneura- minic acid (sialic acid) NANA Globoside BLOOD GROUP ANTIGENS ARE SPHINGOGLYCOLIPID SPHINGOGLYCOLIPIDS Phospholipids and sphingolipids are degraded in lysosome. Gangliosides are degraded by a set of lysosomal enzymes that catalyze the stepwise removal of sugar units, finally yielding ceramide. A genetic defect in any of these hydrolytic enzymes leads to the accumulation of gangliosides in the cell, with severe medical consequences.  STEROLS Sterols are structural lipids present in the membranes of most eukaryotic cells. Cholesterol is the major sterol in animal tissues, is amphipathic, with a polar head group and non-polar hydrocarbon body. Stigmasterol - in plants Ergosterol – in fungi Sterols also serve as precursors for variety of products with specific biological activities. Steroid hormones Bile acids