Biochemistry - 03 Lipids

BIOCHEMISTRY acquiring a characteristic disagreeable odor. One cause of the odor is the release of volatile fatty acids by hydrolysis of the ester bonds. Butter, for example, releases foul-smelling butyric, caprylic, and capric acids. Microorganisms present in the air furnish lipases that catalyze this process. Hydrolytic rancidity can easily be prevented by covering the fat or oil and keeping it in a refrigerator. MODULE 3 - LIPIDS LESSON 1 - INTRODUCTION TO LIPIDS: PROPERTIES, FUNCTIONS AND REACTIONS PROPERTIES OF LIPIDS • • Lipids o Heterogeneous group of compounds that are related more by physical than by their chemical properties. o Relatively insoluble in water and soluble in a nonpolar solvent. o Greasy to touch; leaves permanent oily stain on paper. o Lighter than water. o Poor conductors of heat and electricity and therefore serve as excellent insulators for the body, slowing the loss of heat through the skin. Pure lipids o Colorless with bland odor and taste. o When heated strongly, undergoes decomposition forming acrid flammable vapors and when ignited, they burn with a sooty flame. LESSON 2 - CLASSIFICATION OF LIPIDS BASED ON THEIR REACTION WITH WATER • • FUNCTIONS OF LIPIDS • • • • Lipids are a major source of energy for the body, and they also provide the hydrophobic barrier that permits partitioning of the aqueous contents of cells and subcellular structures. They serve additional functions in the body, for example, some fat-soluble vitamins have regulatory or coenzyme functions, and the prostaglandins and steroid hormones play major roles in the control of the body’s homeostasis. Lipids also act as precursors for other lipids and play a role in the transport of other lipids in the body. They also function as emulsifying agents in the gastrointestinal tract. Deficiencies or imbalances of lipid metabolism can lead to some of the major clinical problems encountered by physicians, such as atherosclerosis and obesity. BASED ON THEIR STRUCTURE • • • REACTIONS OF LIPIDS • • • Hydrolysis o Fats and oils can be hydrolyzed in the presence of an acid, a base, or specific enzymes known as lipases. The hydrolysis of fats and oils in the presence of a base is used to make soap and is called saponification. Hydrogenation o The double bonds in fats and oils can undergo hydrogenation. The hydrogenation of vegetable oils to produce semisolid fats is an important process in the food industry. Chemically, it is essentially identical to catalytic hydrogenation rxn described for alkenes. o In commercial processes, the number of double bonds that are hydrogenated is carefully controlled to produce fats with the desired consistency (soft and pliable). In preparation of margarine, for example, partially hydrogenated oils are mixed with water, salt, and nonfat dry milk, along with flavoring agents, coloring agents, and vitamins A and D, which are added to approximate the look, taste, nutrition of butter. Oxidation o Fats and oils that are in contact with moist air at room temperature eventually undergo oxidation and hydrolysis reactions that cause them to turn rancid, Hydrolyzable lipids o These are compounds that can be converted into smaller molecules by hydrolysis. o These are compounds that are derived from fatty acids. o E.g.: Fats, oils, waxes, phospholipids, lipoproteins Non-hydrolyzable lipids o These are compounds that cannot be cleaved into smaller molecules by hydrolysis. o E.g.: steroids, prostaglandins, vitamins, hormones Simple lipids o Esters of fatty acids with various alcohols. o Examples: triglycerides and waxes Complex lipids o Lipids containing parts other than fatty acids and alcohol. o Found in cell membranes, brain, nervous tissues, myelin sheaths of nerves, and blood platelets o E.g: phospholipids, sphingolipids, glycolipids, and lipoproteins Derived lipids o These compounds are products of hydrolysis of simple and complex lipids o E.g.: steroids, prostaglandins, vitamins, hormones LESSON 3 - FATTY ACIDS INTRODUCTION • • • • Fatty acids are carboxylic acids with long, unbranched carbon chains. Naturally occurring fatty acids have an even number of carbon atoms. They contain a polar end and a non-polar end. Apart from the carboxylic acid (COOH) group, fatty acids have no functional groups, except that some do have double bonds. Fatty acids can be classified as saturated or unsaturated. Saturated fatty acids - only contain single bonds while Unsaturated fatty acids o Contain at least one double bond. o Unsaturated fatty acids with one double bond are called monounsaturated fatty acids while those with two or more double bonds are called polyunsaturated fatty acids. o Unsaturated fatty acids can be classified as cis fatty acids or trans-fatty acid. cis Fatty acids have two hydrogen atoms on the same side of the double bond, which creates a kink in the structure. trans Fatty acids have two hydrogen atoms on the opposite side of the double bond, which results in a similar structure to that of saturated fatty acid. • NAMING FATTY ACIDS • • Fatty acids can be named using a shorthand nomenclature. First, count the number of carbons. Next, count the number of double bonds and note their position: Delta – starting from the carboxylic end, and omega – starting from the methyl end. Geometric isomerism in unsaturated fatty acid o cis ▪ The acyl chain are on the same side of the bond ▪ Oleic acid o trans ▪ The acyl chain is on the opposite side ▪ Elaidic acid NOMENCLATURE Write the number of carbons followed by a colon and the number of double bonds present, if any. For unsaturated fatty acids, indicate if you started counting from the delta or omega end. For example: • • • Δ7 • 10:1 Essential fatty acids - fatty acids that cannot be produced by the body. It includes alpha-linolenic acid (ALA) and linoleic acid (LA). o α-linolenic acid is the parent fatty acid of the omega-3 family o Linoleic acid is the parent fatty acid of the omega-6 family FATTY ACIDS • • • Are aliphatic carboxylic acids Occur mainly as esters of natural fats and oils but do occur in the unesterified form as free fatty acids ( transport form found in the plasma) In natural fats, they are usually straight-chain derivatives containing an even number of carbon atoms. o Saturated – no double bonds o Unsaturated – containing one or more double bonds STRUCTURE OF FATTY ACIDS • The terms saturated, mono-unsaturated, and polyunsaturated refer to the number of hydrogens attached to the hydrocarbon tails of the fatty acids as compared to the number of double bonds between carbon atoms in the tail. • • • • Named after the corresponding hydrocarbons with the same number and arrangement of carbon atoms, with-oic being substituted for the final –e –anoic – saturated acid ends (e.g.,octanoic acid) –enoic – unsaturated acids with double bonds (e.g., octadecenoic acid) C atoms are numbered from the carboxyl C as C-1 Adjacent to carboxyl C as 2,3 and 4 are also known as , , and  carbons, respectively Terminal methyl C is known as  or n-carbon  is used conventionally to indicate the number and position of the double bond, eg., 9 , double bond between C-9 and C-10 SATURATED FATTY ACIDS COMMON NAME # OF C ATOMS Acetic 2 Butyric Valeric 4 5 Caproic 6 Lauric 12 Myristic 14 Palmitic Stearic 16 18 ` Major end product of carbohydrate fermentation by rumen organism • In certain fats in small amounts (butter) • End product of carbohydrate fermentation by rumen organisms Spermaceti, cinnamon, palm kernel, coconut oils, laurels, butter Nutmeg, palm kernel, coconut oils, myrtles, butter Common in all animal and plant UNSATURATED FATTY ACIDS • • • • Monounsaturated o Monoethenoid, monoenoic o Acids containing double bond Polyunsaturated o Polyethenoid, polyenoic o Acids containing two or more double bonds Eicosanoids o Derived from eicosa (20 carbon) polyenoic fatty acids o Arachidonic acid is the major precursors ▪ Prostanoids ▪ Leukotrienes (LTs ) ▪ Lipoxins (LXs) LESSON 4 - SIMPLE AND COMPLEX LIPIDS SIMPLE LIPIDS • • • • Triglycerides o Also known as triacylglycerols o Humans store energy as triglycerides in adipose cells below the surface of the skin, in the breast area, and surrounding internal organs. o Hydrolyzed by enzymes (lipases) to produce energy. o Complete metabolism of a triglycerides yields: CO2, H2O, and energy. Fats o A mixture of triglycerides containing a high proportion of long-chain, saturated fatty acids o Mostly obtained from animals o Fats have higher melting points o Solids at room temperature. Oils o A mixture of triglycerides containing a high proportion of long-chain, unsaturated fatty acids, or short-chain, saturated fatty acids o Oils are fats in the liquid state o Oils have lower melting points o Liquids at room temperature. o Mostly obtained from plants and fish Waxes o They are esters of fatty acids with high molecular weight alcohols. o Because of their long nonpolar C chains, waxes are very hydrophobic. o Form protective coating on plants and fruits, and in animal COMPLEX LIPIDS • • • Phospholipids o Also called phosphoglycerides/glycerophospholipids o Long-chain fatty acids on a glycerol backbone attached to a phosphoric acid molecule containing an alcohol substituent. (usually amino alcohol) o The essential components of cell membranes and are found in small concentrations in other parts of the cell. Sphingolipids o Class of lipids built from long-chained fatty acids attached to sphingosine backbone rather than glycerol. o Sphingomyelin - Found in the myelin sheath surrounding nerve cells Glycolipids - Often called cerebrosides because of their abundance in brain tissue • Lipoproteins o Lipoproteins are the primary means of transport of cholesterol among tissues o Secreted by the small intestine and liver into the circulating blood o Composed of lipids & special proteins (apolipoproteins) o Chylomicron - formed in the mucosal cell of the intestine. They deliver triglycerides to the adipose tissue and muscle. They also deliver dietary cholesterol to the liver o Very Low-Density Lipoproteins - formed in the liver for the export of triglycerides. They transport triglycerides from the liver to the muscle and adipose tissue for storage or energy. o Low-Density Lipoproteins - primary carriers of cholesterol in the blood for delivery to the tissues. o High-Density Lipoproteins - scavengers for cholesterol from peripheral tissues. They also return cholesterol to the liver for metabolism. COMPLEX LIPIDS (PPT) Phospholipids o Main lipid constituents of membrane o Derivatives of phosphatidic acid o Phosphate - esterified with the – OH of a suitable alcohol o Phosphatidic acid – intermediate in the synthesis of triacylglycerols o Phospholipid biosynthetic pathway • • • • • Phosphatidylcholine o Phosphoacylglycerol containing choline o Most abundant phospholipids of the cell membrane and represent a large proportion of the body’s store of choline o Choline – important in nervous transmission, as acetylcholine, and as a store of labile methyl group Dipalmitoyl Lecithin o Major constituent of the surfactant preventing adherence, due to surface tension, of the inner surfaces of the lungs. o Absence from the lungs of premature infants causes respiratory distress syndrome Phosphatidylethanolamine (Cephalin) o Ethanolamine replaces choline o Lipid found in biological membranes o Cephalin is found particularly in nervous tissue such as the white matter of brain, nerves, neural tissue, and in spinal cord o Cephalin is the principal phospholipid in bacteria. Phosphatidylserine o Serine replaces choline o Found in most tissues o US-FDA “qualified claim” states that ▪ "Consumption of phosphatidylserine may reduce risk of dementia in elderly" and; ▪ "Consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly". Phosphatidylinositol o Precursor of second messenger o Inositol is present as stereoisomer, myoinositol o Phosphatidylinositol 4,5-biphosphate important constituent of the cell membrane phospholipids and cleaved into diacylglycerol and inositol triphosphate (internal signals or second messenger) • Cardiolipin o bisphosphatidyl glycerol o Important component of the inner mitochondrial membrane, where it constitutes about 20% of total lipid o Serves as insulator and stabilizes the activity of protein complexes important to the electron transport chain • Lysophospholipids o Intermediates in the metabolism of phosphoglycerols o Important in the metabolism and interconversions of phospholipids (lysophosphatidylcholine) o Found in oxidized lipoproteins and can promote atheroschlerosis Plasmalogens o 10% of the phospholipids of the brain and muscle o Resemble phosphatidylethanolamine (ether linked) o Alkyl radical is unsaturated alcohol o Choline, serine or inositol -may be substituted for ethanolamine Sphingomyelins o Found in large quantities in brain and nerve tissues o Yields fatty acid, phosphoric acid, choline, and a complex amino alcohol, sphingosine • • • • • Ceramide o Sphingosine plus amino acid o Structure found in glycosphingolipids • • Glycolipids (Glycosphingolipids) o Distributed in every tissue of the body ▪ Nervous tissues (brain) ▪ Plasma membrane – cell surface carbohydrates o Glycosphingolipids ▪ Major glycolipids in animal tissues ▪ Ceramide + sugar o Galactosylceramide - major sphingolipid of brain & other nervous tissue, C24 fatty acids o Gangliosides ▪ Are complex glycosphingolipids derived from glucosylceramide that contain in addition one or more molecules of a sialic acid ▪ Neuraminic Acid – principal sialic acid found in human tissues. ▪ GM3 – contains ceramide, one molecule of glucose, one molecule of galactose and one molecule of NeuAc • The simplest gangliosides in tissues • Fat-Soluble Vitamins o Vitamins are organic compounds and vital nutrients that an organism requires in limited amounts. o They cannot be produced by the body. o Fat-soluble vitamins are stored in the body for long periods of time. o Pose greater risk of toxicity than water-soluble vitamins o Vitamins A, D, E, K Hormones o Hormones are chemical messengers that are secreted directly into the blood, which carries them to organs and tissues of the body to exert their functions. o Cholesterol is the starting material for the synthesis of steroid hormones. o Adrenocorticoid hormones o Sex hormones Ketone Bodies o Ketone bodies serve as an energy source for the heart, kidney, and skeletal muscles, thereby preserving the limited glucose for use by the brain. o Produced by the liver from the breakdown of fatty acids during periods of low food intake, carbohydrate restrictive diets, starvation, prolonged intense exercise, or in untreated type 1 diabetes mellitus. Eicosanoids o Eicosanoids are metabolites of arachidonic acid. o Responsible for inflammatory responses, on the intensity and duration of pain and fever, and on reproductive function. o Inhibits gastric acid secretion o Regulates blood pressure through vasodilation or constriction o Inhibits or activates platelet aggregation & thrombosis. o Prostaglandins (PGs) o Thromboxanes (TXs) o Leukotrienes (LTs) o Lipoxins (LXs). DERIVED LIPIDS (PPT) • Steroids o cyclopentanoperhydrophenanthrene nucleus • Cholesterol o Associated with atherosclerosis & heart disease o Biochemical significance ▪ Precursor of bile acids, adrenocortical hormones, sex hormones, Vit. D, cardiac glycosides, sitosterols and alkaloids o Major constituent of the plasma membrane and of plasma lipoproteins o Cholesteryl ester ▪ – OH at 3 position is esterified with long chain fatty acid ▪ Occurs in animals but not in bacteria LESSON 5 - DERIVED LIPIDS DERIVED LIPIDS • • • Steroids o Steroids are a group of lipids whose carbon skeletons contain several fused rings: Sterols o Also known as steroid alcohol o Occur naturally in plants, animals, and fungi o Plant sterols have cholesterol-lowering properties o Cholesterol o Precursor for vitamins and hormones o Elevated levels of cholesterol in the bloodstream lead to coronary artery disease, heart attack, etc. o Transported through the bloodstream by lipoproteins. Bile Salts o Bile salts are oxidation products of cholesterol. o Bile salts are powerful detergents. o Responsible for fat emulsification o The secretion of bile salts and cholesterol into the bile by the liver is the only mechanism by which cholesterol is excreted. • • Ergosterol o Precursor of vitamin D2 o Occurs in plants and yeast o It is turned into viosterol by UV light, and is then converted into ergocalciferol (a form of Vitamin D) o Acquires antirachitic properties when irradiated with UV light o A component of fungal cell membranes, serving the same function that cholesterol serves in animal cells Polyprenoids o Not steroids, but synthesized like cholesterol o Ubiquinone- participates in respiratory chain in mitochondrion o Dolichol - takes part in glycoprotein synthesis by transferring carbohydrate residues to asparagine residues of polypeptide o Isoprenoid – rubber, camphor, fat soluble- Vit A, D, E & K and -carotene (provitamin A) Bile Salts • Hormones • • Ketone Bodies • Eicosanoids o Derived from eicosa (20 carbon) polyenoic fatty acids o Arachidonic acid is the major precursors ▪ Prostanoids ▪ Leukotrienes (LTs ) ▪ Lipoxins (LXs) Prostanoids o Are part of a family of biologically active lipids derived from the twenty-carbon essential fatty acids or eicosanoids o Relates to the products of the cyclooxygenase pathway o Prostanoic acid as the central structural element  Three main groups ▪ Prostaglandins (PGs) ▪ Prostacyclins (PGIs) ▪ Thromboxanes (TXs) • • • Fat-soluble Vitamins • • Prostaglandins o Acts as local hormones o Synthesized from eicosanoic polyunsaturated fatty acids (arachidonic acid) to form cyclopentane ring o PG1 , PG2 , and PG3– numbers are based on the double bonds in the side chain o The letter component identifies the functional groups of the cyclopentane ring ▪ PGE – keto group in 9 position ▪ PGF – hydroxyl group in 9 position Thromboxanes o Cyclopentane ring interrupted with an oxygen atom o The two major thromboxanes are thromboxane A2 and thromboxane B2 o Its role is in clot formation (thrombosis) • Leukotrienes and Lipoxins o Formed via the lipooxygenase pathway o Has three (leukotrienes) to four (lipoxins) conjugated double bonds o Leukotrienes - a proinflammatory agents and causes bronchoconstriction, thus play a part in asthma ▪ Common leukotriene inhibitors • Zyflo – Zileuton • Accolate – Zarfirlukast • Singulair - Montelukast