Biochemistry 6 - Lipids -1 PDF

BIOMOLECULES Proteins Carbohydrates Lipids Nucleic acids Lipids Lipids are essential components of all living organisms Lipids are organic molecules essential for life that are composed mostly of C, H, O They naturally occur in most plants, animals, and microorganisms and...

BIOMOLECULES Proteins Carbohydrates Lipids Nucleic acids Lipids Lipids are essential components of all living organisms Lipids are organic molecules essential for life that are composed mostly of C, H, O They naturally occur in most plants, animals, and microorganisms and are used as cell membrane components, energy storage molecules, insulation, and hormones Lipids are a heterogeneous group of organic compounds that are insoluble in water and soluble in non-polar organic solvents They are hydrophobic (nonpolar) or amphipathic (containing both nonpolar and polar regions) Classification of lipids Unlike polysaccharides and proteins, lipids are not polymers—they lack a repeating monomeric unit. They can be classified according to their similarities in their molecular structures Three major subclasses are recognised: Simple lipids: (a) Fats and oils which yield fatty acids and glycerol upon hydrolysis (b) Waxes, which yield fatty acids and long-chain alcohols upon hydrolysis Compound lipids: (a) Phospholipids, which yield fatty acids, glycerol, phosphoric acid and a nitrogen- containing alcohol upon hydrolysis (b) Glycolipids, which yield fatty acids, sphingosine or glycerol, and a carbohydrate upon hydrolysis (c) Sphingolipids, which yield fatty acids, sphingosine, phosphoric acid, and an alcohol component upon hydrolysis Steroids: Compounds containing a phenanthrene structure that are quite different from lipids made up of fatty acid; they are characterised by having a carbon skeleton with four fused rings Classification of lipids Fatty Acids - In the carboxylic acid family Waxes - Fatty Acids + Alcohols Triglycerides - 3 Fatty acids + glycerol Phospholipids and glycolipids - 2 fatty acids + glycerol + phosphate + X Steroids - Derivatives of cholesterol Eicosanoids - Derivatives of the Fatty acid arachidonic acid Membranes - Formed from phospholipids and glycolipids Classification of lipids Physical properties of lipids Lipids may be either liquids or non-crystalline solids at room temperature Contrary to popular belief, pure fats and oils are colourless, odourless, and tasteless The characteristic colours, odours, and flavours associated with lipids are imparted to them by foreign substances that have been absorbed by the lipid and are soluble in them; (For example, the yellow colour of butter is due to the presence of the pigment carotene; the taste of butter is a result of two compounds, diacetyl and 3-hydroxy-2-butanone that are produced by bacteria in the ripening of the cream) Fats and oils are lighter than water and they are poor conductors of heat and electricity and, therefore, serve as excellent insulators for the body Key principles of fatty acids FA are water-insoluble hydrocarbons used for cellular energy storage FA are highly reduced and thus provide a rich source of stored chemical energy for cells Storage of hydrophobic fats as triacylglycerols is highly efficient because water is not needed to hydrate the stored fat Fatty Acids Fatty acids are carboxylic acids with hydrocarbon chains ranging from 4 to 36 carbons long (typically contain between 12 and 20 carbons) Fatty acids contain a carboxylic acid group This should make them quite polar However, they also contain a long hydrocarbon tail Which overall, makes them nonpolar nonpolar polar Fatty acids In some fatty acids, this chain is fully saturated (contains no double bonds) In others, the chain contains one or more double bonds (is unsaturated) Standard nomenclature: (Part a) assigns the number 1 to the carboxyl carbon (C- A few contain three-carbon rings, 1), and  to the carbon next to it. The position of any hydroxyl groups, or methyl-group double bonds is indicated by ∆ followed by a superscript number indicating the lower-numbered branches carbon in the double bond. For polyunsaturated fatty acids, an alternate convention Two conventions for naming fatty numbers the carbons in the opposite direction, acids are illustrated by the figure assigning the number 1 to the methyl carbon at the other end of the chain (Part b). This carbon is also designated  (omega, the last letter in the Greek alphabet). The positions of the double bonds are indicated relative to the  carbon, as in -3 and -6 fatty acids In the fully saturated fatty acids, free rotation around each carbon-carbon bond gives the hydrocarbon chain great flexibility The most stable conformation is the fully extended form as the molecules can pack together tightly in nearly crystalline arrays, with atoms all along their lengths in van der Waals contact with the atoms of neighboring molecules In unsaturated fatty acids, a cis double bond forces a kink in the hydrocarbon chain Fatty acids with one or several such kinks cannot pack together as tightly as fully saturated fatty acids, and their interactions with each other are, therefore weaker Because less thermal energy is needed to disorder these poorly ordered arrays of unsaturated fatty acids, they have markedly lower melting points than saturated fatty acids of the same chain length Common Saturated Fatty Acids Common Unsaturated Fatty Acids Linoleic acid is the precursor of arachidonic acid, which is used for synthesis of eicosanoids (e.g., prostaglandins) -Linolenic acid is the precursor of the -3 fatty acids eicosapentaenoic Essential! acid [EPA] and docosahexaenoic acid [DHA] which are important fatty acids found in membranes of the retina, for example -3 fatty acids are important components of a heart-healthy diet Fatty Acids saturated monounsaturated polyunsaturated polyunsaturated Common Fatty Acids and their sources Linolenic acid is one of the omega-3 fatty acids Physical properties of fatty acids The physical properties of the fatty acids, and of compounds that contain them, are largely determined by the length and degree of unsaturation of their hydrocarbon chains The hydrocarbon chain accounts for the poor solubility of fatty acids in water The longer the fatty acid chain and the fewer the double bonds, the lower is the solubility in water The carboxylic acid group is polar (and ionized at neutral pH) and accounts for the slight solubility of short-chain fatty acids in water Melting points are also strongly influenced by the length and degree of unsaturation of the hydrocarbon chain At 25˚C, the saturated fatty acids from 12:0 to 24:0 have a waxy consistency, whereas unsaturated fatty acids of these lengths are oily liquids. The differences in melting points is due to differences in the packing abilities of the fatty acid chains Fatty Acids Melting points for saturated fatty acids: Melting Temperature {°C} No. of Carbons Fatty Acids Normally the double bonds are cis This lowers the melting points for fatty acids containing double bonds. Melting Temperature {°C} No. of Double Bonds Melting points of common dietary fats From F to C estimate - 30 = /2  Simple lipids (fats and oils) Fats and oils are the most abundant lipids found in nature Both types of compounds are called triacylglycerols because they are esters composed of three fatty acids joined to glycerol, a trihydroxy alcohol Further classification of triacylglycerols is made on the basis of their physical states at room temperature It is customary to call a lipid a fat if it is solid at 25°C, and an oil if it is a liquid at the same temperature (These differences in melting points reflect differences in the degree of unsaturation of the constituent fatty acids) Lipids obtained from animal sources are usually solids whereas oils are generally of plant origin Therefore, we commonly speak of animal fats and vegetable oils Structure of Triacylglycerols The simplest lipids constructed from fatty acids are the triacylglycerols (a.k.a., triglycerides, fats, neutral fats) Triacylglycerols are composed of three fatty acids each in ester linkage with a single glycerol molecule Most naturally occurring triacylglycerols are mixed, and contain two or more different fatty acids Because the polar hydroxyls of glycerol and the polar carboxylates of the fatty acids are bound in ester linkages, triacylglycerols are very nonpolar molecules that are essentially insoluble in water Lipids have lower specific gravities than water which explains why mixtures of triacylglycerols and water have two phases in which the triacylglycerol phase floats on top of the water (as in oil-and-vinegar salad dressing). Esters Distinguished by a functional group that contains the element oxygen Esters Chemically, esters can be synthesize by reacting a carboxylic acid with and alcohol: O CH3 CH2 C O CH2 CH3 Carboxylic Alcohol acid part part Ethyl propanoate Fatty Acid Compositions of Food Fats Most natural fats, such as those in vegetable oils, dairy products, and animal fat, are complex mixtures of simple and mixed triacylglycerols These contain a variety of fatty acids differing in chain length and degree of saturation The melting points of these fats and hence their physical state at room temperature are a direct function of their fatty acid compositions Olive oil has a high proportion of long-chain (C16 and C18) unsaturated fatty acids, which accounts for its liquid state at 25˚C The higher proportion of long-chain (C16 and C18) saturated fatty acids in butter increases its melting point, so butter is a soft solid at room temperature Beef fat, with an even higher proportion of long-chain saturated fatty acids is a hard solid Trans Fatty Acids in Foods When lipid-rich foods are exposed too long to the oxygen in air, their unsaturated fatty acids may react leading to formation of aldehydes and ketones To improve the shelf-life of vegetable oils used in cooking, and to increase their stability at the high temperatures used in deep-frying, commercial vegetable oils are altered by partial hydrogenation This process converts many of the cis double bonds in the fatty acids to single bonds and increases the melting temperature of the oils so they are more nearly solid at room temperature This process is used to produce margarine from vegetable oils Partial hydrogenation has another, undesirable effect: some cis-double bonds are converted to trans-double bonds Commercial Hydrogenation of Fatty Acids H H H H H R partial H2 catalyst C C R C C R + C C R R H H R H ‘cis’ ‘trans’ unsaturated saturated unsaturated natural natural unnatural good bad? bad An unwanted byproduct Trans fats increase the level of Low density lipoprotein (LDL) Thus they are deemed to be “heart unhealthy” since LDL tends to deposit cholesterol in the arteries rather than transport it (as does HDL) to cells for use in cell membrane construction (?) There is now strong evidence that dietary intake of trans fatty acids (trans fats) increases the incidence of cardiovascular disease. This may be due in part to the fact that trans fats raise LDL levels and lower HDL levels. Many fast foods and other prepared foods are deep-fried in partially hydrogenated vegetable oils and therefore contain high levels of trans fatty acids (Table 10-2). The deleterious effects of trans fats occur at intakes of 2 to 7 g/day Lipoproteins Lipoproteins are used to transport the water insoluble lipids such as triglycerides, phospholipids and cholesterol, in the blood. Lipoproteins contain lipids and proteins. They include: Chylomicrons transport primarily triglycerides from the digestive track. LDLs (low density lipoproteins) transport cholesterol, triglycerides and phospholipids from the liver to other tissues. HDLs (high density lipoproteins) transport cholesterol and phospholipids back to the liver. Triglycerides Triglycerides are a storage form of fatty acids in mammals. Often when blood tests are done, they measure your triglyceride levels. High triglyceride levels in the blood are a risk indicator for atherosclerosis. *American Heart Association Fat Stores in Cells In most eukaryotic cells, triacylglycerols form microscopic, oily droplets in the aqueous cytosol, serving as metabolic fuel In vertebrates, specialized cells called adipocytes or fat cells, store large amounts of triacylglycerols as fat droplets that nearly fill the cell (upper Figure) Triacylglycerols are also stored in the seeds of many types of plants, providing energy and biosynthetic precursors during seed germination (lower Figure) Adipocytes and germinating seeds contain enzymes known as lipases that catalyze the hydrolysis of stored triacylglycerols, releasing fatty acids for export to sites where they are required as fuel Triacylglycerols contain more energy per gram than do polysaccharides such as glycogen (9 cal/g vs 4 cal/g) In addition, they are unhydrated, and the organism does not have to carry extra weight in the form of hydrated water as with stored polysaccharides In some animals, such as seals, penguins, and bears, fat stores under the skin also serve as insulation against cold temperatures Adipose tissue - fat Adipose tissue forms cushioning shields around our major organs, protecting them against damage from physical shock and provides insulation to our bodies, guarding against a rapid loss of body heat to the external environment Fats carry the flavours and vitamins of many of our foods, although fats have no flavours of their own, eg. carrying vitamins A, D, E and K from our foods to our tissues Fatty acids form not only the triglycerides but other compounds as well, including such vital classes as prostaglandins and phospholipids  Fat = Essential Energy Most of our long term energy supplies operates via the formation, storage and metabolism of body fat (triglycerides). Short term energy storage, from one meal to another, occurs through a starch-like substance called glycogen(a carbohydrate) Waxes Biological waxes are esters of long-chain (C14 to C36) saturated and unsaturated fatty acids with long-chain (C16 to C30) alcohols Waxes are esters - carboxylic acids react with alcohols to from esters  The structure of the wax, triacontanoylpalmitate, which is the major component of the beeswax used in honeycomb construction The melting points of waxes (60 to 100˚C) are generally higher than those of triacylglycerols In plankton, waxes are the chief storage form of metabolic fuel For many other organisms, waxes function as water-repelents Biological waxes also find a variety of applications in the pharmaceutical, cosmetic, and other industries, where they are used in the manufacture of lotions, ointments, and polishes Waxes Waxes are very hydrophobic and are used by plants and animals for protective, water-proof coatings Membrane lipids All of the lipid types shown have either glycerol or sphingosine as the backbone (light red shading), to which are attached one or more long- chain alkyl groups (yellow) and a polar head group (blue) Phospholipids and Glycolipids Phospholipids and Glycolipids are the stuff that biological membranes are made of These molecules are highly amphipathic, and when mixed with water spontaneously form membranes that are described as lipid bilayers Phospholipids Phosphospholipids There are two types of phospholipids Glycerophospholipids 38 Phospholipids Phosphospholipids There a are two types of phospholipids Sphingolipids 39 Glycerophospholipids Glycerophospholipids have a structure similar to triglycerides, with one of the fatty acids replaced with a phosphate. phosphoester 40 bonds Sphingolipids The sphingolipids function similarly to the glycerophospholipids, but structurally they are different There is not glycerol core The glycerol and one of the fatty acids found in glycerophospholipids is replaced with a molecule called sphingosine The sphingolipids are found in the myelin membranes that insulate the nerve cells Glycolipids Some sphingolipids use sugars for the alcohol portion of the molecule These are called glycolipids The gangliosides are glycosphingolipids containing complex oligosaccharide chains with sialic acid residues These lipids are important for cell-cell recognition Other glycosphingolipids, the globosides, contain oligosaccharide chains that serve as the blood group antigens Cerebrosides important for insulation of nerve fibers Differences Between Gangliosides, Globosides, and Cerebrosides Phospholipids Phospholipids are used commercially as emulsifying agents An emulsifying agent stabilizes an emulsion An emulsion is a colloidal suspension of one liquid in another An example is mayonnaise, which is a colloidal suspension of oil and water Lecithin, which is another name for the phospholipid phosphatidylcholine, is used as an emulsifying agent in mayonnaise and other prepared foods Found in egg yolks, soy beans Sterols - cholesterol Sterols are structural lipids present in the membranes of most eukaryotic cells Sterols such as cholesterol, consist of a rigid steroid nucleus containing four fused rings, an alkyl side chain of 8 carbons, and a sole hydrophilic hydroxyl group attached to C-3 of ring A The steroid nucleus is nearly planar, and the molecule packs well with the acyl chains of membrane glycerophospholipids and sphingolipids Cholesterol is only found in animals Besides being used to synthesize the other steroids, cholesterol is dissolved in membranes to keep them fluid. Plants use the alternative strategy of using polyunsaturated fatty acids to make their phospholipids Sterols and their roles In addition to their roles as membrane constituents, sterols serve as precursors for a variety of products with specific biological functions Steroid hormones, for example, are potent biological signaling molecules that regulate gene expression Vitamin D, which helps regulate calcium metabolism, is also derived from cholesterol Bile acids are polar derivatives of cholesterol made in the liver, that act as detergents in the intestine, emulsifying dietary fats to make them more accessible to digestive enzymes Steroids Comprise of a group of cyclical organic compounds whose basis is a characteristic arrangement of 17 carbon atoms in a four-ring structure linked together from three 6-carbon rings followed by a 5- carbon ring and 8-carbon side chain on carbon 17 Classification Again there are different means of classifying the steroids Here, I present one based on the type of substituent group at C-17, i.e., group R 1. Sterols – R is an aliphatic side chain, containing usually one or more hydroxyl groups 2. Sex hormones – R bears a ketonic or hydroxyl group and mostly possess a two carbon side chain 3. Cardiac glycoside – R is a lactone ring (contains sugar) 4. Bile acids – R is essentially a five-carbon side chain ending with a carboxylic acid 5. Sapongenins – R contains an oxacyclic ring system 49  Steroids Structure: 4 fused Carbon rings examples: cholesterol – Function =control the fluidity of the cell membrane hormones – Function = regulate processes in the body (such as pregnancy) vitamins (A, B, D) – Function = supports metabolism and cell processes Lipids - review Lipids are a heterogeneous group of compounds, including fats, oils, steroids, waxes, and related compounds, which are related more by their physical than by their chemical properties: insolubility in water and solubility in nonpolar solvents Lipids are important in biological systems: they form the cell membrane, provide energy for life and several essential vitamins are lipids Three major subclasses are recognised: simple, compounds and steroids Lipids can be also divided in two major classes: nonsaponifiable lipids and saponifiable lipids Lipids examples Saponifiable vs. non saponifiable lipids A saponifiable lipid contains one or more ester groups allowing it to undergo hydrolysis in the presence of an acid, base, or enzyme A nonsaponifiable lipid cannot be broken up into smaller molecules by hydrolysis Saponification of triglycerides Converts triglycerides into fatty acid salts (soaps) and glycerol The salts of fatty acids are considered amphipathic, meaning they have a part that is very hydrophobic along with a part that is very hydrophilic – -We have discussed how amphipathic molecules form interesting structures when exposed to water before 55 Sodium carboxylates