Lipids. Polar bears have a large reserve of lipids.

Chapter 28 Lipids Polar bears have a large reserve of lipids. Introduction to General, Organic, and Biochemistry, 10e John Wiley & Sons, Inc Morris Hein, Scott Pattison, and Susan Arena

Course 28.1 Lipids: Hydrophobic Molecules 28.2 Classification of Lipids 28.3 Simple Lipids 28.4 Fats in Metabolism 28.5 Compound Lipids 28.6 Steroids 28.7 Hydrophobic Lipids and Biology Chapter 28 Summary 2

Lipids: Hydrophobic Molecules Lipids are water-insoluble substances that have several important biological functions that are related to how lipids are classified. Lipids interact weakly with water molecules because they are composed primarily of nonpolar alkyl groups. Lipids are classified as hydrophobic ( water fearing ) to designate their inability to interact effectively with water or their strong tendency to move away from water. 3

Lipids: Hydrophobic Molecules Fatty acids are common components of lipids. As fatty acids get larger, the water solubility of the fatty acid decreases dramatically as shown on the next slide... 4

Lipids: Hydrophobic Molecules 5

Your Turn! What characteristic do all lipids have in common? 6

Your Turn! What characteristic do all lipids have in common? All lipids are insoluble in water. 7

Your Turn! Which fatty acid would you predict to have the lowest melting point? O O CH 3 CH 2 CH 2 C OH CH 3 CH 2 CH 2 CH 2 CH 2 C OH 8

Your Turn! Which fatty acid would you predict to have the lowest melting point? O O CH 3 CH 2 CH 2 C OH CH 3 CH 2 CH 2 CH 2 CH 2 C OH m.p. = -7.9 o C m.p. = -3.4 o C Both fatty acids are saturated. The fatty acid with the fewest number of carbon atoms should have the lowest melting point. 9

Classification of Lipids Lipids molecules are relatively large and nonpolar. Yet, within this broad description, lipid structures vary markedly. Lipids can be classified in four categories which recognize major structural similarities. Simple lipids Compound lipids Steroids Miscellaneous lipids 10

Simple Lipids The simple lipids include fats, oils, and waxes. These simple lipids are derivatives of lipid-like substances call fatty acids. Fatty acids are long-chain carboxylic acids (generally greater than about 12 carbons) that have no solubility in water. The hydrophilic -COOH group is referred to as a polar head and the hydrophobic hydrocarbon portion is referred to as a nonpolar tail. 11

Simple Lipids Fats and waxes are solids due to a higher composition of saturated fatty acids while oils are liquids due to a higher composition of unsaturated fatty acids. Table 28.1 on the next slide lists properties of saturated and unsaturated fatty acids separately. Notice how unsaturated fatty acids generally have lower melting points than saturated fatty acids. Lipids prepared from fatty acids with lower melting points tend to be liquids instead of solids at room temperature. 12

Simple Lipids 13

Simple Lipids Unsaturated fatty acids exist as cis and trans isomers. The cis isomer is more prevalent in nature. The cis and trans isomers of oleic acid are shown on the next slide. Oleic acid is an unsaturated fatty acid. The cis isomer has a bent structure which prevents close stacking resulting in a compound that resists solidification. 14

Simple Lipids 15

Your Turn! Draw the cis and trans isomers of palmitoleic acid. CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 7 COOH. 16

Your Turn! Draw the cis and trans isomers of palmitoleic acid. CH 3 (CH 2 ) 5 CH=CH(CH 2 ) 7 COOH. H C C H H trans-isomer H C C cis-isomer 17

Simple Lipids Certain fatty acids, as well as other lipids, are biochemical precursors of several classes of hormones. For example, ω-6 (omega-6) and ω-3 fatty acids are used to make hormones, the most common of which are the eicosanoids. These hormones are derived from fatty acids with 20 carbon atoms, either the ω-6 (arachidonic acid) or the ω-3 (eicosapentaenoic acid). 18

Simple Lipids Omega (ω) is the last letter in the Greek alphabet. Correspondingly, the last carbon atom in a carbon chain of a compound is often referred to as the omega carbon. In reference to unsaturated carboxylic acids, omega plus a number (e.g., ω-3) indicates the location of the first carbon carbon double bond, counting from the omega carbon. 19

Simple Lipids So for example arachidonic acid is an ω-6 fatty acid because the first double bond from the last carbon atom is on the sixth carbon atom. arachidonic acid COOH 6 5 4 3 2 CH 3 1 20

Simple Lipids Examples of eicosanoids are: Thromboxanes Prostacyclins Prostaglandins Leukotrienenes The synthesis of eicosanoids from arachidonic acid is shown on the next slide... 21

22 Chapter

Simple Lipids Eicosanoids are hormones and coordinate various cellular responses. Some are involved with blood clotting as they can cause platelet aggregation while others trigger an increase in body temperature. Some eicosanoids coordinate HCl and mucous secretion by the stomach lining and constriction of the bronchial tubes in the lungs. 23

Simple Lipids Some eicosanoids stimulate and attract white cells, while other eicosanoids cause the white cells to disperse. Eicosanoids can also cause vasodilation as well as vasoconstriction. 24

Simple Lipids Many drugs control one or more of the physiological effects produced by the eicosanoids. For example, aspirin is a nonsteroidal anti-inflammatory drug (and NSAID) that blocks the oxidation of arachidonic acid which in turn prevents the formation of prostaglandins and thromboxanes. 25

Simple Lipids Fats and oils are triester derivatives of glycerol and three fatty acid molecules as shown below. Because there are three ester groups per glycerol, these lipids are called triacylglycerols or triglycerides. The fatty acids have carbon chains with 14-18 carbon atoms. 26

Simple Lipids Triglycerides are prepared by the reaction of a glycerol molecule and three fatty acid molecules. The fatty acid molecules can be saturated or unsaturated. 27

Simple Lipids Waxes are esters of high-molar-mass fatty acids and highmolar-mass alcohols. They have the general formula shown below in which the alcohol (ROH) contributes up to about 30 carbons. 28

Simple Lipids Waxes are very large molecules with almost no polar groups. They represent one of the most hydrophobic classes of lipids. Their extreme water insolubility allows waxes to serve a protective function. Leaves, feathers, fruit, and fur are often naturally coated with wax. 29

Simple Lipids An important biological function of a wax is to act as a protective coating. The shine on these leaves is due to a thick protective wax coating. 30

Your Turn! Write the formula for a wax formed from palmitic acid [CH 3 (CH 2 ) 14 COOH] and 1-hexacosanol [CH 3 (CH 2 ) 24 CH 2 OH]. 31

Your Turn! Write the formula for a wax formed from palmitic acid [CH 3 (CH 2 ) 14 COOH] and 1-hexacosanol [CH 3 (CH 2 ) 24 CH 2 OH]. palmitic acid portion O O 1-hexacosanol portion As with all waxes, this wax is an ester. 32

Your Turn! What is the correct classification of the fatty acid shown below? ω-3 ω-6 CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH 2 ) 7 COOH 33

Your Turn! What is the correct classification of the fatty acid shown below? ω-3 ω-6 CH 3 (CH 2 ) 4 CH=CHCH 2 CH=CH(CH 2 ) 7 COOH The double bond is attached to the sixth carbon from the end of the molecule furthest from the carboxyl group. This is an ω-6 fatty acid. 34

Fats in Metabolism Fats are an important food source for humans and normally account for about 25 50% of our caloric intake. Fats are an especially good source of metabolic energy. Most metabolic energy is derived from carbon oxidation. When oxidized to carbon dioxide and water, fats supply about 40 kj per gram (9.5 kcal/g), which is more than twice the amount obtained from carbohydrates or proteins. 35

Fats in Metabolism Fats are what our bodies prefer when storing energy reserves. These reserves are in the form of triacylglycereols in fatty tissue. On average, this tissue stores about two to three weeks worth of energy. 36

Your Turn! The carbohydrate glucose (C 6 H 12 O 6 ) and the fatty acid capric acid (C 9 H 19 COOH) have similar molecular weights. Recall that most metabolic energy is derived from carbon oxidation. Using these two molecules as examples, why does fat supply more energy than an equivalent amount of carbohydrate? 37

Your Turn! The carbohydrate glucose (C 6 H 12 O 6 ) and the fatty acid capric acid (C 9 H 19 COOH) have similar molecular weights. Recall that most metabolic energy is derived from carbon oxidation. Using these two molecules as examples, why does fat supply more energy than an equivalent amount of carbohydrate? Fats are about 75% carbon by mass as compared to about 40% for carbohydrates. In addition fats have a lower degree of carbon oxidation when compared to carbohydrates which results in higher energy yields 38 when fats are oxidized.

Compound Lipids There are three broad categories of compound lipids. Phospholipids Sphingolipids Glycolipids 39

Compound Lipids The phospholipids are a group of compounds that yield one or more fatty acid molecules, a phosphate group, and usually a nitrogenous base upon hydrolysis. In contrast to the triacylglycerols, phospholipids have a hydrophilic end that interacts with water. 40

Compound Lipids Phospholipids are one of the most important membrane components. They are also involved in the metabolism of other lipids and nonlipids. Three categories of phospholipids are phosphatidic acids, phosphatidylcholines, and phosphatidylethanolamines. 41

Compound Lipids Phosphatidic acids are glyceryl esters of fatty acids and phosphoric acid. The phosphatidic acids are important intermediates in the synthesis of triacylglycerols and other phospholipids. 42

Compound Lipids Phosphatidylcholines (lecithins) are glyceryl esters of fatty acids, phosphoric acid, and choline. 43

Compound Lipids The single most important biological function for phosphatidylcholine is as a membrane component which makes up between 10 and 20% of many membranes. 44

Compound Lipids Another important constituent of biological membranes is the phosphatidylethanolamines (cephalins). These lipids are glyceryl esters of fatty acids, phosphoric acid, and ethanolamine (HOCH 2 CH 2 NH 2 ). 45

Compound Lipids Sphingolipids are another type of compound lipid that, when hydrolyzed, yield: a hydrophilic group (either phosphate and choline or a carbohydrate) a long-chain fatty acid (18 26 carbons) sphingosine (an unsaturated amino alcohol) 46

Compound Lipids The similarities between sphingosine and glycerol are shown in the structures below. 47

Compound Lipids Sphingolipids are common membrane components because they have both hydrophobic and hydrophilic character. Sphingomyelins are found in the myelin sheath membranes that surround nerves. 48

Compound Lipids Glycolipids are a third type of compound lipid. These compounds that contain a carbohydrate group. The two most important classes of glycolipids are cerebrosides and gangliosides. These substances are found mainly in cell membranes of nerve and brain tissue. 49

Compound Lipids A cerebroside may contain either D-galactose or D- glucose. The following formula of a galactocerebroside shows the typical structure of cerebrosides. 50

Your Turn! What is the classification of the following lipid? 51

Your Turn! What is the classification of the following lipid? This lipid is an example of a phospholipid and more specifically a phosphatidylethanolamine. 52

Your Turn! What is the classification of the following lipid? 53

Your Turn! What is the classification of the following lipid? This molecule is a glycolipid. 54

Steroids Steroids are compounds that have the steroid nucleus, which consists of four fused carbocyclic rings. This nucleus contains 17 carbon atoms in one five-membered ring and three six-membered rings. 55

Steroids Modifications of this nucleus that occur in the various steroid compounds include, for example, added side alkyl chains, hydroxyl groups, carbonyl groups, and ring double bonds. Steroids are closely related in structure but are highly diverse in function... 56

Steroids For example: Cholesterol, the most abundant steroid in the body, is widely distributed in all cells and serves as a major membrane component. Bile salts aid in the digestion of fats. Ergosterol, a yeast steroid, is converted to vitamin D by ultraviolet radiation. 57

Steroids Digitalis and related substances called cardiac glycosides are potent heart drugs. The adrenal cortex hormones are involved in metabolism. The sex hormones. 58

Steroids Cholesterol is the parent steroid compound from which the steroid hormones are synthesized. In this process cholesterol is converted to progesterone, a compound that helps control the menstrual cycle and pregnancy. This hormone is also the parent compound from which testosterone and the adrenal corticosteroids are produced. 59

Steroids Cholesterol is also used to build cell membranes, many of which contain about 25% by mass of this steroid. 60

Your Turn! Identify the functional groups in cortisone. CH 2 OH O CH 3 C O CH 3 O 61

Your Turn! Identify the functional groups in cortisone. hydroxyl group CH 2 OH carbonyl group O CH 3 C O carbonyl group CH 3 O carbonyl group carbon-carbon double bond 62

Hydrophobic Lipids and Biology The hydrophobic nature of lipids has many important biological consequences. The water insolubility of lipids results in: lipid aggregation that causes atherosclerosis lipid aggregation that forms biological membranes A lipid is in a hostile environment when it is surrounded by water. Lipid molecules aggregate to minimize their contact with water when in water. 63

Hydrophobic Lipids and Biology The hydrophilic part of lipid molecules is attracted to water and forms an interface with it, but the hydrophobic part distances itself from water molecules. Complex lipids such as phospholipids and sphingolipids have two hydrophobic alkyl groups. 64

Hydrophobic Lipids and Biology Complex lipids form liposomes in aqueous mixtures. Liposomes are bounded by two layers of lipid. The hydrophobic alkyl chains are covered by hydrophilic groups on both the liposome s inside and outside. Liposomes have a water core as shown below. 65

Hydrophobic Lipids and Biology Atherosclerosis is a metabolic disease that leads to deposits of cholesterol and other lipids on the inner walls of the arteries. Blood pressure increases as the heart works harder to pump sufficient blood through the narrowed passages, which may eventually lead to heart attack. Plaque formation begins because of a lipid s natural tendency to aggregate. 66

Hydrophobic Lipids and Biology Improper transport of cholesterol through the blood contributes to atherosclerosis. Cholesterol (and other lipids) must be packaged for transport because lipids aggregate in the aqueous bloodstream. Lipids are packaged in particles called lipoproteins. 67

Hydrophobic Lipids and Biology The main types of lipoproteins are VLDL (very-lowdensity lipoprotein), LDL (low-density lipoprotein) and HDL (high-density lipoprotein). The lipid distribution system through the bloodstream using these lipoproteins is shown on the following slide... 68

Hydrophobic Lipids and Biology 69

Hydrophobic Lipids and Biology Biological membranes are thin, semipermeable cellular barriers. The general function of these barriers is to exclude dangerous chemicals from the cell while allowing nutrients to enter. Because almost all the dangerous chemicals, nutrients, and special molecules are water soluble, the membranes can act as effective barriers only if they impede the movement of hydrophilic (water-soluble) molecules. 70

Hydrophobic Lipids and Biology The hydrophobic interior of the membrane provides the necessary barrier while the hydrophilic exterior interacts with the aqueous environment. 71

Hydrophobic Lipids and Biology Membrane lipids naturally aggregate to form lipid bilayers. A lipid bilayer is composed of two adjoining layers of lipid molecules aligned so that their hydrophobic portions form the bilayer interior while their hydrophilic portions form the bilayer exterior. 72

Hydrophobic Lipids and Biology All known cells in today s world need a membrane that is more complicated than a simple lipid bilayer. A membrane must function as more than just a barrier. Tasks such as passing molecules from one side of a bilayer to the other are an essential part of life. Proteins in the fluid bilayer solve this dilemma. They allow specific molecular transport through the hydrophobic interior. 73

Hydrophobic Lipids and Biology If the protein helps transport without using energy, the process is called facilitated diffusion. Energy-requiring transport is termed active transport. 74

Hydrophobic Lipids and Biology A complete cellular membrane must have both lipid and protein. A typical membrane includes about 60% protein, 25% phospholipid, 10% cholesterol, and 5% sphingolipid. The fluid lipid bilayer is studded with many solid proteins. The proteins form a random pattern on the outer surface of the oily lipid. This general membrane is called the fluid-mosaic model which is shown on the next slide... 75

Hydrophobic Lipids and Biology 76

Hydrophobic Lipids and Biology Which statement best describes the composition of a biological membrane? Hydrophobic exterior and hydrophilic interior Hydrophilic exterior and hydrophobic interior Hydrophilic exterior and interior Hydrophobic exterior and interior 77

Hydrophobic Lipids and Biology Which statement best describes the composition of a biological membrane? Hydrophobic exterior and hydrophilic interior Hydrophilic exterior and hydrophobic interior Hydrophilic exterior and interior Hydrophobic exterior and interior Biological membranes have hydrophilic exteriors and hydrophilic interiors. 78

Chapter 28 Summary Lipids are water-insoluble, oily, or greasy biochemicals. All lipids are relatively large and nonpolar, yet lipid structures may differ markedly. Simple lipids are esters of fatty acids and alcohols. Fats and oils are esters of fatty acids and glycerol. Waxes are esters of fatty acids and high-molar-mass alcohols. 79

Chapter 28 Summary Compound lipids are composed of fatty acid esters and other components. Phospholipids yield a phosphate and a nitrogencontaining base as well as glycerol and fatty acids upon hydrolysis. Sphingolipids yield an unsaturated amino alcohol (sphingosine) and a carbohydrate or phosphate and nitrogen base in addition to a fatty acid upon hydrolysis. 80

Chapter 28 Summary Glycolipids yield sphingosine and a carbohydrate as well as a fatty acid upon hydrolysis. Steroids posses the steroid nucleus containing 17 carbon atoms. Miscellaneous lipids include lipoproteins. 81

Chapter 28 Summary Fatty acids, which form part of most lipids, are carboxylic acids with long, hydrophobic carbon chains. Common fatty acids are straight-chain compounds with an even number of carbons. Unsaturated (double bond containing) fatty acids are commonly cis isomers. Omega-3 and omega-6 fatty acids are essential in human diets. The eicosanoids are formed by oxidizing either 82 omega-3 or omega-6 fatty acids.

Chapter 28 Summary Fats and oils are esters of glycerol and long carbon chain fatty acids. Waxes are esters of fatty acids and a high-molar-mass alcohol (up to about 30 carbons long). Fats are a rich source of metabolic energy. They contain a high percentage of carbon, whose oxidation releases energy. Fats are our primary energy-storage molecules. 83

Chapter 28 Summary The phospholipids are a group of compounds that yield one or more fatty acid molecules, a phosphate group, and a nitrogenous base upon hydrolysis. Phospholipids combine hydrophobic and hydrophilic properties, essential features of membrane lipids. Sphingolipids are compounds that, when hydrolyzed, yield a hydrophilic group, a fatty acid, and sphingosine. 84

Chapter 28 Summary Glycolipids are sphingolipids that contain carbohydrates. Steroids are compounds that have the steroid nucleus. The combined hydrophobic and hydrophilic character of some lipids causes them to aggregate into specific structures when placed in water. Atherosclerosis is a metabolic disease in which fatty material (plaque) is deposited on the inner walls of arteries. 85

Chapter 28 Summary Improper transport of cholesterol through the blood system contributes to atherosclerosis. Lipoproteins (specific protein-lipid aggregates) transport lipids through the blood. A lipid bilayer is composed of two adjoining layers of compound lipid molecules. Proteins aid passage of molecules through a lipid bilayer. 86