Chapter 21 Lipids

Lipids Lipids: A heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties. Insoluble in water, but soluble in organic solvents including diethyl ether, dichloromethane, and acetone. Lipids include: Fatty acids, triglycerides, sphingolipids, phosphoacylglycerols, and glycolipids. Lipid-soluble vitamins. Prostaglandins, leukotrienes, and thromboxanes. Cholesterol, steroid hormones, and bile acids.

Triglycerides Triglyceride: A triester of glycerol with three fatty acids. In most triglycerides, two or three different fatty acid components are present. The hydrophobic character is caused by the long hydrocarbon chains. The ester groups, although polar, are buried within a nonpolar environment, which makes triglycerides insoluble in water.

Triglycerides In triglycerides, all three hydroxyl groups of glycerol are esterified with fatty acids.

Fatty Acids The fatty acid components of triglycerides have certain things in common: 1. Practically all are unbranched carboxylic acids. 2. They range in size from about 10 to 20 carbons. 3. They contain an even number of carbon atoms. 4. Apart from the -COOH group, they have no functional groups, except that some have carbon-carbon double bonds. 5. In most fatty acids that have carbon-carbon double bonds, the cis isomers predominate.

Triglycerides The physical properties of triglycerides depend on the fatty acid components. Melting points of fatty acids increases as the number of carbons in the hydrocarbon chains increases and as the number of double bonds decreases. Triglycerides rich in unsaturated fatty acids are generally liquid at room temperature and are called oils Triglycerides rich in saturated fatty acids are generally semisolids or solids at room temperature and are called fats.

Triglycerides Hardening: The reduction of some or all of the carbon-carbon double bonds of an unsaturated triglyceride using H2/transition metal catalyst, which converts a liquid triglyceride to a semisolid. In practice, the degree of hardening is carefully controlled to produce fats of a desired consistency. The resulting fats are sold for kitchen use (Crisco, Spry, Dexo, and others). Margarine and other butter substitutes are produced by partial hydrogenation of polyunsaturated oils derived from corn, cottonseed, peanut, and soybean oils. The hardening process is the source of trans fatty acids (see Chemical Connections 18A).

Triglycerides Saponification: the base-promoted hydrolysis of fats and oils in aqueous NaOH and produces glycerol and a mixture of fatty acid salts called soaps.

Complex Lipids Phospholipids Contain an alcohol, two fatty acids, and a phosphate ester. In glycerophospholipids, the alcohol is glycerol. In sphingolipids, the alcohol is sphingosine. Glycolipids Complex lipids that contain a carbohydrate.

Complex Lipids Figure 21.1 Schematic diagram of simple and complex lipids.

Biological Membranes Complex lipids form the membranes around cells and around small structures within cells. In aqueous solution, complex lipids spontaneously form into a lipid bilayer, with a back-to-back arrangement of lipid monolayers. Polar (hydrophilic) head groups are in contact with the aqueous environment. Nonpolar (hydrophobic) tails are buried within the bilayer and shielded from the aqueous environment. The major force driving the formation of lipid bilayers is hydrophobic interaction. The arrangement of hydrocarbon tails in the interior can be rigid (if rich in saturated fatty acids) or fluid (if rich in unsaturated fatty acids).

Fluid Mosaic Model Figure 21.2 The fluid mosaic model of membranes.

Glycerophospholipids Glycerophospholipids, also called phosphoglycerides are the second most abundant group of naturally occurring lipids. Found almost exclusively in plant and animal membranes, which typically consist of 40% -50% phosphoacylglycerols and 50% - 60% proteins. The most abundant glycerophospholipids are derived from phosphatidic acid, a molecule in which glycerol is esterified with two molecules of fatty acid and one of phosphoric acid. The three most abundant fatty acids in phosphatidic acids are palmitic (16:0), stearic (18:0), and oleic (18:1).

Glycerophospholipids A phosphatidic acid The fatty acid on carbon 2 of glycerol is always unsaturated. Further esterification with a low-molecular-weight alcohol (screen 14) gives a glycerophospholipid.

Glycerophospholipids The structure of glycerophospholipids is very similar to that of fats. The alcohol is glycerol. Two of the three hydroxyl groups are esterified with fatty acids.The third hydroxyl group is esterified with phosphoric acid, which is also esterified with another alcohol.

Glycerophospholipids If the other alcohol is choline, the glycerophospholipid is called a phosphatidylcholine(common name lecithin).

Glycerophospholipids Figure 21.3 Space-filling model of complex lipids in a bilayer. The hydrophobic tails point toward the middle of the bilayer and the hydrophilic heads line both the inner and outer surfaces of the membranes.

Glycerophospholipids Cephalins: Another group of glycerophospholipids in which the additional phosphate ester is provided by either ethanolamine or serine.

Sphingolipids Contain the long-chain aminoalcohol, sphingosine, from which this class of compounds in named. The sphingolipid myelin is found in the coatings of nerve axons.

Glycolipids Glycolipid: a complex lipid that contains carbohydrates and ceramides. The carbohydrate is either glucose or galactose. The cerebrosides are ceramide mono- or oligosaccharides. The following is a glucocerebroside.

Steroids Steroids: A group of plant and animal lipids that contain this tetracyclic ring structure.

Cholesterol Cholesterol is the most abundant steroid in the human body, and also the most important. It is a component in plasma membranes in all animal cells. It is the precursor of all steroid hormones and bile acids.

Steroid Hormones Cholesterol is the starting material for the synthesis of steroid hormones. It is converted first to progesterone and then to both sex hormones and adrenocorticoid hormones.

Lipoproteins Lipoproteins: Carriers of cholesterol. Most lipoproteins contain a core of hydrophobic lipid molecules surrounded by a shell of hydrophilic molecules such as proteins and phospholipids. There are four kinds of lipoproteins. High-density lipoprotein (HDL) (“good cholesterol”), which consists of about 33% protein and 30% cholesterol. Low-density lipoprotein (LDL) (“bad cholesterol”). which contains about 25% protein and 50% cholesterol. Very-low density lipoprotein(VLDL), which carries triglycerides (fats) synthesized by the liver. Chylomicrons, which carry dietary lipids synthesized in the intestines.

Low-Density Lipoprotein Figure 21.5 Low-density lipoprotein.

Cholesterol Transport Transport of cholesterol from the liver starts out as a large VLDL particle. VLDL is carried in the serum. As fat is removed, its density increases and it becomes LDL; LDL stays in the plasma for about 2.5 days. LDL carries cholesterol to cells, where specific LDL receptors bind it. After binding, LDL is taken into cells where enzymes liberate free cholesterol and cholesteryl esters.

Cholesterol Transport High-density lipoproteins (HDL) transport cholesterol from peripheral tissues to the liver and also transfer cholesterol to LDL. While in the serum, free cholesterol in HDL is converted to cholesteryl esters. In the liver, HDL binds to the liver cell surface and transfers its cholesteryl esters to the cell. These esters are used for the synthesis of steroid hormones and bile acids. After HDL has delivered its cholesteryl esters to liver cells, it reenters circulation.

Levels of LDL and HDL Most of the cholesterol is carried by LDL. Normal plasma levels are 175 mg/100 mL. If there are sufficient LDL receptors on the surface of cells, LDL is removed from circulation and its concentration in blood plasma drops. The number of LDL receptors is controlled by a feedback mechanism. When the concentration of cholesterol inside cells is high, the synthesis of LDL receptors is suppressed. In the disease called famelial hypercholesterolemia, there are not enough LDL receptors and plasma levels of cholesterol may be as high as 680 mg/100 mL.

Levels of LDL and HDL These high levels of cholesterol can cause premature atherosclerosis and heart attacks. In general, high LDL means high cholesterol content in the plasma because LDL cannot get into cells. Therefore, high LDL together with low HDL is a symptom of faulty cholesterol transport and a warning of possible atherosclerosis. The serum cholesterol level controls cholesterol synthesis in the liver. When serum cholesterol is high, its synthesis in the liver is low, and vice versa. The commonly used statin drugs inhibit the synthesis of cholesterol by blocking HMG-CoA reductase.

Steroid Hormones Male sex hormones Synthesized in the testes from cholesterol. Responsible for the development of male secondary sex characteristics.

Steroid Hormones Among the synthetic anabolic steroids are:

Steroid Hormones Female sex hormones Synthesized in the ovaries from progesterone. Responsible for the development of female secondary sex characteristics and control of the menstrual cycle.

Steroid Hormones Progesterone-like analogs are used in oral contraceptives:

Glucocorticoid Hormones Synthesized in the adrenal cortex. Regulate metabolism of carbohydrates. Decrease inflammation. Involved in the reaction to stress.

Bile Salts Bile salts are oxidation products of cholesterol. Synthesized in the liver, stored in the gallbladder, and secreted into the intestine where they emulsify dietary fats and aid in their absorption and digestion.

Prostaglandins Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid.

Prostaglandins Prostaglandins are not stored in tissues as such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids in response to specific physiological triggers. one such polyunsaturated fatty acid is arachidonic acid.

Prostaglandins

COX Enzymes The COX (cyclooxygenase) enzyme occurs in two forms: COX-1 catalyzes the normal physiological production of prostaglandins. COX-2 is responsible for the production of prostaglandins in inflammation. When a tissue is injured or damaged, special inflammatory cells invade the injured tissue and interact with resident cells, for example, smooth muscle cells. This interaction activates COX-2 and prostaglandins are synthesized.

Thromboxanes Thromboxanes are also derived from arachidonic acid. Thromboxane A2 induces platelet aggregation and vasoconstriction. Aspirin and other NSAIDs inhibit the synthesis of thromboxanes by inhibiting the COX enzyme.

Leukotrienes Leukotrienes are also synthesized from arachidonic acid. They occur mainly in leukocytes. They produce muscle contractions, especially in the lungs and thereby can cause asthma-like attacks. In this regard, they are 100 times more potent than histamine. Several recently-developed anti-asthma drugs inhibit the synthesis of leukotrienes.

Chapter 21 Lipids End Chapter 21