The Chemistry of Lipids PDF

THE CHEMISTRY OF LIPIDS Complex and Derived Lipids  COMPLEX LIPIDS Schematic diagram of simple and complex lipids. 2  BIOLOGICAL MEMBRANES Complex lipids form the membranes around cells and around sm...

THE CHEMISTRY OF LIPIDS Complex and Derived Lipids  COMPLEX LIPIDS Schematic diagram of simple and complex lipids. 2  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 force for 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). 3 FLUID MOSAIC MODEL 4  PHOSPHOLIPIDS ▪ Phospholipids are similar in structure to triacylglycerol but replace one fatty acid group with a phosphate group and an amino alcohol. ▪ It contain an alcohol, two fatty acids, and a phosphate ester. ▪ can be degraded to their component parts by a family of enzymes called phospholipases  GLYCEROPHOSPHOLIPIDS Glycerophospholipids, also called phosphoglycerides are the second most abundant group of naturally occurring lipids, and are membrane components of cells throughout the bodyThe 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. 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 fatty acid on carbon 2 of glycerol is always unsaturated. Further esterification with a low-molecular-weight alcohol (screen 16) gives a glycerophospholipid. 6  GLYCEROPHOSPHOLIPIDS LECITHIN is a glycerophospholipid in which the addition phosphate ester is attached with Choline. It a major component of egg yolk. It has both polar and nonpolar portions within one molecule, and an excellent Emulsifier. 7  GLYCEROPHOSPHOLIPIDS CEPHALINS: Another group of glycerophospholipids in which the additional phosphate ester is provided by either ethanolamine or serine. 8  GLYCEROPHOSPHOLIPIDS PHOSPHATIDYLINOSITOLS (PI) - the alcohol inositol is bonded to the rest of the molecule by a phosphate ester bond. The higher phosphorylated Form of PI , phosphatidylinositol 4,5-bisphosphates (PIP2), serve as signaling molecules in chemical communication  SPHINGOLIPIDS Contain the long-chain amino alcohol, sphingosine, from which this class of compounds in named. The sphingolipid myelin is found in the coatings of nerve axons. The ceramide part of complex lipids may contain different fatty acids. E.g. Stearic acid occurs mainly in sphingomyelin They can be found in cerebrosides 10  GLYCOLIPIDS Glycolipid: a complex lipid that contains carbohydrates and ceramides. The carbohydrate is either glucose or galactose. The cerebrosides consists of ceramide mono- or oligosaccharides, and occur primarily in the brain and at the nerve synapse. Gangliosides contain more complex carbohydrates 11  DERIVED LIPIDS STEROIDS ▪ A compound that contains the steroid nucleus - a tetracyclic ring structure consisting of three cyclohexane rings and one cyclopentane ring fused together (no fatty acids). The different functionality of steroids comes from the substituent groups attached to the core structure. ▪ The four rings in the steroid nucleus are designated A, B, C, and D. The carbon atoms are numbered beginning with the carbons in ring A and, in types of steroids like cholesterol, ending with two methyl groups (attached groups make a wide variety of steroid compounds).  CHOLESTEROL 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. 13  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. 14 LOW-DENSITY LIPOPROTEIN 15  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. 16  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. 17  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 rise as high as 680 mg/100 mL. 18  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. 19  STEROID HORMONES Cholesterol is the starting material for the synthesis of steroid hormones. It is first converted to progesterone and then to both sex hormones and adrenocorticoid hormones. 20  STEROID HORMONES Male sex hormones Synthesized in the testes from cholesterol. Responsible for the development of male secondary sex characteristics. 21  STEROID HORMONES Among the synthetic anabolic steroids are: 22  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. 23  STEROID HORMONES Progesterone-like analogs are used in oral contraceptives: 24  GLUCOCORTICOID HORMONES Glucocorticoid hormones Synthesized in the adrenal cortex. Regulate metabolism of carbohydrates. Decrease inflammation. Involved in the reaction to stress. 25  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. 26  PROSTAGLANDINS Prostaglandins: a family of compounds that have the 20-carbon skeleton of prostanoic acid. 27  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. 28  PROSTAGLANDINS 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. 29  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. 30  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. They are 100x more potent than histamine. Several recently-developed anti-asthma drugs inhibit the synthesis of leukotrienes. 31