1. Lipids Chapter 29

2. 2 Lipids are biomolecules that are soluble in organic solvents. The identity of lipids is defined on the basis of a physical property and not by the presence of a particular functional group. Lipids share many properties with hydrocarbons. Figure 29.1 Three examples of lipids Lipids

3. 3 Lipids can be categorized as hydrolyzable and nonhydrolyzable. [2] Nonhydrolyzable lipids cannot be cleaved into smaller units by aqueous hydrolysis. [1] Hydrolyzable lipids can be cleaved into smaller molecules by hydrolysis with water. Many hydrolyzable lipids contain an ester unit. Hydrolyzability of Lipids

4. Waxes Esters of High Mw alcohol and High Mw acid Crystalline pure, plastic and malleable as mixtures Spermacetti (whale oil) – buoyancy mechanism for diving (mix freezes at 30 °C) Bees Wax (mp 60-64 °C), Carnauba (Brazil or palm) wax Cerotic acid C26 carboxylic acid Mostly found as mixtures Also jojoba wax (C36-C46 acids & alcohols) Sebum (includes 20-30% waxes)

5. Essential Fatty acids (no biosynthesis in humans)

6. Triglycerides (oils and fats) Fats melt above room temperature Oils melt below room temperature Unsaturated is always (Z) or (cis) Unsaturated have lower melting points than saturated (butter is a solid, olive oil is a liquid) More unsaturation the lower the melting point.

7. Triglycerides: Cocoa butter Mixture of triglycerides Melts 34 °C (in your mouth) Oleic, palmitic, steric esters

8. Fish oils (cod liver and herring oils) unsaturated to remain liquid in cold water

9. Hydrolysis of Triglycerides Mechanism for hydrolyses?

10. Reactions of unsaturated fatty esters Hydrolysis, transesterification Reduction of C=C Allylic Oxidations

11. Phospholipids (hydrolyzable) phosphoacylglycerols sphingomyelins phosphatidylethanolamine or cephalin phosphatidylcholine or lecithin derivatives of the amino alcohol sphingosine myelin sheath around nerves is rich in sphingomyelins

12. 3D Structure of Phosphoacylglycerols

13. Fat soluble Vitamins: A & D organic compounds required in small quantities for normal metabolism. Not synthesized by organism. Must come from diet. intestinal absorption of calcium and phosphate Deficiency: Rickets Deficiency: Night blindness

14. Fat soluble Vitamins: E & K Blood clotting Deficiency: excessive bleeding Deficiency: neurological problems Antioxidant

15. Eicosanoids group of potent biologically active compounds containing 20 carbon atoms derived from arachidonic acid. prostaglandins, leukotrienes, thromboxanes, and prostacyclins Autocrine or paracrine hormones Lower blood pressure Inhibit platelet aggregation Control inflammation Lower gastric secretions Induce labor Control cell growth Control calcium transport Sensitizes spinal neurons to pain Constrict blood vessels Trigger platelet aggregation Dilate blood vessels Inhibit platelet aggregation Constrict smooth muscle (lungs)

16. 16 Prostaglandins themselves are unstable in the body, having a half-life of only minutes. Thus, more stable analogues have been developed that retain their biological activity for longer periods. An example is misoprostol, an analogue of PGE 1, which is sold as a mixture of stereoisomers. Misoprostol is administered to prevent gastric ulcers in patients who are at high risk of developing them. Prostaglandin Analogs

17. 17 Figure 29.7 The conversion of arachidonic acid to prostaglandins, thromboxanes, prostacyclins, and leukotrienes Synthesis of Eicosanoids Aspirin and other non- steroidal anti- inflammatory drugs (NSAID) inactivate COX 1 & 2 enzymes results in an increase in gastric secretions

18. 18 A group of anti-inflammatory drugs that block only the COX-2 enzyme were developed in the 1990’s. These drugs—rofecoxib, valdecoxib, and celecoxib—do not cause an increase in gastric secretions, and were thus believed to be especially effective for long-term use in patients with arthritis. Unfortunately, both rofecoxib and valdecoxib have been removed from the market, since their use has been associated with increased risk of heart attack and stroke. COX-2 Inhibitors

19. 19 Terpenes are lipids composed of repeating five-carbon units called isoprene units. An isoprene unit has five carbons: four in a row, with a one-carbon branch on a middle carbon. Terpenes can be cyclic or acyclic, and may contain heteroatoms. Terpenes

20. Indentifying terpenes Squalene in sebaceous oils

22. Terpene biosynthesis (carbocation chemistry)

23. Terpene biosynthesis

24. 24 All other terpenes are formed from farnesyl and geranyl diphosphates

25. Formation of cyclic terpenes

26. Steroids Cholesterol 8 chiral centers 2 8 =256 possible stereoisomers biosynthesis in the body from squalene (C 30 ). Hormones Surfactants (membranes) Oils

27. Biosynthesis of Cholesterol

28. More stable

29. 29 Several drugs are now available to reduce the level of cholesterol in the bloodstream. These compounds act by blocking the biosynthesis of cholesterol in its early stages. Two examples are atorvastatin (Lipitor) and simvastatin (Zocor). Figure 29.12 Cholesterol-Lowering Drugs

30. 30 Steroidal Sex Hormones

31. 31 Synthetic analogues of these steroids have found important uses, such as in oral contraceptives. Synthetic androgen analogues, called anabolic steroids, promote muscle growth. Although they are used by athletes, their use is not permitted in competitive sports. Synthetic Hormone Steroids

32. 32 A second group of steroid hormones includes the adrenal cortical steroids. Examples are cortisone, cortisol, and aldosterone. All of these compounds are synthesized in the outer layer of the adrenal gland. Cortisone and cortisol serve as anti-inflammatory agents and they also regulate carbohydrate metabolism. Aldosterone regulates blood pressure and volume by controlling the concentration of Na + and K + in body fluids. Adrenal Cortical Steroids

33. Lanolin “lana” wool “Olin” from oleum for oil 5-25 wt% of wool is lanolin oil 40% alpha hydroxyesters No triglycerides Waxes Cholesterol esters Sebaceous glands R = C 10 -C 22