Lipids

1. Lipids Chapter 29

2. Lipids • 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

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

4. Waxes Mostly found as mixtures • 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 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 Oleic, palmitic, steric esters Mixture of triglycerides Melts 34 °C (in your mouth)

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 myelin sheath around nerves is rich in sphingomyelins derivatives of the amino alcohol sphingosine

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. Deficiency: Night blindness intestinal absorption of calcium and phosphate Deficiency: Rickets

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

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 smooth muscle (lungs) Dilate blood vessels Inhibit platelet aggregation Constrict blood vessels Trigger platelet aggregation

16. Prostaglandin Analogs • 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 PGE1, 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.

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

18. COX-2 Inhibitors • 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.

19. Terpenes • 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.

20. Indentifying terpenes Squalene in sebaceous oils

22. Terpene biosynthesis (carbocation chemistry)

23. Terpene biosynthesis

24. All other terpenes are formed from farnesyl and geranyldiphosphates

25. Formation of cyclic terpenes

26. Steroids Hormones Surfactants (membranes) Oils Cholesterol 8 chiral centers 28 =256 possible stereoisomers biosynthesis in the body from squalene (C30).

27. Biosynthesis of Cholesterol

28. More stable

29. Cholesterol-Lowering Drugs • 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

30. Steroidal Sex Hormones

31. Synthetic Hormone Steroids • 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.

32. Adrenal Cortical Steroids • 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.

33. Lanolin “lana” wool “Olin” from oleumfor oil 5-25 wt% of wool is lanolin oil 40% alpha hydroxyesters No triglycerides Waxes Cholesterol esters Sebaceous glands R = C10-C22