Chapter 27. Biomolecules: Lipids

1. Chapter 27. Biomolecules: Lipids Based on McMurry’s Organic Chemistry, 7th edition

2. About Lipids • Natural materials that preferentially extract into nonpolar organic solvents • Includes fats, oils, waxes, some vitamins and hormones, some components of membrane • General types: esters (“saponifiable”) and those that can’t be hydrolyzed

3. Why this Chapter? • Lipids are the largest and most diverse class of biomolecules • To examine lipid structure, function, and metabolism

4. 27.1 Waxes, Fats, and Oils • Waxes - contain esters formed from long-chain (C16-C36) carboxylic acids and long-chain alcohols (C24-C36) • Triacontyl hexadecanoate is in beeswax

5. Triacylglycerol • Tri-esters of glycerol with three long-chain carboxylic acids, fatty acids.

6. Fatty Acids (from Fats and Oils) • Straight-chain (C12 - C20) carboxylic acids • Double bonds are cis-substituted but trans-fatty acids also occur • A fat or oil in nature occurs as a mixture of many different triacylglycerols • The most abundant saturated fatty acids are palmitic (C16) and stearic (C18)

7. Unsaturated and Polyunsaturated Fatty Acids • Oleic (C18 with one C=C) and linolenic (C18 with 3 C=C) are the most abundant unsaturated

8. 27.2 Soap • A mixture of sodium or potassium salts of long-chain fatty acids produced by alkaline hydrolysis (saponification) of animal fat with alkali

9. Cleansing Action of Soap • The carboxylate end of the long-chain molecule is ionic and therefore is preferentially dissolved in water • The hydrocarbon tail is nonpolar and dissolves in grease and oil • Soaps enable grease to be dissolved into water

10. Detergents • “Hard” water contains Mg+2 and Ca+2 that form insoluble salts with soaps • Synthetic detergents are alkylbenzene sulfonates that dissolve dirt like soaps but do not form scums with Mg+2 and Ca+2 .

11. 27.3 Phospholipids • Phospholipids are diesters of H3PO4, phosphoric acid • Phosphoric acid can form monoesters, diesters and triesters • In general these are known as “phosphates”

12. Phosphoglycerides • Contain a glycerol backbone linked by ester bonds to two fatty acids and phosphoric acid • Fatty acid residues with C12–C20 • The phosphate group at C3 has an ester link to an amino alcohol

13. Sphingolipids • The other major group of phospholipids • Sphingosine or a dihydroxyamine backbone • Constituents of plant and animal cell membranes • Abundant in brain and nerve tissue, as coating around nerve fibers.

14. Phosphoglyceride Membranes • Phosphoglycerides comprise the major lipid component of cell membranes • Nonpolar tails aggregate in the center of a bilayer • Ionic head is exposed to solvent

15. 27.4 Prostaglandins and Other Eicosanoids • C20 lipids that contain a five-membered ring with two long side chains • Present in small amounts in all body tissues and fluids • Many physiological effects

16. Prostaglandin Sources • Biosynthesized from arachidonic acid (C20 unsaturated fatty acid)

17. 27.5 Terpenoids • Steam distillation of plant extracts produces “essential oils” • Chemically related to compounds in turpentine (from pine sap) called terpenes and thus called terpenoids • Mostly hydrocarbons (some oxygens) that do not contain esters (stable to hydrolysis)

18. Biosynthesis of Terpenoids • Isopentenyl pyrophosphate (IPP) forms higher isoprenoids in reactions catalyzed by prenyl transferase • Monoterpenoids, diterpenoids, and tetraterpoids arise from 1-deoxyxylulose 5-phosphate (DXP).

19. Mevalonate Pathway to Isopentenyl Diphosphate • Begins with the conversion of acetate to acetyl CoA followed by Claisen condensation to yield acetoacetyl CoA • Catalyzed by acetoacetyl-CoA acetyltransferase

20. Aldol Condensation • Carbonyl condensation reaction of acetoacetyl CoA with acetyl CoA • Produces 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)

21. Reduction • HMG CoA is reduced to mevalonate • Catalyzed by HMG CoA reductase utilizing NADPH

22. Phosphorylation and Decarboxylation • Pyrophosphorylation gives mevalonyl-PP • Addition of phosphate from ATP followed by loss of CO2 and phosphate

23. Conversion of Isopentenyl Diphosphate to Terpenoids • For triterpenes and larger, head-to-head coupling of farnesyl diphosphates gives squalene

24. Mechanism of Isomerization • Isomerization of IPP to DMAPP is catalyzed by IPP isomerase through a carbocation pathway

25. Coupling Mechanism • Nucleophilic substitution reaction in which the double bond of IPP behaves as a nucleophile in displacing diphosphate ion leaving group (PPO)

26. Conversions of Monoterpenoids • Typically involves carbocation intermediates and multistep reaction pathways catalyzed by a terpene cyclase

27. 27.6 Steroids • Steroids,are another class of nonsaponifiable lipid, defined by structure • Has four fused rings A, B, C, and D, beginning at the lower left • Carbon atoms are numbered beginning in the A ring • The six-membered rings are in fixed chair conformations

28. Functions of Steroids • In humans as hormones, steroids are chemical messengers secreted by glands and carried through the bloodstream to target tissues • Also widely distributed as cholesterol

29. Male Sex Hormones • Testosterone and androsterone are the two most important male sex hormones, or androgens • Androstanedione is a precursor

30. Female Sex Hormones • Estrone and estradiol are the two most important female sex hormones, or estrogens • Progesterone is the most important progestin, steroids that function in pregnancy

31. Adrenocortical Hormones • Adrenocortical steroids: secreted by the adrenal glands near the upper end of each kidney • Mineralocorticoids: control tissue swelling by regulating cellular salt balance • Glucocorticoids: regulation of glucose metabolism and in the control of inflammation

32. Synthetic Steroids • Made in pharmaceutical laboratories as new drugs • Includes oral contraceptives and anabolic agents • Methandrostenolone is an anabolic steroid used for tissue-building

33. 27.7 Steroid Biosynthesis • Enzyme-catalyzed addition of oxygen atom to squalene • Stereospecific formation of an oxirane from an alkene