Chapter 27. Biomolecules: Lipids

1. Chapter 27. Biomolecules: Lipids Based on McMurry’s Organic Chemistry, 6th edition

2. About Lipids • Naturally 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. 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

4. Fats and Oils • Animal fats and vegetable are triacylglycerols oil • Triesters of glycerol with three long-chain carboxylic acids • Saponification of a fat or oil with (reaction with aqueous NaOH) yields glycerol and three fatty acids

5. Fatty Acids (from Fats and Oils) • Straight-chain (C12 - C20) carboxylic acids • Double bonds are cis-substituted but trans-fatty acid 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)

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

7. 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

8. 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

9. 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 .

10. 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”

11. 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

12. 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

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. 27.4 Prostaglandins • 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

15. Prostaglandin Sources • Biosynthesized from arachidonic acid (C20 unsaturated fatty acid) • Catalyzed by cyclooxygenase (COX)

16. 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)

17. Terpenoids Are Isoprenoids • Terpenoid structures are derived from isoprene (2-methyl-1,3-butadiene) units connected head-to-tail (Isoprene Rule) • The term “head-to-tail” means that dissimilar ends are connected (you can choose which is a “head” and which is a “tail”)

18. Classification of Terpenoids • Classified according to the number of di-isoprenoid (C10) units they contain • Monoterpenes have 10-carbons, sesquiterpenes (sesqui = 1 1/2) have 15-carbons from three isoprene units, and so on

19. Some Important Terpenoids • The triterpene lanosterol is the precursor of steroid hormones • The tetraterpene b-carotene is a source of vitamin A

20. 27.6 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.

21. 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

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

23. Reduction Forms Mevalonate • HMG CoA is reduced to mevalonate • Catalyzed by HMG CoA reductase utilizing NADPH

24. Conversion of Mevalonate to IPP • Pyrophosphorylation gives mevalonyl-PP • Addition of phosphate from ATP followed by loss of CO2 and phosphate

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

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

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

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

29. 27.7 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

30. 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

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

32. 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

33. 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

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

35. 27.8 Stereochemistry of Steroids • Two cyclohexane rings can be joined in either a cis or a trans manner • In cis-decalin, both groups at the ring-junction positions are on the same side of the two rings • In trans-decalin, the groups at the ring junctions are on opposite sides

36. A/B Junction in Steroids • Steroids can have either a cis or a trans fusion of the A and B ring • (B–C and C–D) are usually trans

37. 27.9 Steroid Biosynthesis • Enzyme-catalyzed addition of oxygen atom to squalene • Stereospecific formation of an oxirane from an alkene

38. Cyclization to Steroid • Stork-Eschenmoser mechanism • Enzyme-catalyzed • See Figure 27.6