John E. McMurry Paul D. Adams University of Arkansas Chapter 27 Biomolecules: 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 About Lipids

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

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

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

 Straight-chain (C 12 - C 20 ) 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 (C 16 ) and stearic (C 18 ) Fatty Acids (from Fats and Oils)

 Oleic (C 18 with one C=C) and linolenic (C 18 with 3 C=C) are the most abundant unsaturated Unsaturated and Polyunsaturated Fatty Acids

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

 “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. Detergents

 Phospholipids are diesters of H 3 PO 4, phosphoric acid  Phosphoric acid can form monoesters, diesters and triesters  In general these are known as “phosphates” 27.3 Phospholipids

 Contain a glycerol backbone linked by ester bonds to two fatty acids and phosphoric acid  Fatty acid residues with C 12 –C 20  The phosphate group at C3 has an ester link to an amino alcohol Phosphoglycerides

 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. Sphingolipids

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

 C 20 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 27.4 Prostaglandins and Other Eicosanoids

 Biosynthesized from arachidonic acid (C 20 unsaturated fatty acid) Prostaglandin Sources

 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) 27.5 Terpenoids

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

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

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

 HMG CoA is reduced to mevalonate  Catalyzed by HMG CoA reductase utilizing NADPH Reduction

 Pyrophosphorylation gives mevalonyl-PP  Addition of phosphate from ATP followed by loss of CO 2 and phosphate Phosphorylation and Decarboxylation

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

 Isomerization of IPP to DMAPP is catalyzed by IPP isomerase through a carbocation pathway Mechanism of Isomerization

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

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

 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 27.6 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 Functions of Steroids

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

 Estrone and estradiol are the two most important female sex hormones, or estrogens  Progesterone is the most important progestin, steroids that function during pregnancy Female Sex 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 Adrenocortical Hormones

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

 Enzyme-catalyzed addition of oxygen atom to squalene  Stereospecific formation of an oxirane from an alkene 27.7 Biosynthesis of Steroids

Let’s Work a Problem The plasmologens are a group of lipids found in nerve and muscle cells. How do plasmalogens differ from fats?

Answer This problem asks you to recall the different lipid structural features. The plasmologens differ from the fats in that, in plasmalogens, the C3 is a vinyl ether as opposed to a fat, which has a carboxylic acid ester at the corresponding position