Chapter 27. Biomolecules: Lipids

Based on McMurry’s Organic Chemistry, 6th edition

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

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

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

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)

Unsaturated and Polyunsaturated Fatty Acids

• Oleic (C18 with one C=C) and linolenic (C18 with 3 C=C) are the most abundant unsaturated

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

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

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 .

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”

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

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

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.

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

Prostaglandin Sources

• Biosynthesized from arachidonic acid (C20 unsaturated fatty acid)

• Catalyzed by cyclooxygenase (COX)

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)

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”)

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

Some Important Terpenoids

• The triterpene lanosterol is the precursor of steroid hormones

• The tetraterpene -carotene is a source of vitamin A

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.

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

Aldol Condensation Produces HMG-CoA

• Carbonyl condensation reaction of acetoacetyl CoA with acetyl CoA

• Produces 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)

Reduction Forms Mevalonate

• HMG CoA is reduced to mevalonate

• Catalyzed by HMG CoA reductase utilizing NADPH

Conversion of Mevalonate to IPP

• Pyrophosphorylation gives mevalonyl-PP

• Addition of phosphate from ATP followed by loss of CO2 and phosphate

Conversion of Isopentenyl Diphosphate to Terpenoids

• For triterpenes and larger, head-to-head coupling of farnesyl diphosphates gives squalene

Mechanism of Isomerization

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

Coupling Mechanism

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

Conversions of Monoterpenoids

• Typically involves carbocation intermediates and multistep reaction pathways catalyzed by a terpene cyclase

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

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

Male Sex Hormones

• Testosterone and androsterone are the two most important male sex hormones, or androgens

• Androstanedione is a precursor

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

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

Synthetic Steroids

• Made in pharmaceutical laboratories as new drugs

• Includes oral contraceptives and anabolic agents

• Methandrostenolone is an anabolic steroid used for tissue-building

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

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

27.9 Steroid Biosynthesis

• Enzyme-catalyzed addition of oxygen atom to squalene

• Stereospecific formation of an oxirane from an alkene

R

O

R

Squalene 2,3-Oxidosqualene

Enzyme

O2

Cyclization to Steroid

• Stork-Eschenmoser mechanism

• Enzyme-catalyzed

• See Figure 27.6

R

OE-H

R

HO protosteryl cation