Chapter 27.

Biomolecules: Lipids

Based on McMurrys Organic Chemistry, 6th

edition
2003 Ronald Kluger
Department of Chemistry
University of Toronto
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
cant be hydrolyzed

Based on McMurry, Organic Chemistry, Chapter 2

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 3

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 4

27, 6th edition, (c) 2003
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)

Based on McMurry, Organic Chemistry, Chapter 5

27, 6th edition, (c) 2003
Unsaturated and Polyunsaturated Fatty
Acids
Oleic (C18 with one C=C) and linolenic (C18 with 3
C=C) are the most abundant unsaturated

Based on McMurry, Organic Chemistry, Chapter 6

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 7

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 8

27, 6th edition, (c) 2003
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 .

Based on McMurry, Organic Chemistry, Chapter 9

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 10

27, 6th edition, (c) 2003
Phosphoglycerides
Contain a glycerol backbone linked by ester bonds to
two fatty acids and phosphoric acid
Fatty acid residues with C12C20
The phosphate group at C3 has an ester link to an
amino alcohol

Based on McMurry, Organic Chemistry, Chapter 11

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 12

27, 6th edition, (c) 2003
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.

Based on McMurry, Organic Chemistry, Chapter 13

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 14

27, 6th edition, (c) 2003
Prostaglandin Sources
Biosynthesized from arachidonic acid (C20
unsaturated fatty acid)
Catalyzed by cyclooxygenase (COX)

Based on McMurry, Organic Chemistry, Chapter 15

27, 6th edition, (c) 2003
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)

Based on McMurry, Organic Chemistry, Chapter 16

27, 6th edition, (c) 2003
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)

Based on McMurry, Organic Chemistry, Chapter 17

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 18

27, 6th edition, (c) 2003
Some Important Terpenoids
The triterpene lanosterol is the precursor of
steroid hormones
The tetraterpene -carotene is a source of
vitamin A

Based on McMurry, Organic Chemistry, Chapter 19

27, 6th edition, (c) 2003
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.

Based on McMurry, Organic Chemistry, Chapter 20

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 21

27, 6th edition, (c) 2003
Aldol Condensation Produces
HMG-CoA
Carbonyl condensation reaction of acetoacetyl CoA with acetyl
CoA
Produces 3-hydroxy-3-methylglutaryl CoA (HMG-CoA)

Based on McMurry, Organic Chemistry, Chapter 22

27, 6th edition, (c) 2003
Reduction Forms Mevalonate
HMG CoA is reduced to mevalonate
Catalyzed by HMG CoA reductase utilizing NADPH

Based on McMurry, Organic Chemistry, Chapter 23

27, 6th edition, (c) 2003
Conversion of Mevalonate to IPP
Pyrophosphorylation gives mevalonyl-PP
Addition of phosphate from ATP followed by loss of
CO2 and phosphate

Based on McMurry, Organic Chemistry, Chapter 24

27, 6th edition, (c) 2003
Conversion of Isopentenyl
Diphosphate to Terpenoids
For triterpenes and larger, head-to-head coupling of
farnesyl diphosphates gives squalene

Based on McMurry, Organic Chemistry, Chapter 25

27, 6th edition, (c) 2003
Mechanism of Isomerization
Isomerization of IPP to DMAPP is catalyzed by IPP
isomerase through a carbocation pathway

Based on McMurry, Organic Chemistry, Chapter 26

27, 6th edition, (c) 2003
Coupling Mechanism
Nucleophilic substitution reaction in which the double
bond of IPP behaves as a nucleophile in displacing
diphosphate ion leaving group (PPO)

Based on McMurry, Organic Chemistry, Chapter 27

27, 6th edition, (c) 2003
Conversions of Monoterpenoids
Typically involves carbocation intermediates and
multistep reaction pathways catalyzed by a terpene
cyclase

Based on McMurry, Organic Chemistry, Chapter 28

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 29

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 30

27, 6th edition, (c) 2003
Male Sex Hormones
Testosterone and androsterone are the two most
important male sex hormones, or androgens
Androstanedione is a precursor

Based on McMurry, Organic Chemistry, Chapter 31

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 32

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 33

27, 6th edition, (c) 2003
Synthetic Steroids
Made in pharmaceutical laboratories as new drugs
Includes oral contraceptives and anabolic agents
Methandrostenolone is an anabolic steroid used for
tissue-building

Based on McMurry, Organic Chemistry, Chapter 34

27, 6th edition, (c) 2003
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

Based on McMurry, Organic Chemistry, Chapter 35

27, 6th edition, (c) 2003
A/B Junction in Steroids
Steroids can have either a cis or a trans fusion of the
A and B ring
(BC and CD) are usually trans

Based on McMurry, Organic Chemistry, Chapter 36

27, 6th edition, (c) 2003
27.9 Steroid Biosynthesis
Enzyme-catalyzed addition of oxygen atom to
squalene
Stereospecific formation of an oxirane from an alkene

R
R

O2

Enzyme

Squalene 2,3-Oxidosqualene

Based on McMurry, Organic Chemistry, Chapter 37

27, 6th edition, (c) 2003
Cyclization to Steroid
Stork-Eschenmoser mechanism
Enzyme-catalyzed
See Figure 27.6

R R

O HO protosteryl cation
E-H

Based on McMurry, Organic Chemistry, Chapter 38

27, 6th edition, (c) 2003