Unit 5.

Chemistry of naturally occurring Bio-organic compounds

5.1. Carbohydrates
➢ Introduction:
➢ Carbohydrate was defined as hydrates of carbon [C(H2O)]n based on empirical
formula
➢ Carbohydrates are in fact is polyhydroxy ketone or aldehyde rather than carbon
hydrate
➢ Nomenclature and Structure
➢ Monosaccharides (simple sugars) are non hydrolysable molecules
➢ Disaccharide contains two monosaccharide linked by glycosidic bonds
➢ Oligo saccharides contain- usually 2 to 10 monosaccharide
➢ Polysaccharides are polymers of the simple sugars
➢ A comprehensive nomenclature is needed to obtain precision in a classification
scheme, distinguishing one sugar from another when only subtle differences
exist between the two

259
➢ Organic chemistry gives us terms such as D and L isomers, chiral centers,
enantiomers, diastereoisomers, etc. to identify d/t sugar molecules
➢ Anomeric carbon, in cyclic sugars is used to identify alpha and beta sugars
➢ “OSE” is the suffix denoting a aldo sugar and “ULOSE” denotes a keto sugar
➢ The monosaccharides you will encounter in biochemistry have 3, 4, 5, 6, and
7 carbons
➢ Prefixes such as tri, tetra, penta, hexa, and hepta are used to indicate the
number of carbons in monosaccharides
➢ Example:
➢ The term aldopentose denotes two structural features, chain length and
functional group
➢ The chemical structures of carbohydrates are commonly represented by
wedge-and-dash structures or by Fischer projections
➢ Fischer projections are used though out this discussion

260
 Common natural Monosaccharides
➢ A monosaccharide can be a polyhydroxy aldehyde such as D-glucose or a
polyhydroxy ketone such as D-fructose
➢ Monosaccharides are also classified according to the number of carbons they
contain:
➢ Monosaccharides with three carbons are trioses, those with four carbons are
tetroses, those with five carbons are pentoses, and those with six and seven
carbons are hexoses and heptoses, respectively
➢ Trioses: Glyceraldehyde is the simplest aldo-three carbon sugar, with two
isomers:
➢ D-Glyceraldehyde is (R) (+)-glyceraldehyde, and (L) glyceraldehyde is (S)-(-)-
glyceraldehyde

HC O HC O

H OH HO H

CH2OH CH2OH

D-Glyceraldehyde L-Glyceraldehyde

261
➢ The notations D and L are used to describe the configurations of carbohydrates and amino
acids
➢ so it is important to learn what D and L signify
➢ In Fischer projections of monosaccharides, the carbonyl group is always placed on top (in the
case of aldoses) or as close to the top as possible (in the case of ketoses)
➢ If the OH group attached to the bottom-most asymmetric carbon (the carbon that is second
from the bottom) is on the right, then the compound is a D-sugar
➢ If the OH group is on the left, then the compound is an L-sugar
➢ Almost all sugars found in nature are D-sugars and mirror image of a D-sugar is an L-sugar
➢ Like R and S, D and L indicate the configuration of an asymmetric carbon, but they do not
indicate whether the compound rotates polarized light to the right (+) or to the left (-)
➢ For example, D-glyceraldehyde is dextrorotatory, whereas D-lactic acid is levorotatory
HC O COOH

H OH H OH

CH2OH CH2OH

D-(+)-Glyceraldehyde D-(-)-lactic acid

262
➢ Monosaccharides have two or more chiral centers, and stereoisomer of
given chain monosaccharide with ‘n’ chiral center is given by 𝟐𝐧
➢ Tetrose
➢ Aldotetroseshave two asymmetric carbons and therefore (22 =4 )four
stereoisomers
➢ Two of the stereoisomers are D-sugars and two are L-sugars
➢ The names of the aldotetroses—erythroseand threose is used two a pair
of enantiomers

HC O HC O
HC O HC O
H OH
HO H
HO H H OH
H OH
H OH HO H HO H
CH2OH
CH2OH CH2OH CH2OH
D-Erythrose
D-Threose L-Erythrose L-Threose

263
➢ Pentose and hexose
➢ Aldopentoses have three asymmetric carbons and therefore (23 =8) eight
stereoisomers
➢ (four pairs of enantiomers), while aldohexoses have four asymmetric
carbons and 24 =16 stereoisomers (eight pairs of enantiomers)
➢ The four D-aldopentoses and the eight D-aldohexoses
➢ Diastereomers that differ in configuration at only one asymmetric carbon
are called epimers
➢ For example, D-ribose and D-arabinose are C-2 epimers (they differ in
configuration only at C-2), and D-idose and D-talose are C-3 epimers
As xylose cannot be
HC O broken down in
H H humans, it does not
H OH increase blood sugar
H OH levels, so is used in
CH2OH sugar-free foods for
deoxyribose D-lyxose people with diabetes
or a need to control
C-3 epimer
their weight
264
➢ Two very important D-ketopentoses are D-xyulose is 3-epimer of of ribulose

CH2OH
C O In all natural occurring keto sugars, the
H OH carbonyl carbon is found on the second
H OH carbon
CH2OH

D-Ribulose

OH

265
5.1.1 Glucose
➢ Aldohexose include 16 (8D + 8L) stereoisomer,
➢ Glucose is one D-aldohexose which is the main constituents of blood sugar
➢ Glucose is also the monomer in starch and cellulose
➢ the D series are drawn below and your expected to draw all the L series:

266
➢ D-Glucose, D-mannose, and D-galactose are the most common aldohexoses
in biological systems, notice that D-mannose is the C-2 epimer of D-glucose
and D-galactose is the C-4 epimer of D-glucose
➢ Naturally occurring ketoses have the ketone group in the 2-position
➢ The configurations of the D-2-ketoses which are encountering nature:

267
➢ Chemical reaction of monosaccharides:
➢ Redox Reactions of Monosaccharides:
➢ The common Monosaccharides have two types of functional groups: the
carbonyl and alcohol functional group, therefore, monosaccharides will
undergo the basic reaction of carbonyl on aldehyde or ketone and alcohol
functional group
➢ For example, an aldehyde group in a monosaccharide can be oxidized or
reduced and can react with nucleophiles to form imines, hemiacetals, and
acetals
➢ Reduction
➢ The carbonyl group of aldoses and ketoses can be reduced by the usual
carbonyl-group reducing agents (e.g., LiAlH4 and NaBH4)
➢ The product of the reduction is a polyalcohol, known as an alditol
➢ Reduction of a ketose forms two alditols because the reaction creates a new
asymmetric carbon in the product

268
➢ Oxidation
➢ Aldoses can be distinguished from ketoses by observing what happens to
the color of an aqueous solution of bromine when it is added to the sugar
➢ Br2 is a mild oxidizing agent and easily oxidizes the aldehyde group, but it
cannot oxidize ketones or alcohols
➢ Consequently, if a small amount of an aqueous solution of Br2 is added to
an unknown monosaccharide, the reddish-brown color of it will disappear
if the monosaccharide is an aldose, but will persist if the monosaccharide
is a ketose
➢ The product of the oxidation reaction is an aldonic acid

269
➢ Both aldoses and ketoses are oxidized to aldonic acids by Tollens reagent (Ag+,
NH3, and –OH) so that reagent cannot be used to distinguish between aldoses
and ketoses

270
➢ Osazone Formation
➢ Emil Fischer found that when phenyl hydrazine is added to an aldose or a
ketose, a yellow crystalline solid that is insoluble in water is formed
➢ These derivatives are called an osazone (“ose” for sugar; “azone” for
hydrazone)
➢ Osazones are easily isolated and purified and were once used extensively to
identify monosaccharides

271
5.1.3 Anomeric forms of Monosaccharides
Cyclic Structure of Monosaccharides: Hemiacetal Formation
➢ D-Glucose exists in three different forms: the open-chain form of D-glucose
and two cyclic forms α-D-glucose and β-D-glucose
➢ The two cyclic forms are different, because they have different physical
properties: α-D-Glucose melts at 146 °C, whereas β-D-glucose melts at 150 °C;
α-D-glucose has a specific rotation of 112.2o whereas β-D-glucose has a
specific rotation of +18.7o
➢ Recall that an aldehyde reacts with an equivalent of an alcohol to form a
hemiacetal
➢ A monosaccharide such as D-glucose has an aldehyde group and several
alcohol groups
➢ The alcohol group bonded to C-5 of D-glucose reacts intramolecularly with the
aldehyde group, forming a six-membered-ring hemiacetal
➢ Two different hemiacetals are formed because the carbonyl carbon of the
open-chain sugar becomes a new asymmetric carbon in the hemiacetal
➢ If the OH group bonded to the new asymmetric carbon is on the right on
Fischer projection, the hemiacetal is α-D-glucose; If the OH group is on the
left, the hemiacetal is β-D-glucose 272
 HC OH H Anomeric carbon
HO C
H OH HC O
H OH
HO H H OH
HO H
OH
HO H
H OH
H OH
H OH HO O
≡H O ≡
CH2OH H OH
H O
HO OH
CH2OH
CH2OH OH
α-D-Glucose
β-D-glucose

➢ α-D-Glucose and β-D-glucose are called anomers

➢ Anomers are two sugars that differ in configuration only at the carbon that
was the carbonyl carbon in the open-chain form
➢ This carbon is called the anomeric carbon
➢ Whether a five- or a six-membered ring is formed depends on their relative
stabilities
➢ Six-membered-ring sugars are called pyranoses, and five membered-ring
sugars are called furanoses

273
Ketoses also exist predominantly in cyclic forms
➢ D-Fructose forms a five-membered ring-hemiketal as a consequence of the C-
5 OH group reacting with the ketone carbonyl group
➢ If the new asymmetric carbon has the OH group on the right in a Fischer
projection, the compound is α-D-fructose; if the OH group is on the left, the
compound is β-D-fructose
➢ These sugars can also be called α-D-fructofuranose and β-D-fructofuranose
➢ D-Fructose can also form a six-membered ring by using the C-6 OH group
➢ The pyranose form predominates in the monosaccharide, whereas the
furanose form predominates when the sugar is part of a disaccharide
CH2OH
HOCH2 O O
CH2OH HO H
HO OH H OH O CH2OH
H OH HO OH
HO HO OH
CH2OH
α-D-fructofuranose α-D-fructopyranose

274
 Fischer projections

Haworth projections
α-D-fructofuranose β-D-fructofuranose α-D-fructopyranose β-D-fructopyranose

275
5.1.4 Glycosides
➢ Sugars in the form of acetals are called glycosides, and their names end in the –
”oside” suffix
➢ For example, a glycoside of glucose would be a glucoside, and if it were a six-
membered ring, it would be a glucopyranoside
➢ Similarly, a glycoside of ribose would be a riboside, and if it were a five-
membered ring, it would be a ribofuranoside
➢ Formation of Glycosides
➢ Previously we have seen aldehydes and ketones are converted to acetals by
treatment with an alcohol and a trace of acid catalyst
➢ These conditions also convert aldoses and ketoses to the acetals we call
glycosides
➢ For example, the acid-catalyzed reaction of glucose with methanol gives a
mixture of methyl glucosides

276
➢ Like other acetals, glycosides are stable to basic conditions, but they hydrolyze
in aqueous acid to a free sugar and an alcohol

➢ An aglycone is the group bonded to the anomeric carbon atom of a glycoside

➢ For example, methanol is the aglycone in a methyl glycoside
➢ Many aglycones are bonded through an oxygen atom, but others are bonded
through a nitrogen atom or some other heteroatom
➢ Disaccharides and polysaccharides are glycosides in which the alcohol forming
the glycoside bond is an (-OH) group of another monosaccharide

277
5.1.5 Disaccharides
➢ The acetal (or ketal) of a sugar is called a glycoside, and the bond between
the anomeric carbon and the alkoxy oxygen is called a glycosidic bond
➢ Glycosides are named by replacing the “e” ending of the sugar’s name with
“ide”
➢ If the hemiacetal group of a monosaccharide forms an acetal by reacting with
an additional alcohol group of another monosaccharide, the glycoside that is
formed is a disaccharide
➢ Disaccharides are compounds consisting of two monosaccharide subunits
hooked together by an acetal linkage (glycosidic bond)
➢ For example, maltose is a disaccharide obtained from the hydrolysis of starch
➢ It contains two D-glucose subunits hooked together by an acetyl linkage
➢ This particular acetal linkage is called an α-1,4’-glycosidic linkage

278
 • Maltose is a disaccharide
✓ obtained from the hydrolysis of
starch
✓ It contains two D-glucose
subunits hooked together by an
acetal linkage
✓ This particular acetal linkage is
called an α-1,4’-glycosidic
maltose linkage

✓ Cellobiose, a disaccharide obtained

from the hydrolysis of cellulose,
also contains two D-glucose
subunits
✓ Cellobiose differs from maltose in
that the two glucose subunits are
hooked together by a β-1,4’-
cellobiose glycosidic linkage

279
 α-glucopyranoside β-fructofrunoside
OH HOCH
6 1 2
HO 4 5 O O
1 2 H
HO 3 2 HO 5 Sucrose
OH O 3
4 CH OH
HO 6 2
lactose An α-1,2-glycoside

➢ Lactose is a ➢ In sucrose the two anomeric “OH” is

disaccharide found in condensed
➢ Sucrose is not a reducing sugar because the
milk glycosidic bond is between the anomeric
➢ Lactose constitutes carbon of glucose and the anomeric carbon of
4.5% of cow’s milk by fructose
weight and 6.5% of ➢ Sucrose has a specific rotation of 66.5o
human milk ➢ An equimolar mixture of glucose and fructose
has a specific rotation of -22.0o
➢ The enzyme that catalyzes the hydrolysis of
sucrose is called invertase [α] since change sign
from + → -
280
➢ Reducing and Nonreducing Sugars
➢ Hemiacetals (or hemiketals) are in equilibrium with the open-chain sugars in
aqueous solution
➢ So as long as a sugar has an aldehyde, α-hydroxy ketone, as in a hemiacetal, or
a hemiketal group, it is able to reduce an oxidizing agent and therefore is
classified as a reducing sugar
➢ In order to be a reducing sugar, the molecule must contain a free anomeric
carbon, since it is the open-chain form of the aldehyde that is able to react (and
be oxidized)
➢ Without one of these groups, it is a non-reducing sugar
➢ Since glycosides are acetals (or ketals), they are not in equilibrium with the open
chain aldehyde (or ketone) in neutral or basic aqueous solutions and cannot be
oxidized by reagents such as Ag+ or Cu2+
➢ Glycosides, therefore, are non-reducing sugars—they cannot reduce Ag+ , Cu2+
or Br2

281
5.1.6 Polysaccharides
➢ Polysaccharides contain as few as 10 or as many as several thousand
monosaccharide units joined together by glycosidic linkages
➢ The molecular weight of the individual polysaccharide chains is variable
➢ The most common polysaccharides are starch and cellulose
➢ Starch is the major component of flour, potatoes, rice, beans, corn, and peas
➢ Starch is a mixture of two different polysaccharides: amylose (about 20%) and
amylopectin (about 80%)
➢ Amylose is composed of unbranched chains of D-glucose units joined by
α-1,4’ glycosidic linkages
➢ Amylopectin is a branched polysaccharide
➢ Like amylose, it is composed of chains of D-glucose units joined by α-1,4’-
glycosidic linkages and at branches by α -1,6’ glycosidic linkages

Amylose, an α-(1-4)-D-Glucopyranoside polymer

282
283
 ➢ The glucose units in cellulose are joined by β-1,4’-glycosidic linkages rather
than by α-1,4-glycosidic linkages, structurally, β-linkages in cellulose promote
the formation of intramolecular hydrogen bonds
➢ Consequently, these molecules line up in linear arrays and intermolecular
hydrogen bonds form between adjacent chains
➢ These large aggregates cause cellulose to be insoluble in water
➢ The strength of these bundles of polymer chains makes cellulose an effective
structural material Intramolecular hydrogen bond

➢ All mammals have the enzyme (α-glucosidase) that hydrolyzes the

α-1,4’-glycosidic linkages that join glucose units, but they do not have the
enzyme (β-glucosidase) that hydrolyzes the β-1,4’-glycosidc linkages that join
glucose units
➢ Bacteria that possess β-glucosidase inhabit in the digestive tracts of grazing
animals assist herbivores to obtain their nutritional need
284
➢ Cellulose is structural material of higher plants
➢ Cotton, for example, is composed of about 90% cellulose, and wood is about
50% cellulose
➢ Like amylose, cellulose is composed of unbranched chains of D-glucose units
➢ Unlike amylose, however, the glucose units in cellulose are joined by
β-1,4’-glycosidic linkages rather than by α-1,4-glycosidic linkages

➢ Animals store their excess glucose in a polysaccharide known as glycogen

➢ Glycogen has a structure similar to that of amylopectin, but glycogen has
more branches
➢ The branch points in glycogen occur about every 10 residues, whereas those
in amylopectin occur about every 25 residues
➢ The high degree of branching in glycogen has important physiological effects,
When the body needs energy, many individual glucose units can be
simultaneously removed from the ends of many branches

285
➢ Chitin is a polysaccharide that is structurally similar to cellulose
➢ It is the major structural component of the shells of crustaceans (e.g.,
lobsters, crabs, and shrimps) and the exoskeletons of insects
➢ Like cellulose, chitin has β-1,4’-glycosidic linkages
➢ It differs from cellulose in that it has an N-acetylamino group instead of an
OH group at the C-2 position
➢ The β-1,4’-glycosidic linkages give chitin its structural rigidity

Only three subunits of chitin

286
➢ Chitin synthase inhibitors are used commercially as insecticides because they
prevent the formation of a new exoskeleton and the shedding of the old one
➢ The insect becomes trapped in an old exoskeleton that cannot grow
➢ These inhibitors are highly toxic to insects and crustaceans, but relatively
nontoxic to mammals
➢ The most common chitin synthase inhibitors are substituted benzoylureas
such as diflubenzuron, which was first registered as an insecticide in 1976

Cl
O
O
F C
NH NH

diflubenzuron or Dimlin ™
Lufenuron is used to kill fleas

287
➢ Glycoproteins
➢ The surfaces of many cells contain short polysaccharide chains that allow the
cells to interact with each other, as well as to interact with invading viruses
and bacteria
➢ These polysaccharides are linked to the cell surface by the reaction of an OH
or an NH group of a protein with the anomeric carbon of a cyclic sugar
➢ Proteins bonded to polysaccharides are called glycoproteins
➢ The percentage of carbohydrate in glycoproteins is variable; some
glycoproteins contain as little as 1% carbohydrate by weight, whereas others
contain as much as 80%
➢ Many different types of proteins are not pure proteins, they are glycoproteins
➢ For example, structural proteins such as collagen, proteins found in mucous
secretions, immunoglobulins, follicle-stimulating hormone and thyroid-
stimulating hormone, interferon (an antiviral protein), and blood plasma
proteins are all glycoproteins
➢ One of the functions of the polysaccharide chain is to act as a receptor site on
the cell surface in order to transmit signals from hormones and other
molecules across the cell membrane into the cell
➢ The carbohydrates on the surfaces of cells also serve as points of attachment
for other cells, viruses, and toxins in case of immunoglobulins
288
➢ Blood type (A, B, AB, or O) is determined by the nature of the polysaccharide
bound to the protein on the outer surfaces of red blood cells
➢ Each type of blood is associated with a different carbohydrate structure
➢ Type AB blood has the carbohydrate structure of both type A and B
➢ Antibodies are proteins that are synthesized by the body in response to a
foreign substance, called an antigen
➢ Interaction with the antibody either causes the antigen to precipitate or flags
it for destruction by immune system cells
➢ This is why, for example, blood cannot be transferred from one person to
another unless the carbohydrate portions of the donor and acceptor are
compatible
➢ The immune system of people with type A, B, or AB blood does not, however,
recognize type O blood as foreign, because the carbohydrate in type O blood
is also a component of types A, B, and AB blood

289
 OHOH
Fucose is 6-deoxygalactose
OH O OH GalNAc
OH
OHOH O CH3 HO OH O
HO O O OH
O O NH O OH OHOH O NH
HO O Gal HO OH O CH3
OH fuc O OH
GlcNAc OHOH O
Gal HO O CH3
O O
O O NH
HO OH
O antigen Gal OH O HO
Gal fuc
Gal GlcNAc
HO OH O
OHOH OH A antigen
OH O OH
O OH
O CH3
OHOH HO O
O O
O O NH OH
HO O HO
OH
Gal GlcNAc Gal fuc

B antigen

290
 HO OH O
OHOH OH
OH O OH
O OH
O CH3
OHOH HO O
O O
O O NH OH
HO O HO
OH
Gal GlcNAc Gal fuc

2,1-
B Gal -1,3 GlcNAC -1,3 Gal Fuc
B antigen
-1
, 3 Gal

➢ Thus, anyone can accept type O blood, so people with type O blood
are called universal donors while type AB people can accept types AB,
A, B, and O blood, so people with type AB blood are referred to as
universal acceptors

291
➢ Summary of major Function of carbohydrate
➢ Carbohydrates serve as energy stores (fuels), and metabolic intermediates
➢ Ribose and deoxyribose sugars form part of the structural framework of
RNA and DNA
➢ Polysaccharides are structural elements in the cell walls of bacteria and
plants
➢ In fact, cellulose, the main constituent of plant cell walls, is one of the
most abundant organic compounds in the biosphere
➢ Glycoproteins play key roles in mediating interactions among cells and
interactions between cells and other elements in the cellular environment
( recognition site, receptors, attachment site)

292
 ➢ 5.2 Fats and oils
➢ Lipids are naturally occurring molecules that have limited solubility in water and can
be isolated from organisms by extraction with a nonpolar organic solvent
➢ Fats, oils, waxes, many vitamins and hormones, and most nonprotein cell-
membrane components are examples of lipids
➢ Lipids are classified into two general types:
➢ Those like fats and waxes, which contain ester linkages and can be hydrolyzed,
and
➢ Those like cholesterol and other steroids, which don’t have ester linkages and
can’t be hydrolyzed

5.2.1 Fatty Acids

➢ The fatty acids most frequently found in nature are an even number of carbon
atoms and are unbranched because they are synthesized from acetate (see
the biosynthesis of fatty acid)

acetate

➢ Fatty acids can be saturated with hydrogen or Unsaturated with one or more
double bond

293
➢ Fatty acids with more than one double bond are called polyunsaturated
fatty acids
➢ Double bonds in naturally occurring unsaturated fatty acids are never
conjugated: they are always separated by one methylene group
➢ The physical properties of a fatty acid depend on the length of the
hydrocarbon chain and the degree of unsaturation
➢ As expected, the melting points of saturated fatty acids increase with
increasing molecular weight because of increased van der Waals
interactions between the molecules
➢ The double bonds in unsaturated fatty acids generally have the cis
configuration
➢ This configuration produces a bend in the molecules, which prevents them
from packing together as tightly as fully saturated fatty acids
➢ As a result, unsaturated fatty acids have fewer intermolecular interactions
and, therefore, lower melting points than saturated fatty acids with
comparable molecular weights
➢ The melting points of the unsaturated fatty acids decrease as the number
of double bonds increases
294
 ➢ Common Naturally Occurring saturated Fatty Acids

lauric acid (dodecanoic acid ) myristic acid ( tetradecanoic acid )

mpt = 44oc mpt = 58oc

palmitic acid (hexadecanoic acid) stearic acid (octadecanoic acid)

mpt =63oc mpt 69oc

arachidic acid (eicosanoic acid)

mpt = 77oc
➢ Common Naturally occurring unsaturated Fatty Acids

oleic acid [(9Z)-octadecenoic acid ]

palmitoleic acid [(9Z)-hexadecenoic acid] mpt =13oc
mpt = 0oc 295
linoleic acid [ (9Z,12Z)-octadecadienoic acid] linolenic acid [(9Z,12Z,15Z)-octadecatrienoic acid]
mpt = -5oc Mpt = -11oc

arachidonic acid [(5Z,8Z,11Z,14Z)-eicosatetraenoic acid EPA

Mpt = 50oc (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoic acid
Mpt = 50oc

➢ The melting points of the unsaturated fatty acids decrease as the number of
double bonds increases

296
5.2.2 Fats & Oils

➢ Triacylglycerols, also called triglycerides, are compounds in which the three

OH groups of glycerol are esterified with fatty acids
➢ If the three fatty acid components of a triacylglycerol are the same, the
compound is called a simple triacylglycerol
➢ Mixed triacylglycerols, on the other hand, contain two or three different
fatty acid components and are more common than simple triacylglycerols
➢ Substances such as lard and olive oil, for example, are mixtures of several
different triacylglycerols

297
➢ Triacylglycerols that are solids or semisolids at room temperature are called
fats
➢ Fats are usually obtained from animals and are composed largely of
triacylglycerols with either saturated fatty acids or fatty acids with only one
double bond
➢ The saturated fatty acid tails pack closely together, giving the triacylglycerols
relatively high melting points, causing them to be solids at room
temperature
➢ Liquid triacylglycerols are called oils
➢ Oils typically come from plant products such as corn, soybeans, olives, and
peanuts
➢ They are composed primarily of triacylglycerols with unsaturated fatty acids
that cannot pack tightly together
➢ Consequently, they have relatively low melting points, causing them to be
liquids at room temperature
➢ Some or all of the double bonds of polyunsaturated oils can be reduced by
catalytic hydrogenation
➢ Margarine and shortening are prepared by hydrogenating vegetable oils
such as soybean oil and safflower oil until they have the desired consistency
in a process is called “hardening of oils”
298
 Hydrogenation
or hardening of oil a fat
Solid at room temperature

an oil
liquid at room temperature
299
➢ Vegetable oils have become popular in food preparation because some
studies have to be linked the consumption of saturated fats with heart
disease
➢ Recent studies have shown that unsaturated fats may also be implicated in
heart disease
➢ However, one unsaturated fatty acid—a 20-carbon fatty acid with five
double bonds, known as EPA and found in high concentrations in fish oils—is
thought to lower the chance of developing certain forms of heart disease
➢ Organisms store energy in the form of triacylglycerols
➢ A fat provides about six times as much metabolic energy as an equal weight
of hydrated glycogen because fats are less oxidized than carbohydrates and,
since fats are nonpolar, they do not bind water
➢ (fat: 1g = 9 calories, protein: 1g = 4 calories, anhydrous carbohydrate: 1g
= 4 calories and alcohol: 1g = 7 calories)
➢ In contrast, two-thirds of the weight of stored glycogen is water
➢ Animals have a subcutaneous layer of fat cells that serves as both an energy
source and an insulator
➢ The fat content of the average man is about 21%, whereas the fat content of
the average woman is about 25% of their body weight

300
➢ 5.2.3 Waxes
➢ Waxes are esters formed from long-chain carboxylic acids and long-chain
alcohols
➢ For example, beeswax, the structural material of beehives, has a 16-carbon
carboxylic acid component and a 30-carbon alcohol component
➢ Carnauba wax is a particularly hard wax because of its relatively high
molecular weight, arising from a 32-carbon carboxylic acid component and a
34-carbon alcohol component
➢ Carnauba wax is widely used as a car wax and in floor polishes and candle
➢ Waxes are common in living organisms
➢ The feathers of birds are coated with wax to make them water repellent
➢ Some vertebrates secrete wax in order to keep their fur lubricated and water
repellent
➢ Insects secrete a waterproof, waxy layer on the outside of their exoskeletons
➢ Wax is also found on the surfaces of certain leaves and fruits, where it serves
as a protectant against parasites and minimizes the evaporation of water

301
➢ Triacontyl hexadecanoate (from beeswax); structural material of beehives

➢ A major component of carnauba wax (coating on the leaves of a Brazilian

palm)

➢ A major component of spermaceti wax from the heads of sperm whales

302
5.2.4 Phospholipids (Membranes)
➢ “Greasy” lipid membranes serve as the barrier b/n different compartment of
the cell and the cell contents from extracellular fluids
➢ In addition to isolating the cell’s contents, these membranes allow the
selective transport of ions and organic molecules into and out of the cell
➢ Phosphoacylglycerols ( phosphoglycerides) are the major components of cell
membranes
➢ They are similar to triacylglycerols except that a terminal OH group of glycerol
is esterified with phosphoric acid rather than with a fatty acid, forming a
phosphatidic acid
➢ Because phosphoacylglycerols are lipids that contain a phosphate group, they
are classified as phospholipids
➢ The C-2 carbon of glycerol in phosphoacylglycerols has the R configuration

303
➢ Phosphatidic acids are the simplest phosphoacylglycerols and are present only
in small amounts in membranes
➢ The most common phosphoacylglycerols in membranes have a second
phosphate ester linkage
➢ The alcohols most commonly used to form this second ester group are
ethanolamine, choline, and serine
➢ Phosphatidylethanolamines are also called cephalins, and
phosphatidylcholines are called lecithins
➢ Used as emulsifying agents, lecithins are added to foods such as mayonnaise
to prevent the aqueous and fat components from separating
➢ Phosphoacylglycerols form membranes by arranging themselves in a lipid
bilayer
➢ The polar heads of the phosphoacylglycerols are on the outside of the bilayer,
and the fatty acid chains form the interior of the bilayer
➢ Cholesterol—a membrane lipid is also found in the interior of the bilayer

304
 hydrophilic
The structure of lipid bilayer

Hydrophobic

➢ The fluidity of a membrane is controlled by the fatty acid components of the

phosphoacylglycerols
➢ Saturated fatty acids and cholesterol decrease membrane fluidity because
their hydrocarbon chains can pack closely together
➢ Unsaturated fatty acids increase fluidity because they pack less closely
together
➢ Only animal membranes contain cholesterol, so they are more rigid than
plant membranes

305
 H a phosphatidic acid
H H
HO
cholesterol

a phosphatidylethanolamine a phosphatidylcholine a phosphatidylserine

a cephalin a lecithin
306
➢ Sphingolipids
➢ Sphingolipids are also found in membranes (neural membrane)
➢ They are the major lipid components in the myelin sheaths of nerve fibers
➢ Sphingolipids contain sphingosine instead of glycerol
➢ In sphingolipids, the amino group of sphingosine is bonded to the acyl group
of a fatty acid
➢ Both asymmetric carbons in sphingosine have the S-configuration
➢ Two of the most common kinds of sphingolipids are sphingomyelins and
cerebrosides
➢ In sphingomyelins, the primary OH group of sphingosine is bonded to
phosphocholine or phospho ethanolamine, similar to the bonding in lecithins
and cephalins

Sphingosine is long-chain amino alcohol

307
 β-glycosidic bond

a sphingomyelin (lecithin)
a glucocerebroside
➢ In cerebrosides, the primary OH group of sphingosine is bonded to a sugar
residue through a β-glycosidic linkage
➢ Sphingomyelins are phospholipids because they contain a phosphate group
➢ Cerebrosides, on the other hand, are not phospholipids

308
5.2.5 Prostaglandins
➢ Prostanoids comprise a family of lipid mediators formed from arachidonic acid
(AA)
➢ Prostanoids include prostaglandins (PGs), prostacyclins (PGIs), and
thromboxanes (TXs)
➢ Prostaglandins exist in virtually every mammalian tissue, acting as local
hormones
➢ They are synthesized in vivo by cyclization of the center of the carbon chain
of 20-carbon (eicosanoic) polyunsaturated fatty acids to form a cyclopentane
ring
➢ Prostaglandins act in many tissues by regulating the synthesis of the
intracellular messenger 3’,5’-cyclic AMP (cAMP)

309
Prostaglandins affect
✓blood pressure,
✓ blood clotting,
✓ gastric secretion,
✓ kidney function,
✓ inflammation,
✓ uterine contractility,
✓ the wake-sleep cycle, and the responsiveness of certain tissues to
hormones such as epinephrine and glucagon
➢ Prostaglandins of a third group elevate body temperature (producing fever)
and cause inflammation and pain
➢ in particular, prostaglandins (PGE1) is a potent pyrogen (fever-inducing
agent), involved in the symptoms of many pathological processes
➢ Structurally, all prostaglandins have
✓ a five-membered ring with a seven-carbon carboxylic acid substituent and
✓ an eight carbon hydrocarbon substituent

310
➢ The two substituents on the ring are trans to each other
➢ Prostaglandins are classified using the formula PGX, where X designates the
functional groups of the compound’s five-membered ring
✓ PGAs, PGBs, and PGCs all contain a carbonyl group and a double bond in
the five-membered ring
✓ PGDs and PGEs are β-hydroxy ketones
✓ and PGFs are 1,3-diols
➢ A subscript indicates the total number of double bonds in the side chains, α
and β indicate the configuration of the two OH groups in a PGF:
✓ indicates α cis diol and β indicates a trans diol

H
COOH

prostaglandin skeleton
3’,5’-cyclic AMP
311
Structures of PG
O
H

R1
H R2
PGAs

PGA2

312
➢ Prostaglandins are synthesized from arachidonic acid, a 20-carbon fatty acid
with four cis double bonds
➢ In the cell, arachidonic acid is found esterified to the 2-position of glycerol in
many phospholipids
➢ An enzyme called prostaglandin endoperoxide synthase catalyzes the
conversion of arachidonic acid to PGH2 the precursor of all prostaglandins
➢ Prostaglandins, prostacyclin, and thromboxane are considered autocoids,
synthesized in many different organs and acting locally
➢ There are two forms of this enzyme;
✓ one carries out the normal physiological production of prostaglandin,
and
✓ the other synthesizes additional prostaglandin in response to
inflammation
➢ The enzyme has two activities: a cyclooxygenase activity and a
hydroperoxidase activity

313
 biosynthesis of prostaglandins, thromboxanes, and prostacyclins
O

O
HO
H H
HO
cyclooxygenase
H
arachidonic acid
O

O O
H
O
COOH
HO
O
H O
H
O
OOH
HO O
hydroperoxide a peroxy radical

cyclooxygenase activity

314
315
➢ PGH2 is also precursor for the synthesis of thromboxanes and prostacyclins
✓ Thromboxanes constrict blood vessels and stimulate the aggregation of
platelets, the first step in blood clotting
✓ Prostacyclins have the opposite effect, dilating blood vessels and inhibiting
the aggregation of platelets
➢ The levels of these two compounds must be carefully controlled to
maintain the proper balance in the blood
➢ Aspirin (acetylsalicylic acid) inhibits the cyclooxygenase activity of
prostaglandin endoperoxide synthase
➢ It does this by transferring an acetyl group to a serine hydroxyl group of the
enzyme
➢ Aspirin, therefore, inhibits the synthesis of prostaglandins and, in that way,
decreases the inflammation produced by these compounds
➢ Aspirin also inhibits the synthesis of thromboxanes and prostacyclins

316
➢ Overall, this causes a slight decrease in the rate of blood clotting, which is
why some doctors recommend one aspirin tablet every other day to reduce
the chance of a heart attack or stroke caused by clotting in blood vessels
➢ Other anti-inflammatory drugs, such as ibuprofen and naproxen also inhibit
the synthesis of prostaglandins

317
➢ Both aspirin and these other nonsteroidal anti-inflammatory drugs (NSAIDs)
inhibit the synthesis of all prostaglandins including those produced under
normal physiological conditions and those produced in response to
inflammation
➢ The production of acid in the stomach is regulated by a prostaglandin
➢ When prostaglandin synthesis stops, therefore, the acidity of the stomach
can rise above normal levels
➢ Recently drugs Celebrex® and Vioxx® have become available inhibit only the
enzyme that produces prostaglandin in response to stress
➢ Thus, inflammatory conditions now can be treated without some of the
harmful side effects

ibuprofen
aspirin naproxen

318
celebrex VOXX

319
➢ Arachidonic acid can also be converted into a leukotriene
➢ Leukotrienes induce contraction of the muscle that lines the airways to
the lungs, leukotrienes are implicated in allergic reactions, inflammatory
reactions, and heart attacks
➢ Leukotrienes also bring on the symptoms of asthma and are implicated in
anaphylactic shock, a potentially fatal allergic reaction
➢ But there are several antileukotriene agents available for the treatment of
asthma

320
 ➢ Prostaglandins: Pharmacological Effects
➢ Oxytocic Activity
➢ The oxytocic activity of prostaglandins is used clinically
➢ Prostaglandin E2 can induce labor at term in pregnant women, while PGF2
and its methyl ester are used for terminating pregnancies in the second
trimester when administered by the intrauterine (intraamniotic) route
➢ The activity of PGF2 and its ester is probably due to a direct effect on uterine
muscle, since in late pregnancy progesterone is already being produced by
the placenta rather than by the corpus luteum
➢ In earlier pregnancy, the PGF2 causes abortion by luteolysis and a decreased
production of progesterone
➢ Abortions initiated in this way are safe, but gastrointestinal side effects
(vomiting, diarrhea) are not uncommon

321
➢ Successful derivatives were mainly found among the 15- and 16-methyl
PGF2 and PGE1 analogs:
➢ Carboprost possesses very high uterotonic activity and is used to induce
abortions
➢ It probably inhibit the dehydrase that inactivates the prostaglandins by
removing the 15-OH group
➢ Misoprostol is a modified prostaglandin PGE1 analog that shows potent
gastric antisecretory and gastroprotective effects, it has been used to treat
and prevent gastric ulcers
Abortion pill is the common
name for using two different
medicines to end a
pregnancy: mifepristone and
misoprostol.

Misoprostol, PGE1 analog

Carboprost, PGF2 analog

322
 Summary of prostaglandins and related organic compound
PGD2 Weak inhibitor of platelet aggregation

PGE1 Bronchodilatation, inhibitor of fat breakdown, inhibitor of platelet

aggregation, stimulates contraction of gastrointestinal smooth muscle,
and vasodilation
PGE2 Elevates body temperature set-point in anterior hypothalamus, protects
stomach lining acid degradation, reduces secretion of stomach acid, renal
vasodilatation in kidneys, and stimulates uterine smooth-muscle
contraction
PGF2 Stimulates uterine smooth-muscle contraction

PGl2 Potent inhibitor of platelet aggregation and Potent vasodilator

(prostacyclin)
PGJ2 Inhibits cell proliferation and Stimulates osteogenesis (bone formation)
TXA2 Potent inducer of platelet aggregation, Potent vasoconstrictor, and
(thromboxane) Stimulates release of serotonin from platelets

323
5.2.6 Terpenes
➢ Terpenes are a diverse class of lipids, more than 20,000 terpenes are known
➢ They can be hydrocarbons, or they can contain oxygen and be alcohols,
ketones, or aldehydes
➢ Oxygen-containing terpenes are sometimes called terpenoids
➢ Certain terpenes and terpenoids have been used as spices, perfumes, and
medicines for many thousands of years
Examples:

324
➢ After analyzing a large number of terpenes, organic chemists realized that
they contained carbon atoms in multiples of 5
➢ These naturally occurring compounds contain 10, 15, 20, 25, 30, and 40
carbon atoms, which suggests that there is a compound with five carbon
atoms that serves as their building block
➢ Further investigation showed that their structures are consistent with the
assumption that they were made by joining together isoprene units, usually in
a head-to-tail fashion
➢ The branched end of isoprene unit is called the head, and the unbranched
end is called the tail
➢ Isoprene is the common name for 2-methyl-1,3-butadiene, a compound
containing five carbon atoms.
➢ This isoprene units are linked in a head-to-tail fashion to form terpenes is
known as the isoprene rule

carbon skeleton of two isoprene units with a

bond between the tail of one and the head of
another
325
➢ In the case of cyclic compounds, the linkage of the head of one isoprene unit
to the tail of another is followed by an additional linkage to form the ring
➢ The second linkage is not necessarily head-to-tail, but is whatever is
necessary to form a stable five- or six membered ring

a sesquiterpene found in the waxy coating on apple

skins

➢ The actually monomer used in the biosynthesis of terpenes is not isoprene,

but isopentenyl pyrophosphate, a compound that has the same carbon
skeleton as isoprene

326
➢ Terpenes are classified according to the number of carbons they contain
➢ Monoterpenes are composed of two isoprene units, so they have 10
carbons
➢ Sesquiterpenes, with 15 carbons, are composed of three isoprene units
➢ Many fragrances and flavorings found in plants are monoterpenes and
sesquiterpenes which are known as essential oils

Classification of terpenes

No carbon Name of terpene No. carbon Name the terpene

10 monoterpene 25 sesterterpenes

15 sesquiterpenes 30 triterpenes

20 diterpenes 40 tetraterpenes

327
Example:
➢ Carvone (spearmint oil) is a monoterpene

➢ Triterpenes (six isoprene units) and tetraterpenes (eight isoprene units) have
important biological roles
➢ For example, squalene, a triterpene, is a precursor of steroid molecules

328
➢ Carotenoids are tetraterpenes
➢ Lycopene, the compound responsible for the red coloring of tomatoes and
watermelon, and
➢ β-Carotene the compound that causes carrots and apricots to be orange, are
examples of carotenoids
➢ β-Carotene is also the coloring agent used in margarine
➢ β-Carotene and other colored compounds are found in the leaves of trees,
but their characteristic colors are usually obscured by the green color of
chlorophyll
➢ In the fall, when chlorophyll degrades, the colors become apparent
➢ The many conjugated double bonds in lycopene and β-Carotene cause the
compounds to be colored
lycopene

β-carotene

329
➢ Vitamins A, D, E, and K are lipids
➢ β-Carotene which is cleaved to form two molecules of vitamin A, is the major
dietary source of the vitamin
➢ Vitamin A, also called retinol, plays an important role in vision
CH2OH

retinol
vitamin A

➢ Biosynthesis of Terpenes
➢ Biosynthesis of Isopentenyl Pyrophosphate
➢ The five-carbon compound used for the biosynthesis of terpenes is
3-methyl-3-butenylpyrophosphate, loosely called isopentenyl pyrophosphate by
biochemists
➢ Each step in its biosynthesis is catalyzed by a different enzyme

330
 biosynthesis of isopentenyl pyrophosphate

acetyl-CoA malonyl-CoA acetoacetyl-CoA

Aldol condensation
followed by reduction

Esterification reduction
Mevalonyl phosphate by SN2
mevalonic acid hydroxymethylglutaryl-CoA
SN2 ATP is used to convert the OH group into a phosphate group, which is easily
eliminated because it is a weak base

Decaboxylation
and elimination
Isopentenyl
mevalonyl pyrophosphate pyrophosphate 331
➢ Biosynthesis of Dimethylallyl Pyrophosphate
➢ Both isopentenyl pyrophosphate and dimethylallyl pyrophosphate are
needed for the biosynthesis of terpenes
➢ Therefore, some isopentenyl pyrophosphate is converted to dimethylallyl
pyrophosphate by an enzyme-catalyzed isomerization reaction

isopentenyl pyrophosphate dimethylallyl pyrophosphate

dimethylallyl isopentenyl
pyrophosphate pyrophosphate
-H+
Geranyl
pyrophosphate
332
➢ The following scheme shows how some of the many monoterpenes could be
synthesized from geranyl pyrophosphate

geranyl geraniol citronellol

pyrophosphate in rose and in rose and citronellal
geranium oils geranium oils in lemon oil

terpin hydrate
a common constituent of cough medicine
α-terpineol
in juniper oil

limonene menthol
in orange and in peppermint oil
lemon oils
333
➢ Geranyl pyrophosphate can react with another molecule of isopentenyl
pyrophosphate to form farnesyl pyrophosphate, a 15-carbon compound

geranyl pyrophosphate isopentenyl pyrophosphate deprotonation

farnesyl pyrophosphate farnesyl pyrophosphate

squalene synthase
tail to tail

squalene

➢ Squalene is the precursor of cholesterol, and cholesterol is the

precursor of all other steroids
334
335
5.2.7 Steroids
➢ Hormones are central to homeostasis since they facilitate chemical control
over metabolic and biochemical processes throughout the entire body
➢ The endocrine system, which exerts control over chemical processes via
hormones, is crucial to homeostasis over an intermediate time scale
➢ The endocrine system is distinct from the nervous system, which employs
neurotransmitters to control electrical and electrochemical processes and to
influence homeostasis over a shorter time scale
➢ Hormones are synthesized from a wide variety of chemical building blocks
➢ The steroid hormones are synthesized from cholesterol
➢ Cholesterol is mostly derived from the plasma, but a small portion is
synthesized in situ from acetyl-CoA via mevalonate and squalene
➢ Steroid hormones are small organic molecules based on the four-ring steran
carbon skeleton

336
➢ Cholesterol is precursor for glucocorticoids, mineralocorticoids, estrogens,
progestins, bile mixture and 1,25(OH)2-D3 (vitamin D)

1,25(OH)2-D3 (vitamin D)

➢ All steroids are based on the steran skeleton, a fully hydrogenated cyclo
pentanophenanthrene

337
➢ Traditionally, the rings of this skeleton are labeled A, B, C, and D
➢ All four rings are in the chair conformation in naturally occurring steroids;
additionally, rings B, C, and D are always trans with respect to each other,
whereas rings A and B can be trans as in cholestane, or cis in coprostane

Cholestan, A and B are trans

Coprostane, A and B are cis

➢ Ergosterol is the predominant membrane sterol lipid in fungi; cholesterol is

the principal sterol in mammal cells

H H
HO
ergosterol 338
➢ Bile is made from cholesterol and stored in gallbladder

These gallstones, shown here within the

gallbladder, are composed mostly of cholesterol

339
➢ Steroid hormones are of two general types: adrenal cortex hormones (corticoids)
and sex steroid hormones
➢ Two classes of steroid hormones are synthesized in the cortex of the adrenal gland:
✓Mineralocorticoids, which control the reabsorption of inorganic ions (Na+, Cl-,
and HCO3 - ) by the kidney to maintain electrolyte balance and regulate blood
pressure
✓Glucocorticoids, are involved in glucose, protein and lipid metabolism
✓They regulate gluconeogenesis and reduce the inflammatory response such
as arithritis
➢ Sex steroid hormones are generally responsible for secondary sexual characteristics
➢Female sex hormone which are secreted by ovaries and collectively known as
estrogens
✓ They are involved with female secondary sexual characteristics and
regulate menstrual cycle
✓ Some of them are needed to maintain pregnancy and to avoid ovulation
during pregnancy
➢Male sex steroid hormones are collectively called androgens
✓ They are produced in tests and are involved for secondary male sexual
characteristics and muscle growth

340
 Female sex hormone
➢ Estrone, estradiol, and estriols are the common estrogens
➢ Structurally in all the three, the “A” ring is aromatic and 19th methyl is
absent, i.e., all are based on 18 carbons
➢ Progesterone has aceto substituent at C17 and the “A” ring is rather ‘enone’
➢ It has 19 methyl at 10th carbon and has ketone functional group at 20th
carbon

Estrone Estradiol Estriol

It helps pregnant uterus grow and stay
healthy. It also prepares as their body for
childbirth and breastfeeding
341
 ➢ Through its feedback effect on the hypothalamus,
progesterone prevents ovulation and also stops uterine
contraction
➢ luteinizing hormone is a hormone released by the
pituitary gland that causes the ovary to produce one or
more eggs, secrete progesterone, and form the corpus
luteum, and causes the tests to secrete male sex
progesterone hormones

➢ The corpus luteum is a vital yet temporary organ that plays a crucial role in
fertility during the luteal phase
➢ It is an endocrine structure in females existing within the ovary once the
ovarian follicle has released a mature ovum during ovulation
➢ Today, a variety of therapeutic estrogens (agonists and antagonists ) are
produced semisynthetically from estrogen intermediates synthesized from
diosgenin and other natural precursors

diosgenin
342
 ➢ Two semisynthetic, orally active estrogens are ethinyl estradiol and its 3-
methyl ether mestranol (Both of these are used in oral contraceptives )
➢ Quinestrol is another semisynthetic estrogen
➢ The most important property of the semisynthetic estrogens is their
increased oral effectiveness

Ethinyl estradiol menstralon quinestrol

➢ To achieve inhibition of ovulation, a progestogen analog and an oral estrogen (e.g.,
ethinyl estradiol, mestranol) are combined in varying amounts and/or at varying
times during the menstrual cycle
➢ The desired contraceptive effect is due to inhibition of ovulation through the
hypothalamo-pituitary mechanism: inhibiting maturation of ovarian follicles and
preventing ovulation
343
➢ The main use of progestins is based on their antifertility effect
➢ Since progesterone is poorly absorbed, it cannot be given orally
➢ An acetylenic compound prepared from androsterone, was an orally active
progestin, but also had male hormone action
➢ In subsequent work, a large number of semisynthetic progesterone
derivatives (progestogens) were synthesized (levonorgestrel, desogestrel,
norethindrone , norgestrel, and ethynodiol are found their principal use in
oral contraceptive formulations

norethindrone
levonorgestrel desogestrel

344
➢ Male Sex Hormones
➢ Testosterone and androsterone are the two most important male sex
hormones, or androgens
➢ Androgens are responsible for the development of male secondary sex
characteristics during puberty and for promoting tissue and muscle growth
➢ Both are synthesized in the testes from cholesterol

Testosterone
Androsterone

345
➢ The potent physiological effects of steroids led scientists, in their search for
new drugs, to synthesize steroids that are not available in nature and to
investigate their physiological effects
➢ Stanozolol and Dianabol are drugs developed in this way
➢ They have the same muscle-building effect as testosterone
➢ These drugs are available by prescription and are used to treat people suffering
from traumas accompanied by muscle deterioration and have been
administered to athletes and racehorses to increase their muscle mass
➢ Androstenedione is another minor hormone that has received particular
attention because of its use by prominent athletes

Androstenedione

346
➢ When anabolic steroids, used in excess are not without side effects
✓ In men, excessive use leads
✓ to a decrease in the secretion of testosterone,
✓ to testicular atrophy, and
➢ sometimes to breast enlargement (gynecomastia) if some of the excess
androgen is converted into estrogen
➢ In women, excess testosterone causes
✓a decrease in ovulation and estrogen secretion;
✓it also causes breast regression and
✓ growth of facial hair

347
➢ ADRENOCORTICOIDS (ADRENAL STEROIDS) Hormone
➢ The adrenal gland is a cap-like organ sitting at the upper pole of the kidney
➢ The outer adrenal cortex of adrenal gland secretes corticosteroid hormones:
(glucocorticoids and mineralocorticoids)
➢ The inner adrenal medulla secretes the catecholamine neurotransmitters:
epinephrine (adrenaline) and norepinephrine (noradrenaline)
➢ Glucocorticoids have important metabolic effects on carbohydrates, proteins,
and lipids; they stimulate phosphoenolpyruvate carboxykinase, glucose-6-
phosphatase, and glycogen synthase [enzyme activation]
➢ On the basis of biochemical effects, the two groups of corticosteroids can be
readily distinguished:
➢ They have oxygen at C11 as point of difference from sex steroids whose
hydroxylation deserves mitochondrial hormone
➢ C21 hydroxylation is needed for both mineralocorticoid and glucocorticoid
activity

348
➢ GLUCOCORTICOIDS
➢ The activity of glucocorticoids are based on two natural hormones, cortisol and
corticosterone
➢ Glucocorticoids (such as cortisol) promote gluconeogenesis and the formation of
glycogen, enhance the degradation of fat and protein, and inhibit the
inflammatory response
➢ They enable animals to respond to stress indeed, the absence of glucocorticoids
can be fatal
➢ The characteristic structural features of these hormones are the conjugated
3-ketone, the 11-OH group, and the l7β-ketol side chain
➢ Molecular modifications have been aimed at deriving compounds with
glucocorticoid (and anti-inflammatory) actions but lacking in mineralocorticoid
effects and other side effects

cortisol corticosterone 349

➢ MINERALOCORTICOIDS
➢ Mineralocorticoids are another kind of adrenocorticoid
➢ Mineralocorticoids (primarily aldosterone) act on the distal tubules of the
kidney to increase the reabsorption of Na+ , Cl-, and HCO3- and the excretion
of K+ and H+, which leads to an increase in blood volume and blood pressure
➢ Structurally, aldosterone differs from glucocorticoids in having an 18-
aldehyde group and lacking the 17α-OH??
➢ Most mineralocorticoids are also have hydroxyl at the 21st carbon which
seems important for action
➢ The aldehyde participates in a tautomeric equilibrium, forming a cyclic
hemiacetal ring

aldosterone
350
➢ Pharmacological Activity of Glucocorticoids:
➢ The most important clinical application of glucocorticoids and their
semisynthetic analogs is their anti-inflammatory activity
➢ Glucocorticoids suppress inflammation at the cellular level by downregulating
the concentration, distribution, and function of leukocytes
➢ Glucocorticoids also suppress inflammation at the molecule level by
suppressing inflammatory cytokines, chemokines, and other molecular
mediators of inflammation
➢ Anti-inflammatory glucocorticoids have also been used to suppress
pathological inflammation in various organ systems, including the heart
(myocarditis, pericarditis), lungs (pneumonitis, allergic bronchitis, asthma),
bowel (regional ileitis), and skin (dermatitis)
➢ But side effects of steroid use include loss of blood glucose control in a
known diabetic, initiation of diabetes in a previously nondiabetic person,
worsening of infections (especially bacterial or fungal infections), psychiatric
problems (psychosis, hypomania, or depression), peptic ulcers, hypokalemia
(low potassium in the blood)

351
➢ Only some glucocorticoid agonists are used to treat inflammation but not
infection
➢ Prednisone and prednisolone are commonly employed for allergic related
inflammation

Triamcinolone is used only

Prednisone
for treatment of skin, oral,
and joint inflammations

352
Biosynthesis of cholesterol optional
O

CH3 C S-CoA
CoA-SH
O O O CoA-SH
OH O
CH3 C CH3 C CH2 C
O2CCH2 C CH2 C
S-CoA S-CoA
S-CoA
CH3
acetyl-CoA AcetoacetylCoA
3-Hydroxy-3-methylglutaryl-CoA
2NADPH + 2H+

2NADP+
CoA-SH
OH O ATP
ADP
OOC H2C C H2C CH2 O P OH
O OOC H2C C H2C CH2 OH
CH3 O
5-Phosphomevalonate CH3
ATP Mevalonate
ATP
ADP ADP CH3 O O
OH O O
OOC H2C C H2C CH2 O P O P
OOC H2C C H2C CH2 O P O P O O
O O O O
CH3 O O
P O
O
5-Pyrophosphomevalonate 3-Phospho-5-pyrophosphomevalonate 353
CO2 + Pi CH3 O O CH3 O O
CH2 C H2C CH2 O P O P CH3 C CH CH2 O P O P
O O
O O O
O
3-Isopentenyl pyrophosphate
Dimethylallyl pyrophosphate

354
355
356