Pharmaceutical

Biochemistry-II (PD-310)
DR. Hira
Assistant Professor
Dept. of Pharmacology
Dow University of Health Sciences
LIPIDS

DR. HIRA
Dept. of
Pharmacology
DUHS
Objectives
• By the end of these lectures, students will be able to learn;
• Lipids and their biological and pharmaceutical roles.
• Classification of fatty acids and their chemical reaction.
• Classification of other lipids
• Essential and non-essential fatty acids in the body
• Basic structure of simple, Complex and Precursor/Derived lipids
• Digestion and absorption of lipids
LIPIDS
• Any member of a large and diverse group of oils, fats, and fat like
substances that occur in living organisms and that
characteristically are soluble in organic solvents but only
sparingly soluble in aqueous solvents.
• Lipids are not polymers, but mostly small molecules.
• Most membrane lipids are amphipathic, having a non-polar end
and a polar end.
• The lipids are a heterogeneous group of naturally occurring
compounds; including fats, oils, steroids, waxes, and related
compounds, that are related more by their physical than by their
chemical properties.
Biological Importance
 Storage form of energy
 Important dietary components because of their high energy value
and also because of the fat- soluble vitamins and the essential fatty
acids contained in the fat of natural foods.
 Structural components of biological membranes
 Serve as thermal insulators in the subcutaneous tissues and
around certain organs
 Nonpolar lipids act as electrical insulators, allowing rapid
propagation of depolarization waves along myelinated nerves
 Provide shape and contour to the body
 Act as metabolic regulators
 Combinations of lipid and protein (lipoproteins) are important
cellular constituents, occurring both in the cell membrane and in
the mitochondria, and serving also as the means of transporting
lipids in the blood.
Pharmaceutical Importance
• Lipids play important roles in the absorption of fat-soluble nutrients; i.e.,
essential fatty acids (omega-3 and omega-6), fat-soluble vitamins, cellular
transport components, and food/medical supplements.
• The Omega-3 fatty acids have important roles in human health i.e., reducing
plasma triglycerides and in managing the risk of cardiovascular diseases.
• Lipids play an essential role in processing quality, and the organoleptic and
texture properties of food products.
• Many vegetable oils are used as excipients; almond oil, apricot oil, avocado
oil, borage oil, coffee oil, saf flower oil, etc.; from the animal source, f ish oil
and bird oil can be employed as excipients ( vehicle or medium) in
cosmetical formulations. Fats and waxes may be also used for this purpose.
• Phospholipids are suitable for use in cosmetics, pharmaceuticals and
diagnosis purpose.
• These substances are used as vehicle for therapeutic substances, such as
liposomes.
• Carotenoids, retinoids, tocopherols are used for their antioxidant properties,
that are important to health and diagnostic medicine.
 Classification of LIPIDS
1. Based on their reactivity with strong bases.
• Saponification is a process involving the hydrolysis of fats on its reaction
with alkali, thereby leading to the formation of salts of fatty acids and
glycerol (The salts of fatty acids are known as soap).
• contain long chain carboxylic (of fatty) acids,
that are linked to an alcoholic functional
group through an ester linkage. Example
Saponifiable • Triglycerides
lipids • Waxes
• Phospholipids
• Sphingolipids
Nonsaponifiabl • do not contain ester groups, and cannot be
e saponified (steroids, prostaglandins, "fat-
Lipids soluble" vitamins (A, E)
Classification of LIPIDS

Derived Lipids

Oil/Fats
Classification Of LIPIDS

2. Based on the chemical composition
Lipids

Simple Complex Derived

1. Wax esters 1. Fatty acids
2. Triacylglycerol 2. Sterols
(fats/oils) 3. Diglycerides
Phospholipids Glycolipids 4. monoglycerides
1.Cerebrosides
2.Gangliosides

Glycerophospholipids Sphingolipids
1.Phosphatidylcholine (PC) 1.Ceramides
2.Phosphatidylethanolamine (PE) 2.Sphingomyelin
3.Phosphatidylinositol (PI)
 Classif ication
• The lipids are classif ied as
1. Simple lipid
2. Complex lipid
3. Precursor and derived lipid
1. Simple lipids
• Esters of fatty acids with various alcohols.
a. Triacylglycerol (Fats and Oils): Fats are esters of fatty acids
with glycerol (solid at room temperature). Oils are fats in the
liquid state.
b. Waxes: Esters of fatty acids with higher molecular weight
monohydric alcohols.
FATTY ACIDS
• Fatty Acids are long hydrocarbon side chains with carboxylic
acids containing molecules.

• Usually contains an even number of carbon atoms ranging from

4C- 36C.
• Chain may be saturated (containing no double bonds) or
unsaturated (containing one or more double bonds)
• It occurs mainly in esterif ied form.
• Fats of animal origin are simpler than that of plant origin.
• Palmitic acid and stearic acid – most common
Nomenclature of Fatty Acids
• Named after corresponding hydrocarbons.
• -oic being substituted for the f inal –e.
• Saturated acids end in -anoic,
– eg, octanoic acid,
• Unsaturated acids with double bonds end in
-enoic,
– eg, octadecenoic acid (oleic acid)
• Numbered from the carboxyl carbon (carbon No. 1). The carbon atom
adjacent to the carboxyl carbon (C, 2, 3, 4) are known as α, β, and γ
carbons respectively.
• Terminal methyl carbon is known asthe ω or n-carbon
• Δ for indicating the number and position of the double bond
• ω9 indicates a double bond on the ninth carbon counting from the ω- carbon
Classification of Fatty Acids
• Fatty acids can be classified on the basis of the
presence/absence of double bonds in the hydrocarbon tail:
1. Saturated fatty acids have only single bonds. Molecules that fit
closely together in a regular pattern. Strong attractions between
fatty acid chains and high melting points that make them solids
at room temperature.
2. Unsaturated Fatty Acids have one or more double bonds.
Nonlinear chains that do not allow molecules to pack closely,
hence liquid at room temperature
I. Monounsaturated fatty acids have one double bond
II. Polyunsaturated fatty acids have two or more double bonds
Major Saturated Fatty
Acids
Unsaturated Fatty Acids
• Fatty acids may be further subdivided as follows
– Monounsaturated (monoethenoid, monoenoic) acids, contain one
double bond.
– Polyunsaturated (polyethenoid, polyenoic) acids, contain two or more
double bonds.
– Essential Fatty Acids: The fatty acid can not be synthesized by the body
and therefore has to be supplied in the diet. Ex: Linoleic Acid (ω-6),
Linolenic Acid (ω-3). Arachidonic acid is formed from precursor linoleic
acid. Arachidonic acids are used to produce hormone-like substances
that regulate blood pressure, blood clotting, blood lipid levels, the
immune response, and inflammatory reactions.
– Non-Essential Fatty acids: can be synthesized in the body, palmitic acid,
stearic acid etc.
Major Unsaturated Fatty
Acids
TRIACYLGLYCEROLS
• Also known as triglycerides.
• Main storage form of fatty acids
• Esters of the trihydric alcohol glycerol
and fatty acids.
• Because the polar hydroxyls of glycerol
and the polar carboxylates of the fatty
acids are bound in ester linkages,
triacylglycerols are nonpolar,
hydrophobic molecules, essentially
insoluble in water.
TRIACYLGLYCEROLS
• Triacylglycerols are the major form of fatty acid storage in
plants and animals
• Triacylglycerols can be classified as fats or oils
- fats are solid at room temperature and most come from
animals
- oils are usually liquid at room temperature and come from
plants (palm and coconut oils are solids at room temperature)
Waxes
• Esters of long chain fatty Acids with long chain
alcohols
• Higher melting points
• Hydrophobic
Biological waxes consist of esters of long-chain fatty acids
with long chain alcohols.

Have very high melting points, function as energy stores,

and act as water-impermeable coatings.

Triacontanylpalmitate is the major component of

bees wax.
2. Complex lipids: Esters of fatty acids containing groups in
addition to an alcohol and a fatty acid.

a. Phospholipids: Lipids containing, in addition to fatty acids and an

alcohol, a phosphoric acid residue. They frequently have nitrogen-
containing bases and other substituents.
Glycerophospholipids/posphoglycerides the alcohol is glycerol
and in Sphingophospholipids the alcohol is sphingosine.

b. Glycolipids (glycosphingolipids): Lipids containing a fatty acid,

sphingosine, and carbohydrate.

c. Other complex lipids: Lipoproteins may also be placed in this

category.
3. Precursor and Derived Lipids: Sterols, Eicosanoids, Vitamin A, D,
E, and K.
I. Glycerophospholipids
• also called phosphoglycerides
• membrane lipids in which two fatty acids
are attached in ester linkage to the f irst and
second carbons of glycerol
• a highly polar or charged group is attached
through a phosphodiester linkage to the
third carbon
 Glycerophospholipids
• Glycerol is prochiral
– no asymmetric carbons
– But attachment of phosphate at one end converts it into a chiral
compound.
• Various important types of glycerophopholipids
– Phosphatidic acid
– Phosphatidylcholine (Lecithin)
– Phosphatidylethanolamine (Cephalin)
– Phosphatidylinositol
– Phosphatidylserine
– Plasmalogens
– Cardiolipin
i. Phosphatidylcholines
• Also known as lecithins
• Present in phospholipids of the cell membrane.
• Choline (part of neurotransmittor) – component of
lecithin
• Dipalmitoyl lecithin is a very effective surface active
agent - major constituent of the Surfactant
– Absence - premature infants causes respiratory distress
syndrome
ii. Phosphatidyl ethanolamine (cephalin)
•Structurally like Lecithin with the exception that the base
•Ethanolamine replaces choline
•Brain and nervous tissue are rich in Cephalin
iii. Cardiolipin
• Abundantly found in mitochondrial membrane of the heart tissues.
iv. Phosphatidylinositol
•Precursor of Second Messengers
•Phosphatidylinositol 4,5-bisphosphate -
•constituent of cell membrane phospholipids.
v. Ether Lipids
•Ether linkage instead of ester
at C1, Plasmalogens.
Vertebrated heart tissues
enriched in ether lipid
plasmalogens
•Platelet activating factor (PAF)
is another ether lipid
•PAF activates inf lammatory
cells and mediates
hypersensitivity, acute
inf lammatory and anaphylactic
reactions
•Causes platelets to aggregate
and neutrophils and alveolar
macrophages to generate
II. Sphingophospholipids
• Sphingosine is a combination acyl
chain & head group
HO-1CH-CH=CH-(CH2)12-CH3
2CH-NH3
3CH -OH
2

• Backbone is sphingosine
(amino alcohol instead of
glycerol)
• A long chain fatty acid is
attached to amino group of
sphingosine to form Ceramide
• Found in large quantities in
brain and nerve tissue.
 Head groups at C3
i.Phosphosphingolipid
• The alcohol group at
carbon-1of
sphingosine is
esterif ied to
phosphoryl choline,
producing
sphingomyelin
• Sphingomyelin is an
important component
of myelin of nerve
f ibers
b. Glycosphingolipids/
• Blood Groups
Glycolipids: Monosaccharide or • O,
oligosaccharide attached directly to • A (+GalNa
c),
ceramide by an O- glycosidic linkage.

• B (+Gal)
Cerebrosides have Glucose or
galactose; Globosides have simple
neutral Oligosaccharides;
Gangliosides have more complicated
anionic oligosaccharides. Widely
distributed in every tissue of the body,
particularly in nervous tissue such as
brain.


Glyco-sphingolipids specify cell
identity
3. Precursor and derived lipids
• Are compounds
produced when simple
and complex lipids
undergo hydrolysis.
• These include fatty acids,
steroids, prostaglandins,
fatty aldehydes, ketone
bodies, hydrocarbons,
lipid-soluble vitamins,
and hormones.
a. Steroids
• Compound containing
cyclic steroid nucleus
• Phenanthrene nucleus – A,
B,C
• Cyclopentane ring – D
• Several steroids in
biological systems
– Cholestrol
– Bile acids
– Vitamin D
– Sex Hormone
– Adrenocortical hormones
– Cardiac glycosides
– Alkaloids
 i. Sterols
• Steroid nucleus have 4
fused rings three with six
carbons and one with
five
• Cholesterol is the major
sterol in vertebrates
• Steroid Hormones
• Testosterone,
Estrogen
Cholesterol

• Properties
– Yellowish crystalline solid
– Insoluble in water and soluble in organic
solven
• Function
– Present in nervous tissues – insulating
cover
– Biochemical function – precursor for many
biochemical substances and component of
cell membrane
Digestion and
Absorption Of
Lipids
 The average intake of lipids
by US adults (78gm)i
s >90% triacylglycerols.
The other are
Cholesterol
Cholesteryl esters
Phospholipids
Unesterified fatty acids.
 Digestion starts in mouth
followed by stomach with
t he he lp o f ling ua l a nd
gastric lipases.
 These lipases hydrolyze
fatty acids from
triacylglycerols, particularly
sho r t o r m e d ium cha in
length.


Emulsification

 Lipids are hydrophobic, and thus are poorly soluble
in the aqueous environment of the digestive tract.
 The digestive enzyme, lipase, is water soluble and
can only work at the surface of fat globules.
 Digestion is greatly aided by emulsif ic ation, the
breaking up of fat globules into much smaller
emulsion droplets.
 Emulsification and Digestion
• Emulsif ication is the process of breaking down of large
fat globules into uniform tiny droplets.
• It is accomplished by detergent properties of bile salts
and peristalsis (mechanical mixing) emulsif ication
• It occurs in duodenum
• Emulsif ic ation decreases the surface tension and
increases the surface area of fat globules and thereby
lipolytic enzymes (lipase) can hydrolyze lipids
 Digestion in Small Intestine
 Major site of fat digestion
 Effective digestion due to the presence of Pancreatic
lipase and bile salts.
 Bile salts act as an effective emulsifying agents for
fats
 Secretion of pancreatic juice is stimulated by-

 Passage of acid gastric contents in to the duodenum

 By secretion of Secretin, Cholecystokinin and Pancreozymin,
the gastro intestinal hormones
 Gastrointestinal Hormones
Secretin- It releases in response to low pH of
chyme which enters intestine from stomach. It
stimulates the secretion of bicarbonates that
helps neutra lize the pH o f intes tina l
components.
Cholecystokinin (CCK)- causes the contraction
of the gall bladder and discharges the bile (a
mixture of bile salts, phospholipids and free
cholesterol) in to the duodenum.
 Contents of Pancreatic Juice
 Pancreatic Lipase- for the digestion of Triglycerides.
 Phospholipase A2- for the digestion of
Phospholipids.
 C h o l e s te r o l e s te ras e - f o r th e d i g e s ti o n o f
Cholesteryl esters.
Bile Salts
 Bile salts are synthesized in the liver and stored in the gall bladder
 They are derivatives of cholesterol
 They consist of a sterol ring structure with a side chain to which a
molecule of glycine or Taurine is covalently attached by an amide
linkage
 Bile salts are required for the proper functioning of the pancreatic
lipase enzyme
 Bile salts help in combination of lipase with two molecules of a small
protein called as Colipase. This combination enhances the lipase
activity.
 Bile salts also help in the emulsification of fats
TG particle
Colipase

lipase
 Emulsification by Bile Salts

Bile salts as emulsifying agents interact with the dietary lipid particles and
the aqueous duodenal contents, thereby stabilizing the lipid particles as
they become smaller, and preventing them from coalescing.
Emulsification and Digestion
of Triglycerides
Absorption of Lipids
 Free fatty acids, free cholesterol and 2- mono-acylglycerols are the
primary products of lipid digestion.
 Glycerol, short and medium chain fatty acids (Chain length less than
14 carbons) are directly absorbed from the intestinal lumen in to the
portal vein and taken to liver for further utilization.
 Long chain fatty acids, free cholesterol, fat soluble vitamins (A, D, E,
and K) together with bile salts form mixed micelles.
 Micelles are disk shaped clusters of amphipathic lipids that coalesce
with their hydrophobic groups on the inside and their hydrophilic
groups on the outside of clusters.
 Mixed micelles are soluble in the aqueous environment of the
intestinal lumen
 The micelles approach the brush border membrane of the enterocytes
 Micelles
 Hydrophilic surface of
micelles facilitates the
transport of the hydrophobic
lipids
The drug ezetimibe blocks a
protein that specif ically mediates
cholesterol transport across the
plasma membrane of
enterocytes.
Ezetimibe has been shown to
be effective at reducing levels of
LDL cholesterol, par ticularly
when combined with a statin, a
drug that inhibits cholesterol
synthesis in the liver.
Lipid Malabsorption(Steatorrhea)
 Lipid malabsorption results in increased
lipids including fat soluble vitamins A,D E
and K in the feces.
 Cause may be pancreatic insuf ficiency,
i n c l u d i n g c y s t i c f ib ro s i s , c h ro n i c
diseases of pancreas or surgical removal
of pancreas
 Shortened bowel, Celiac diseases, sprue
or crohn’s disease
 May be bile duct obstruction due to gall
stones, tumor of head of pancreas,
enlarged lymph nodes etc.
 Milk a nd coconut oil a re used
thera peutica lly since they conta in
medium chain fatty acids.
Summary of lipid digestion and
Absorption

Chylomicrons deliver absorbed TAG to the body's

cells. TAG in chylomicrons and other lipoproteins are
hydrolyzed by lipoprotein lipase, an enzyme that is
found in capillary endothelial cells. Monoglycerides
and fatty acids released from digestion of TAG then
diffuse into cells.