2. What are lipids?
•The lipids constitute a very important heterogenous group of
organic substances in plant and animal tissues, and related
either actually or potentially to the fatty acids.
•Chemically they are various types of esters of different alcohols.
• In addition to alcohol and fatty acids, some of the lipids may
contain phosphoric acid, nitrogenous base and carbohydrates.
3. Bloor’s Criteria of lipids
According to Bloor, lipids are compounds having the following
characteristics:
1. They are insoluble in water.
2. Solubility in one or more organic solvents, such as ether,
chloroform, benzene, acetone, etc, so called fat solvents.
3. Some relationship to the fatty acids as esters either actual or
potential.
4. Possibility of utilization by living organisms.
Thus, lipids include fats, oils, waxes and related compounds.
An oil is a lipid which is liquid at ordinary temperature.
Distinction between fats and oils is a purely physical one.
Chemically they are all esters of glycerol with higher fatty acids.
4. Biomedical Importance of
lipids
1. Lipids are important dietary constituent and acts as fuel in
the body.
2. In some aspects lipid is even superior to carbohydrates as a
raw material for combustion, since it yields more energy per
gm (9.5 Cal/gm as compared to carbohydrates 4.0 Cal/gm).
3. Can be stored in the body in almost unlimited amount in
contrast to carbohydrates.
4. Some deposits of lipids may exert an insulating effect in the
body, while lipids around internal organs like kidney, etc.
may provide padding and protect the organs.
5. Building materials: Breakdown products of fats can be
utilized for building biological active materials.
5. 6. Lipids supply so called Essential fatty acids (EFA), which
cannot be synthesized in the body and are essential in the diet
for normal health and growth.
7. The nervous system is particularly rich in lipids especially
certain types and are essential for proper functioning.
8. Some vitamins like, A, D, E and K are fat soluble, hence lipid is
necessary for these vitamins.
9. Lipoproteins and phospholipids are important constituents of
many natural membranes such as cell walls and cell organelles
like mitochondrion, etc.
10. Lipoproteins are also ‘carriers’ of triglycerides, cholesterol
and PL in the body
7. 1. Simple lipids
Esters of fatty acids with various alcohols:
(a) Neutral fats (Triacylglycerol, TG):
These are tri-esters of fatty acids with glycerol.
(b) Waxes are esters of fatty acids with higher monohydroxy
aliphatic alcohols.
• True waxes are esters of higher fatty acids with cetyl alcohol
(C16H33OH) or other higher straight chain alcohols.
• Cholesterol esters are esters of fatty acid with cholesterol.
• Vit A and Vit D esters are palmitic or stearic acids esters of Vit
A (Retinol) or Vit D respectively
8. Triacylglycerol (TG)
Neutral fats (TG) are all tri-esters
of the trihydric alcohol, glycerol
with various fatty acids.
The type formula for a neutral fat
(TG) is given in which R1 R2 R3
represent fatty acid chains which
may or may not all be the same.
Naturally occurring fats have
apparently the D-structural
configuration
9. Physical Properties
1. Neutral fats are colorless, odorless and tasteless substances.
The color and taste of some of the naturally occurring fats is due to
extraneous substances.
2. Solubility:
They are insoluble in water but soluble in organic fat solvents.
3. Specific gravity:
The specific gravity of all fats is less than 1.0, consequently all fats
float in water.
4. Emulsification: Emulsions of fat may be made by shaking vigorously
in water and by emulsifying agents such as gums, soaps and proteins
which produce more stable emulsions.
5. Melting point and consistency:
The hardness or consistency of fats is related to their MP. Glycerides
of lower FA melt at lower temperature than those of the higher fatty
acids, and the unsaturated fatty acids glycerides at still lower
temperature
10. Chemical Properties of TG
1. Hydrolysis:
Lipases are enzymes which hydrolyze a triglyceride
yielding fatty acids and glycerol.
Sites: Lipases are found in human body in following
places.
(a) Lingual lipase in saliva,
(b) Gastric lipase in gastric juice,
(c) Pancreatic lipase in pancreatic juice,
(d) Intestinal lipase in intestinal epithelial cell,
(e) Adipocytic lipase in adipose tissue, and
(f) Serum lipase.
Pancreatic lipase is peculiar in that it can hydrolyze
ester bonds in positions 1 and 3 preferentially, than
in position 2 of TG molecule
11.
12. 2. Saponification:
Hydrolysis of a fat by an alkali is called saponification.
The resultant products are glycerol and the alkali salts of the fatty
acids, which are called “soaps”.
Soaps are cleansing agents because of their emulsifying action.
Some soaps of high molecular weight and a considerable degree
of unsaturation are selective germicides, others such as Na-
ricinoleate, have detoxifying activity against diphtheria and
tetanus toxins.
13. 3. Additive Reactions
The unsaturated fatty acids present in neutral fat exhibits all the
additive reactions, i.e. hydrogenation, halogenation, etc.
Oils which are liquid at ordinary room temperature, on
hydrogenation become solidified.
This is the basis of vanaspati (Dalda) manufacture, where
inedible and cheap oils like cotton seed oil are hydrogenated
and converted to edible solid fat.
14. 4. Oxidation
Fats very rich in unsaturated fatty acids such as linseed oil
undergo spontaneous oxidation at the double bond forming
aldehydes, ketones and resins which form transparent coating on
the surfaces to which the oil is applied.
These are called drying oils and are used in the manufacture of
paints and varnishes.
5. Rancidity
The unpleasant odor and taste developed by most natural fats on
aging is referred to as rancidity.
15. Cause of rancidity:
Rancidity may be caused by the following:
• Hydrolysis of fat yields free fatty acids and glycerol and/or mono
and diglycerides. Process is enhanced by presence of lipolytic
enzymes lipases, which in the presence of moisture and warm
temperature bring about hydrolysis rapidly.
• By various oxidative processes, oxidation of double bonds of
unsaturated glycerides may form “peroxides”, which then
decompose to form aldehydes of objectionable odor and taste.
The process is greatly enhanced by exposure to light.
Prevention of rancidity:
Vegetable fats contain certain substances like vitamin E, phenols,
hydroquinones, tannins and others which are antioxidants and
prevents development of rancidity. Hence vegetable fats preserve
for longer periods than animal fats
16. 2. Compound/Complex Lipids
Esters of fatty acids containing groups, other than, and in
addition, to an alcohol and fatty acids.
(a) Phospholipids:
They are substituted fats containing in addition to fatty acid and
glycerol, a phosphoric acid residue, a nitrogenous base and other
substituents.
Examples: phosphatidyl choline (Lecithin), phosphatidyl
ethanolamine (Cephalin), phosphatidyl inositols (Lipositols),
phosphatidyl serine, plasmalogens, sphingomyelins, etc.
17. (b) Glycolipids:
Lipids containing carbohydrate moiety are called glycolipids.
They contain a special alcohol called sphingosine or sphingol
and nitrogenous base in addition to fatty acids but does not
contain phosphoric acid or glycerol.
These are of two types:
• Cerebrosides
• Gangliosides
(c) Sulpholipids:
Lipids characterised by possessing sulphate groups.
(d) Aminolipids (Proteolipids)
(e) Lipoproteins: Lipids as prosthetic group to proteins.
18. 3. Derived Lipids
Derivatives obtained by hydrolysis of those given in group I and II,
which still possess the general characteristics of lipids.
(a) Fatty acids may be saturated, unsaturated or cyclic.
(b) Monoglycerides (Monoacylglycerol) and Diglycerides
(Diacylglycerol).
(c) Alcohols
• Straight chain alcohols are water insoluble alcohols of higher
molecular weight obtained on hydrolysis of waxes.
• Cholesterol and other steroids including Vit D.
• Alcohols containing the β-ionone ring include Vit A and certain
carotenoids.
• Glycerol.
19. 4. Miscellaneous
Aliphatic hydrocarbons include iso-octadecane found in liver fat
and certain hydrocarbons found in bees wax and plant waxes.
• Carotenoids
• Squalene is a hydrocarbon found in shark and mammalian
liver and in human sebum.
• Vitamins E and K.
20. Chemistry of Fatty acids
Fatty acids consist of a hydrophobic hydrocarbon chain with a
terminal carboxyl group which ionizes at physiological pH and
becomes COO-
Fatty acids are amphipathic in nature ( Have both hydrophobic and
hydrophilic regions)
In Long chain Fatty acids hydrophobic region is dominant and they
are water insoluble, their transportation needs protein
21. Fatty acids may be present in plasma in two forms
Ester form: (90% occur as esters) e.g. triacylglycerol, cholesteryl
esters and phospholipids. These are present in natural fats and
oils.
Free form: They are transported in association with albumin.
They can be oxidized by many tissues particularly liver and
muscles to provide energy.
22. Nomenclature of Fatty acids
Saturated Fatty acids ends in anoic acid
Unsaturatd Fatty acids ends in enoic acid
Carboxyl carbon is numbered 1
Carbons numbers 2,3,4 are called α,β,γ while terminal carbon is
called ω
Various conventions use Δ for indicating the number and
position of the double bonds; e.g,
• Δ9 indicates a double bond between carbons 9 and 10 of the
fatty acid;
• ω9 indicates a double bond on the ninth carbon counting from
the ω- carbon.
• In animals, additional double bonds are introduced only
between the existing double bond (e.g, ω9, ω6, or ω3) and the
carboxyl carbon, leading to three series of fatty acids known as
the ω9, ω6, and ω3 families, respectively.
23. Classification of fatty acids
Saturated Fatty Acids:
These are without Double Bonds and include Lauric acid
(C12), Myristic acid (C14), Palmitic acid (C16), Stearic acid
(C18).
Unsaturated Fatty Acids:
These Fatty acids contain double bonds and are classified
on the basis of number of double bonds.
Monounsaturated F.A.
They contain one double bond and are called monenoic, e.g.
Palmitoleic acid and oleic acid.
Polyunsaturated F.A.
They have two or more than two double bonds
and are called polyenoic, e.g. Linoleic, linolenic
acid and arachidonic acid.
24. Essential Fatty Acids
The Fatty acids which are not synthesized in our body and their
dietry intake is essential are called essential Fatty acids.
Two Fatty acids are essential.
1. Linoleic Acid: which is the precursor of ω-6 arachidonic acid,
the substrate for prostaglandin synthesis
2. α-linolenic acid: the precursor of other ω-3 fatty acids
important for growth and development.
• Plants provide us with the essential fatty acids.
• Deficiency of Essential Fatty acids cause Scaly dermatitis
(Ichthyosis), visual and neurological abnormalities.
• Arachidonic acid (Semi essential fatty acid) becomes essential
if linoleic acid is deficient in the diet.
25. Classification on the basis of
carbon chain length
Short chain fatty acids
They include fatty acids with 2-4 carbon atoms
Medium chain fatty acids
They include fatty acids with 6-10 carbon atoms
Long chain fatty acids
They include fatty acids with 12-26 carbon atoms
26. Complex lipids
1. Glycerophospholipids when alcohol is glycerol
2. Sphingo-phospholipids when alcohol is sphingosine
These are structural component of membranes and play role in
generation of lipid signaling molecules
27. 1. Glycerophospholipids
These are major class of phospholipids
They contain glycerol as alcohol component
All the members of this group are derived from phosphatadic acid (A
diacylglycerol with phosphate at 3rd carbon)
They are different depending upon the presence of different groups
as
1. phsophotidylserine contain serine group
2.Phosphatidylethanolamine (Cephalins) contain ethanolamine group
3. Phoshpatidylcholine (Lecithins) contain choline group
4. Phoshpotidylinositol (PI) contain inositol group
5. Phosphatidylglycerol contain glycerol group
28.
29. Other types of Glycerophospholipids
These include following,
1. Cardiolipin (Diphosphotidylglycerol)
2. Plasmalogens with ether linkage
3. Platelet Activating Factor (PAF)
30. 1. Cardiolipin (Diphosphatidylglycerol)
Two molecules of Phosphatadic Acid are esterified
through their phosphate groups to an additional
molecule of glycerol is called cardiolipin
(diphosphatidylglycerol).
It is found in bacteria and eukaryotes.
In eukaryotes, cardiolipin is virtually exclusive to the
inner mitochondrial membrane, where it appears to
be required for the maintenance of certain
respiratory complexes of the electron transport
chain.
It also have antigenic properties and is recognized by
antibodies
31. 2. Plasmalogen
When the fatty acid at carbon 1 of a
glycerophospholipid is replaced by an
unsaturated alkyl group attached by an ether
(rather than by an ester) linkage to the core
glycerol molecule, a plasmalogen is produced.
For example, phosphatidalethanolamine
(abundant in nerve tissue) is the plasmalogen
that is similar in structure to
phosphatidylethanolamine.
Phosphatidalcholine (abundant in heart
muscle) is the other quantitatively significant
ether lipid in mammals.
32. 3. Platelet Activating Factor
(PAF)
This is an unusual ether glycerophospholipid with
1. a saturated alkyl group in an ether link to carbon1
2. an acetyl residue (rather than a fatty acid) at carbon 2of the
glycerol backbone
33. PAF is synthesized and released by a variety of cell types.
It binds to surface receptors, triggering potent thrombotic and
acute inflammatory events.
For example, PAF activates inflammatory cells and mediates
hypersensitivity, acute inflammatory, and anaphylactic
reactions.
It causes platelets to aggregate and degranulate, and
neutrophils and alveolar macrophages to generate superoxide
radicals.
34. 2. Sphingophospholipids
Sphingomyelin:
The backbone of sphingomyelin is the
amino alcohol sphingosine, rather than
glycerol
A long-chain fatty acid is attached to the
amino group of sphingosine through an
amide linkage, producing a ceramide, which
can also serve as a precursor of glycolipids.
The alcohol group at carbon 1 of
sphingosine is esterified to
phosphorylcholine, producing
sphingomyelin, the only significant
phospholipid in humans
35. Sphingomyelin is an important constituent of the myelin of
nerve fibers.
[Note: The myelin sheath is a layered, membranous structure
that insulates and protects neuronal fibers of the central
nervous system.]
36. Glycolipids
Glycolipids are molecules which contain both carbohydrates and
lipid components.
Like sphingomyelin, glycolipids are also derivatives of ceramides
in which a long-chain fatty acid is attached to the amino alcohol
sphingosine. They are, therefore, more precisely called
glycosphingolipids.
[Note: Ceramides, then, are the precursors of both
phosphorylated and glycosylated sphingolipids.]
Like the phospholipids, glycosphingolipids are essential
components of all membranes in the body, but they are found in
greatest amounts in nerve tissue.
They are located in the outer leaflet of the plasma membrane,
where they interact with the extracellular environment.
As such, they play a role in the regulation of cellular interactions,
growth, and development.
37. Glycosphingo lipids are antigenic, and they have been
identified as a source of blood group antigens, various
embryonic antigens specific for particular stages of fetal
development, and some tumor antigens.
[Note: The carbohydrate portion of a glycolipid is the
antigenic determinant.]
They also serve as cell surface receptors for cholera and
tetanus toxins, as well as for certain viruses and microbes.
Genetic disorders associated with an inability to properly
degrade the glycosphingolipids result in lysosomal
accumulation of these compounds.
38. Structure of glycolipids
The glycosphingolipids differ from sphingomyelin in that they do
not contain phosphate, and the polar head function is provided by
a monosaccharide or oligosaccharide attached directly to the
ceramide by an O-glycosidic bond.
The number and type of carbohydrate moieties present help
determine the type of glycosphingolipid
Depending on the presence of carbohydrate moiety present, it is
of two types
1. Neutral glycosphingolipids (Cerebrosides)
2. Acidic glycosphingolipids
Gangliosides & Sulfatides
39. Neutral Glycosphingolipids
(Cerebrosides)
These are ceramide monosaccharides that contain either
a molecule of
Galactose (galactocerebroside (the most common
cerebroside found in membranes)
Glucose (gluco cerebroside, which serves primarily as an
intermediate in the synthesis and degradation of the
more complex glycosphingolipids).
[Note: Members of a group of galactocerebrosides (or
glucocerebrosides) may also differ from each other in the
type of fatty acid attached to the sphingosine.]
cerebrosides are found predominantly in the brain and
peripheral nervous tissue, with high concentrations in the
myelin sheath.
40. Acidic glycosphingolipids
Acidic glycosphingolipids are negatively
charged at physiologic pH.
The negative charge is provided by N-
acetylneuraminic acid (NANA, a sialic acid)
in gangliosides, or by sulfate groups in
sulfatides.
42. Cholesterol
Cholesterol is a very hydrophobic compound.
It consists of four fused hydrocarbon rings (A-
D) called the “steroid nucleus”), and it has an
eight-carbon, branched hydrocarbon chain
attached to carbon 17 of the D ring.
Ring A has a hydroxyl group at carbon 3, and
ring B has a double bond between carbon 5
and carbon 6
43. Sterols
Steroids with eight to ten carbon atoms in the side chain at carbon 17 and
a hydroxyl group at carbon 3 are classified as sterols
Cholesterol is the major sterol in animal tissues. [Note: Plant sterols, such
as β-sitosterol are poorly absorbed by humans.
After entering the enterocytes, they are actively transported back into
the intestinal lumen.
Because some cholesterol is transported as well, plant sterols appear to
reduce the absorption of dietary cholesterol.
This has led to clinically useful dietary treatment of hypercholesteremia.
Daily ingestion of plant steroid esters (in the form of commercially
available trans fatty acid–free margarine) is one of a number of dietary
strategies leading to the reduction of plasma cholesterol levels.
44. Cholesterol esters
Most plasma cholesterol is in an esterified form (with a fatty
acid attached at carbon 3, which makes the structure even
more hydrophobic than free (unesterified) cholesterol.
Cholesteryl esters are not found in membranes, and are
normally present only in low levels in most cells.
Because of their hydrophobicity, cholesterol and its esters must
be transported in association with protein as a component of a
lipoprotein particle Or be solubilized by phospholipids and bile
salts in the bile.
45. Functions of cholesterol
1. Hormone production. Cholesterol plays a part in producing
hormones such as estrogen, testosterone, progesterone, aldosterone
and cortisone.
2. Vitamin D production. Vitamin D is produced when the sun’s
ultraviolet rays reach the human skin surface.
3. Bile production. Cholesterol produces bile acids which aid in
digestion and vitamin absorption.
4. Cell membrane support. Cholesterol plays a very important part in
both the creation and maintenance of human cell membrane.
46. Bile
Bile consists of a watery mixture of organic and inorganic
compounds.
Phosphatidylcholine (lecithin) and bile salts (conjugated bile
acids) are quantitatively the most important organic
components of bile.
Bile can either pass directly from the liver where it is
synthesized into the duodenum through the common bile
duct, or be stored in the gallbladder when not immediately
needed for digestion.
47. Structure of the bile acids
The bile acids contain 24 carbons, with two or three hydroxyl
groups and a side chain that terminates in a carboxyl group.
The carboxyl group has a pKa of about six and, therefore, is not
fully ionized at physiologic pH, the term “bile acid.”
48.
49. The bile acids are amphipathic in that the hydroxyl groups are
α in orientation (they lie “below” the plane of the rings) methyl
groups are β (they lie “above” the plane of the rings)
Therefore, the molecules have both a polar and a non-polar
face can act as emulsifying agents in the intestine, helping
prepare dietary triacylglycerol and other complex lipids for
degradation by pancreatic digestive enzymes.
50. Synthesis of bile acids
Bile acids are synthesized in the liver by a multistep, multi-organelle
pathway in which
1. hydroxyl groups are inserted at specific positions on the steroid
structure,
2. the double bond of the cholesterol B ring is reduced
3. the hydrocarbon chain is shortened by three carbons, introducing a
carboxyl group at the end of the chain.
The most common resulting compounds, cholic acid (a triol) and cheno
- deoxycholic acid (a diol) are called “primary” bile acids.
51. The rate-limiting step in bile acid
synthesis is the introduction of a
hydroxyl group at carbon 7 of the steroid
nucleus by cholesterol-7-α-hydroxylase,
an ER-associated cytochrome P450 (CYP)
enzyme found only in liver.
The enzyme is down-regulated by cholic
acid
52. Bile salts
Before the bile acids leave the liver, they are conjugated to a
molecule of either glycine or taurine (an endproduct of cysteine
metabolism) by an amide bond between the carboxyl group of
the bile acid and the amino group of the added compound.
These new structures include
glycocholic and glyco cheno deoxycholic acids,
taurocholic and tauro cheno deoxy cholic acids
The ratio of glycine to taurine forms in the bile is approximately
3:1.
53. Bile salts are more effective detergents than bile acids because of
their enhanced amphipathic nature.
Therefore, only the conjugated forms—that is, the bile salts are
found in the bile.
Individuals with genetic deficiencies in the conversion of
cholesterol to bile acids are treated with exogenously supplied
cheno deoxycholic acid.
Bacteria in the intestine can remove glycine and taurine from bile
salts, regenerating bile acids.
54. Between 15 and 30 g of bile salts are secreted from the liver
into the duodenum each day
about 0.5 g (less than 3%) is lost daily in the feces.
Approximately 0.5 g/day is synthesized from cholesterol in the
liver to replace the lost bile acids
55. Bile Salt deficiency:
cholelithiasis
The movement of cholesterol from the liver into the bile
must be accompanied by the simultaneous secretion of
phospholipid and bile salts.
If this dual process is disrupted and more cholesterol
enters the bile than can be solubilized by the bile salts
and phosphatidylcholine present, the cholesterol may
precipitate in the gallbladder, leading to cholesterol
gallstone disease, cholelithiasis.
