It will helpful for your reference

1. Properties of Fatty Acids

2. Physical Properties:
1. State. Fats containing saturated fatty acids are solid at ordinary room
temperature. The animal fats belong to this
category. Most plant fats, on the contrary, possess unsaturated fatty acids and are,
henceforth, liquid at room temperature.
2. Colour, Odour and Taste. When pure, the fats arecolourless, virtually odourless
and possess an extremely bland taste.
• They are capable of absorbing a variety of odours and hence flavour during
storage.
• The perfumes of some flowers can be isolated by placing their petals in contact
with the fat for a certain period, then extracting the fat with alcohol and
concentrating the essence.

3. 3. Solubility.
• The fats are only sparingly soluble in water. Therefore, described as hydrophobic
in contrast to the water-soluble or hydrophilic substances like many
carbohydrates and proteins.
• These are freely soluble in organic solvents like chloroform, ether, acetone and
benzene.
• These solvents, as they dissolve fats are also known as ‘fat solvents’.
• The solubility of the fatty acids in organic solvents decreases with the increase
of chain length.
• The introduction of hydroxyl groups, increases solubility.

4. 4. Melting point.
• The melting point of fats depends on the chain length of the constituent fatty
acid and the degree of unsaturation.
• Fats containing saturated fatty acids from C 4 to C 8 are liquid at room
temperature but those containing C 10 or higher saturated fatty acids are solid
and their melting points increase with increasing chain length.
• With the introduction of double bond in the fat molecule, the melting point
lowers considerably.
• It is described that greater the degree of unsaturation (or higher the number of
double bonds) of the constituent fatty acid, the lower is the melting point of the
fat.

5. Short chain length and
unsaturation enhance the
fluidity of fatty acids and
of their derivatives.

6. 5. Specific gravity.
• The specific gravity of the fats is less than 1 (about 0.86). they float on water
surface. Solid fats are lighter than the liquid fats.
• Oils spread on water to form thin monomolecular layers.
• In general, either unsaturation of the fatty acid chains increase or increase in chain
length of the fatty acid residues tend to increase the specific gravity.
6. Geometric isomerism. As stated earlier, the presence of double bond (s) in the
unsaturated fatty acid part of the fat molecule produces geometric (or cis-trans)
isomerism.

7. 7. Insulation.
• The fats possess high insulating power, i.e., they are bad conductor of heat.
• A layer of fat below the skin provides a sort of blanket for warm-blooded animals
(or homoiotherms).This is especially important for whales and seals which have
to maintain a high temperature in cold waters.
• The fishes are cold-blooded animals (or poikilotherms) and do not require
maintenance of high temperature and so have very little subcutaneous fat.
8. Emulsification.
• The process, where lipid mass is converted into a number of small lipid droplets.
• The fats may be emulsified by shaking either with water or with emulsifying
agents like soaps, gums, proteins etc. An emulsifying agent produces a finely
divided suspension of a fat in an aqueous medium.
• The hydrocarbon portions of the two (the emulsifier and the fat) tend to aggregate.
This leaves the water-soluble group of the emulsifier projecting into the aqueous
phase.

8. • A fat droplet will associate with a number of molecules of the emulsifier, thus
producing a new watersoluble surface.
• Water molecules, tend to be held in a layer or ‘cloud’ around each droplet, thus
disallowing the aggregation of the fat droplets.
• The process of emulsification is of great metabolic significance.
• The fats have to be emulsified before they can be absorbed by the intestinal
wall. The process is accomplished by the bile juice secreted from liver.
9. Surface tension.
• The force with which the surface molecules are held
together is called the surface tension.
• When liquid fat is poured on water, it spreads uniformly
over the surface of water in the form of a unimolecular
layer and thus reduces the surface tension of water.

9. Chemical Properties:
1. Hydrolysis.
Fats undergo hydrolysis when treated with mineral acids, the alkalies or fat
splitting enzyme lipase or hydrolases to yield glycerol and the constituent
fatty acids.
Hydrolysis by alkalies, such as NaOH or KOH leads to the formation of
sodium or potassium salts of fatty acids. The salts are known as soaps and
process of its formation is saponification.

11. 2. Saponification.
• The hydrolysis of fats by alkali is called saponification. This reaction results in
the formation of glycerol and salts of fatty acids which are called soaps.
• The soaps are of two types : hard and soft.
• Hard soaps such as the common bar soaps are the sodium salts of the higher fatty
acids.
• Soft soaps are the potassium salts of higher fatty acids and are marketed as
semisolids or pastes.
• The fatty acid salts of calcium, magnesium, zinc and lead are, however, insoluble
in water.
Soaps consist of fatty acids

12. 3. Hydrolytic rancidity.
• When butter or other fats are stored, they often become rancid and hence
unpalatable.
• Rancidity is caused by the growth of microorganisms which secrete enzymes
like lipases.
• These split the fats into glycerol and free fatty acids.
• The fatty acids impart unpleasant odour and flavour to the fat.
• However, butter may be prevented from becoming rancid by refrigeration or by
exclusion of water.

13. REACTIONS INVOLVING DOUBLE BOND
1. Hydrogenation.
• Unsaturated fatty acids, either free or combined in lipids, react with gaseous
hydrogen to yield the saturated fatty acids, catalyzed by platinum, palladium or
nickel.
• The addition of hydrogen takes place at the C—C double bond (s).
• 1 mole of oleic, linoleic or linolenic acid reacts with 1, 2 or 3 moles of hydrogen
respectively to form stearic acid.
• the transformation of unsaturated liquid vegetable fats into solid fats.
• Used in the manufacture of candles, vegetable shortenings and of oleomargarine.

14. 2. Halogenation.
Unsaturated fatty acids and their esters can take up halogens like Br2 and I2 at
their double bond (s) at room temperature in acetic acid or methanol solution.
(‘iodine number determination)

15. 3. Oxidation.
Unsaturated fatty acids are susceptible to oxidation at their double bonds.
Oxidation may be carried with ozone or KMnO4.
• (a) With ozone – An unstable ozonide is formed which later cleaves by water to
give rise to 2 aldehydic groups.

16. • With KMnO4 – Under mild conditions, the glycols are formed at the sites
of double bonds.
• Under vigorous conditions, the same reagent cleaves the molecule at the
double bond and oxidizes the terminal portions to the carboxyl group.

17. 4. Oxidative rancidity
• Oils containing highly unsaturated fatty acids are spontaneously oxidized by
atmospheric oxygen at ordinary temperatures.
• The oxidation takes place slowly and results in the formation of short chain fatty
acids (C4 to C10) and aldehydes which give a rancid taste and odour to the fats.
• This is ‘oxidative rancidity’ and is due to a reaction called `autoxidation'.

18. • Oxidative rancidity is observed more frequently in animal fats than in vegetable
fats.
• The presence of natural ‘antioxidants’ such as tocopherols (= vitamin E), phenols,
naphthols etc. in the vegetable oils.
• Synthetic antioxidants such as nordihydroguiaretic acid (NDGA), tertiary butyl
hydroxy anisole (BHA) etc.
• Linseed oil, used for paints, rich in unsaturated fatty acids. It undergoes
autoxidation in air, polymerized to hard, resinous coating as it ‘dries’ or oxidizes.
• The action of antioxidants is opposed by a group of compounds present in the fats
and oils. They oxidise the parent compound and are called pro-oxidants.
• Pro-oxidants are formed during the processing and refining of fats.
e.g. copper, iron and nickel salts of organic acids like lactic

19. Reaction involving OH groups
Dehydration (Acrolein test):
• Fats are heated in the presence of a dehydrating agent, NaHSO4 or KHSO4
produce an unsaturated aldehyde called acrolein from the glycerol moiety.
• Acrolein is recognized by its pungent odour
• test to detect the presence of glycerol in fat molecule.

20. Saponification value, Iodine value, peroxide
value, acid value, and their significance

21. Saponification
• The hydrolysis of fats by alkali is called saponification.
• This reaction results in the formation of glycerol and salts of fatty acids which
are called soaps
• The soaps are of two types : hard and soft.
• Hard soaps such as the common bar soaps are the sodium salts of the higher fatty
acids.
• Soft soaps are the potassium salts of higher fatty acids
Saponification number
• The number of milligrams of KOH required to saponify 1 gm of fat.
• Provides information of the average chain length of the fatty acids in the fat.
• It varies inversely with the chain length of the fatty acids - shorter the average
chain length of the fatty acids, the higher is the saponification number.

22. Iodine value (or Koettstorfer number)
• The number of grams of iodine absorbed per 100g of fat.
• A measure of the degree of unsaturation of the fatty acids in the fat.
• Oils like soybean, corn and cottonseed have higher iodine numbers 133, 127 and
109, respectively (possess more unsaturated fatty acids)
• The solid fats such as beef fat or tallow (42).
• The iodine number gives no indication as to the number of double bonds present
in the fatty acid molecule.

23. Peroxide value (POV)
• The reactive oxygen contents expressed in terms of milliequivalents (meq) of
free iodine per kilogram of fat.
• It is determined by titrating iodine liberated from potassium iodide(KI)
with sodium thiosulphate solution.
• The POV of Fresh Oils is below 10 meq/kg.
Acid value.
• The number of milligrams of KOH required to neutralize the free fatty acids
present in 1 gm of fat.
• This gives us the quantity of free fatty acid present in a fat.
• A fat, both processed and stored properly, has a very low acid number.

24. Polenske number
• The number of millilitres of 0.1N KOH required to neutralize the insoluble fatty
acids obtained from 5 gm of fat by steam distillation.
• These are not volatile and obtained by steam distillation
Reichert-Meissl number
• The number of millilitres of 0.1N KOH required to neutralize the soluble, volatile
fatty acids derived from 5 g of fat.
• It measures the quantity of short chain fatty acids (up to C 10 inclusive) in the fat
molecule.
• The Reichert-Meissl numbers of coconut and palm oils range between 5 and 8.
Butterfat is exceptional in having a high Reichert-Meissl number, ranging from 17
to 35.
• Helps in the detection of foreign fats in adulterated butter.

25. Acetyl number
• The number of milligrams of KOH required to neutralize the acetic acid obtained
by saponification of 1 gm of fat after it has been acetylated.
• The treatment of fat or fatty acid mixture with acetic anhydride results in
acetylation of all alcoholic OH groups.
• A measure of the number of OH groups in the fat.
For example: the castor oil has a high acetyl number (146) because of high
content of a hydroxy acid, ricinoleic acid, in it.

26. Analytical values for some fats and oils

27. Fatty acid composition of some common fats and oils (in g/100g)

28. Phosphoglycerides: structure and roles

29. Glycerophospholipids
• Phospholipids that contain glycerol are called glycerophospholipids (or
phosphoglycerides).
• Glycerophospholipids constitute the major class of phospholipids.
• All contain/are derivatives of phosphatidic acid (diacyl glycerol with a
phosphate group on the third carbon).
• Phosphatidic acid is the simplest phosphoglyceride, and is the precursor of the
other members of this group.
29

30. • Glycerophospholipids are formed from phosphatidic acid and alcohol
The phosphate group on phosphatidic acid (PA) can be esterified to another
compound containing an alcohol group.
For example:
Serine + PA phosphatidylserine
Ethanolamine + PA phosphatidylethanolamine (cephalin)
Choline + PA phosphatidylcholine (lecithin)
Inositol + PA phosphatidylinositol
Glycerol + PA phosphatidylglycerol
30

31. Glycerophospholipids
• Glycerol is the alcohol
• Two acids are Fatty Acids
• Third is esterified to PO4
3- and choline
• The Fatty Acid on carbon 2 is unsaturated
31
choline
CH2 CH2OH
N
H3C
CH3
CH3
+
glycerol
H2C
HC
H2C
OH
OH
OH

32. 32

33. Cardiolipin:
• Two molecules of phosphatidic acid esterified through their phosphate groups
to an additional molecule of glycerol are called cardiolipin (diphosphatidyl
glycerol.
• This the only human glycerophospholipid that is antigenic.
For example,
Cardiolipin is recognized by antibodies raised against
Treponema palladium , the bacterium that
causes syphylis.
[Cardiolipin is an important
component of the inner mitochondrial
membrane and bacterial membranes.]
33

34. Plasmalogens:
• The fatty acid at carbon 1 of a glycerol phospholipid is replaced by an
unsaturated alkyl group attached by an ether (rather than by an ester) linkage
to the core glycerol molecule, to give plasmalogen.
For example: phosphatidal ethanolamine (abundant in nerve tissue, is the
plasmalogen that is
similar in structure to phosphatidyl ethanolamine.
Phosphatidal choline (abundant in heart muscle)
is the other quantitatively
significant ether lipid in mammals.
34

35. PHOSPHATIDYLINOSITOL [PtdIns{4,5}P2 ]
• PI IS Aubiquitous membrane lipid in eukaryotes It is becoming
increasingly obvious that Piand its metabolites play a myriad of very
diverse roles in eukaryotic cells The saccharomyces cerevisiae PIS1
gene is essential and encodes PI synthase ‘which is required for the
synthesis of PI
• IMPORTANCE IN BODY;-
• The establishment of organelle identity ‘the regulation of
cytoskeleton and membrane dynamics

36. Lecithins are composed of phosphoric acid, cholines, esters
of glycerol, and two fatty acids; the chain length, position,
and degree of unsaturation of these fatty acids vary, and this
variation results in different lecithins with different biological
functions.
LECITHINS
reduces plasma membrane disruption by hydrophobic bile salts. This
protection may be attributable to association of bile salts with vesicles and
mixed micelles, reducing the concentration of bile salt monomers and simple
micelles available to interact with cell membranes.

37. CEPHALIN [phosphatidylethanolamine-PE ]
Cephalin is a phospholipid with the polar ethanolamine found in
phosphoester linkage to diacylglycerol. Derivatives of phosphatidic
acids in which the phosphoric acid is bound in ester linkage to an
ethanolamine moiety
Cephalins are found in most cell membranes,
particularly in brain tissues.

38. Platelet activating factor(PAF)
• An unusual ether glycerophospholipid, with a saturated alkyl group in an
ether link to carbon1 and an acetyl residue (rather than a fatty acid) at carbon2
of the Glycerol backbone.
• PAF is synthesized and released by a variety of cell types. 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.
38

39. 39
It causes platelets to aggregate and degranulate, and neutrophils and alveolar
macrophages to generate superoxide radicals.
PAF is one of the most potent bioactive molecules known, causing effects at
concentrations as low as 10-12mol/L].

40. a. Significance of choline reutilization:
The reutilization of choline is important because, whereas humans can
synthesize choline de novo the amount made is insufficient for our needs.
Thus, choline is an essential dietary nutrient with an adequate Intake (550
mg for men and 420 mg for women).
40

41. Role of PC in lung surfactant:
Dipalmitoyl-Phosphatidyl choline (DPPC, or dipalmitoylecithin). Positions 1
and 2 on the glycerol are occupied by palmitate DPPC, made and secreted by
granular pneumocytes.
It is the major lipid component of lung surfactant—the extracellular fluid layer
lining the alveoli. Surfactant serves to decrease the surface tension of this fluid
layer, reducing the pressure needed to rein late alveoli, thereby preventing
alveolar collapse (atelectasis).
Respiratory distress syndrome (RDS) in preterm infants is associated with
insufficient surfactant production, and is a significant cause of all neonatal
deaths in western countries.
41

42. Role of PI in signal transmission across membranes:
The phosphorylation of membrane bound phosphatidyl inositol produces
polyphospho-inositides,
e.g. 4,5-bisphosphate.
The degradation of PIP2 by phospholipase C occurs in response to the binding
of a variety of neurotransmitters, hormones, and growth factors to receptors on
the cell membrane.
The products of this degradation, inositol 1,4,5 trisphosphate (IP3) and
diacylglycerol (DAG), mediate the mobilization of intracellular calcium and
the activation of protein kinase C, respectively, which act synergistically to
evoke specific cellular responses.
Transmission across the membranes thus accomplished.
42

43. Role of PI in membrane protein anchoring:
Specific proteins can be covalently attached via a carbohydrate bridge to
membrane bound PI.
Examples : Alkaline phosphatase (a digestive enzyme found on the surface of the
small intestine that attacks organic phosphates), and acetyl-choline esterase (an
enzyme of the post-synaptic membrane that degrades the neurotransmitter
acetyl choline).
Cell surface proteins bound to glycosyl phosphatidyl inositol (GPI) are also
found in variety of parasitic protozoans (eg. trypanosomes and leishmania) being
attached to a membrane lipid (rather than being an integral part of the
membrane) allows GPI-anchored proteins rapid lateral mobility on the
surface of the plasma membrane.
43

44. The protein can be cleaved from its anchor by the action of
phopholipase C, releasing diacylglycerol.
[A deficiency in the synthesis of GPI in hematopoietic cells results in
a hemolytic disease, paroxysmal nocturnal hemoglobinuria.]
44

45. 45

46. Sphingolipids:
Structure and importance of sphingomyelin

47. 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 glycol-1lipids.
The alcohol group at carbon1 of sphingosine is esterified to
phosphoryl choline, producing sphingomyelin, the only;
significant sphingo phospholipid in humans.
Sphingomyelin is an important constituent of the myelin of
nerve fibers.
47

48. [The myelin sheath is a layered,membranous structure that
insulates and protects neuronal fibers of the central Nervous
system.]
48

49. Degradation of sphingomyelin
• Sphingomyelin degraded by sphingomyelinase, a lysosomal
enzyme that hydrolytically removes phosphorylcholine,
leaving ceramide.
• The ceramide is, in turn, cleaved by ceramidase into
sphingosine and a free fatty acid.
• The ceramide and sphingosine released by the degradation of
sphingomyelin play a role as intracellular messengers.
Ceramide is appear to be involved
49

50. Niemann-Pick Disease
Disease (Types A and B):
sphingomyelinase—
a type of phospholipase C
50

51. Glycosphingolipids
The glycosphingolipids differ from sphingomyelin in that
they do not contain phosphate, and the polar head function
is provided by 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.
51

52. Neutral glycosphingolipids
The simplest neutral (uncharged) glycosphingolipids are the
cerebrosides.
These are ceramide monosaccharides that contain either a
molecule of galactose (galactocerebroside—the most
common cerebroside found in membranes, or glucose
(glucocerebroside, which serves primarily as an intermediate
in the synthesis and degradation of the more complex
glycosphingolipids).
The cerebrosides are found predominantly in the brain and
peripheral nervous tissue, with high concentrations in the
myelin sheath.
Ceramide oligosaccharides (orglobosides) are produced by
attaching additional monosaccharides (including GalNAc) to
a glucocerebroside. 52

53. • Cerebroside (glucocerebroside : Cer-Gic
• Globoside (lactosylceramide): Cer-Glc-Gal
• Globoside (Forssman antigen): Cer-Glc-Gal-Gal-GalNac-
GalNac
53
Examples:

54. Acidic glycosphingolipids
Acidic glycosphingolipids are negatively charged at
physiologic pH. The negative charge is provided by N-
acetyl neuraminicacid (NANA , = sialic acid) in
gangliosides, or by sulfate groups in sulfatides.
1. Gangliosides: These are the most complex
glycosphingolipids, and are found primarily in the ganglion
cells of the central nervous system, particularly at the nerve
endings.
They are derivatives of ceramide oligosaccharides, and
contain one or more molecules of NANA.
54

55. 55
The notation for these compounds
is G (for ganglioside), plus a
subscript M, D, T, or Q to
indicate whether there is one
(mono), two, three, or four
(quatro) molecules of NANA
in the ganglioside,
respectively.
Additional numbers and letters
in the subscript designate the
sequence of the carbohydrate
attached to the ceramide.

56. Sulfatides:
Sulfoglycosphingolipids (sulfatides) are cerebrosides that
contain sulfated galactosyl residues, and are therefore
negatively charged at physiologic pH.
Sulfatides are found predominantly
in nerve tissue and kidney.
56

57. The sphingolipidoses:
• Autosomal recessive diseases, except for Fabry disease, which is X-linked.
• The incidence of the sphingolipidoses is low in most populations, except for
Gaucher and Tay-Sachs diseases.
• Like Niemann-Pick disease, show a high frequency in the Ashkenazi Jewish
population.
Diagnosis and treatment:
• by measuring enzyme activity in cultured fibroblasts or peripheral leukocytes, or
by analysis of DNA.
• Histologic examination of the affected tissue.
Symptoms: Shell-like inclusion bodies are seen in Tay-Sachs
Wrinkled tissue paper appearance of the cytosol is seen in Gaucher.
Prenatal diagnosis: using cultured amniocytes or chorionic villi.
The sphingolipid accumulates in the lysosomes in each disease. It cannot be degraded as a result
of the specific enzyme deficiency.
57

58. 58
Gaucher disease :
 Macrophages become enlarged with glucocerebroside.
Fabry disease:
 Globosides accumulate in the vascular endothelial lysosomes of the brain, heart,
kidneys, and skin.
 Have been successfully treated by
recombinant human enzyme replacement therapy.
Gaucher can be treated by
bone marrow transplantation
(because macrophages are derived from
hematopoietic stem cells).

59. 59
Degradation of sphingolipids and
missing enzymes

60. 60

61. 61

62. Lipid mediators

63. Lipid mediators
Lipid mediators are bioactive molecules rapidly produced upon cell activation
either by enzymatic process or by oxidative fragmentation of polyunsaturated
fatty acids attached to their glycerol backbone.
The majority of lipid mediators are products of degradation and/or
phosphorylation/dephosphorylation of glycerophospholipids by defined enzymes
Usually, phospholipases (PLs), phosphokinases, and phosphatases.
Hydrolysis of phospholipids also generates free fatty acids, including
arachidonate, a direct precursor of eicosanoids.
Upon cell activation, Some phospholipids are selectively hydrolyzed by
phospholipases results in production of highly bioactive molecules (lipids and/or
fatty acids).
Sometimes phosphorylated by specific kinases to
bioactive phosphoinositides Inositol lipids.
The three phospholipase (PL) families of Phospholipase A2 (PLA2)

64. Aberrant immune responses by
• Allergens, environmental pollutants, Infectious agents, Acids and other noxious
stimuli
This promotes excessive leukocyte recruitment and the production of pro-
inflammatory cytokines, lipids mediators, and Chemokines
These are critical to initiate and maintain the inflammatory process.
Lipoxins (LXs), derived from the omega-6 PUFA arachidonic acid, harbor
potent anti-inflammatory activity and promote the resolution of inflammation.
e.g for lipid mediators :
 leukotrienes (LTs)
 prostaglandins (PGs)
Lipoxins (LXs)

65. Generation of lipid mediators and their function
Invading microbe or exogenous chemical signal
The immunological consequences of omega-3-derived specialized proresolving
mediators (SPMs).
The role of the arachidonic acid-derived prostaglandins, lipoxins
The sequential release of mediators (including histamine, bradykinin, and 5-
hydroxytryptophan [5HT]).
This leads to the immediate influx of polymorphonuclear leukocytes (PMNs)
followed by phagocytosis.
 phagocytosis via monocytes-macrophages, leading to leukocyte clearance and
resolution.

69. THE EICOSANOIDS

70. Definition & classification
• Eicosanoids is a family of very potent biological signalling molecules are
originated from polyunsaturated fatty acids with twenty carbons
(arachidonate) known as eicosanoids.
• They act as short-range messengers affecting tissues near the cells that
produce them.
3 subclasses of eicosanoids:
1. Prostaglandins
2. Thromboxanes and
3. leukotrienes

71. Prostaglandins and related compounds
• Prostaglandins(PG), and related compounds thromboxanes (TX) and
leukotrienes(LT), are collectively known as eicosanoids as they reflect their
origin from polyunsaturated fatty acids with twenty carbons.
• They are extremely potent compounds that elicit a wide range of responses,
both physiologic and pathologic.
• Although, compared to hormones in terms of their actions, eicosanoids differ
from the true hormones.
• They are produced in very small amounts in almost all tissues rather than in
specialized glands.
• They also act locally rather than after transport in the blood to distant sites, as
occurs with true hormones such as insulin.
71

72. • These signalling molecules generally do not move far from the tissue that
produced them and act primarily on cells very near their point of release.
• Eicosanoids are not stored, and they have an extremely short half-life, being
rapidly metabolized to inactive products at their site of synthesis.
• Their biologic actions are mediated by plasma and nuclear membrane
receptors, which are different in different organ systems.
72

73. Nomenclature of eicosanoids
Fatty acid sources
• "Eicosanoid" (eicosa-, Greek - "twenty") is the collective term for straight-chain
polyunsaturated fatty acids (PUFAs) of 20 carbon units in length.
• They are metabolized or otherwise converted to oxygen-containing products.
• The PUFA precursors to the eicosanoids include:
Arachidonic acid (AA), i.e. 5, 8,11,14-eicosatetraenoic acid is ω-6 fatty acid,
with four double bonds in the cis configuration each located between carbons 5-
6, 8-9, 11,-12, and 14-15.
• Adrenic acid (AdA), 7,10,13,16-docosatetraenoic acid, is an ω-6 fatty acid with
four cis double bounds, each located between carbons 7-8, 10-11, 13-14, and 17-
18.

74. • Eicosapentaenoic acid (EPA): i.e. 5, 8,11,14,17-eicosapentaenoic acid is an ω-3
fatty acid with five cis double bonds, each located between carbons 5-8, 8-9, 11,-
12, 14-15, and 17-18.
• Dihomo-gamma-linolenic acid (DGLA) : 8, 11,14-eicosatrienoic acid is an ω-6
fatty acid with three cis double bonds, each located between carbons 8-9, 11,-12,
and 14-15.
• Mead acid : i.e. 5,8,11-eicosatrienoic acid, is an ω-9 fatty acid containing three
cis double bonds, each located between carbons 5-6, 8-9, and 11,-12.

75. Synthesis of Eicosanoids

76. Synthesis of prostaglandins and thromboxanes
The dietary precursor of the prostaglandins is the essential fatty acid, linoleic
acid.
It is elongated and desaturated to arachidonic acid, the immediate precursor of
the predominant class of prostaglandins in humans.
Arachidonic acid is released from membrane-bound phospholipids by
phospholipase A2 in response to a variety of signals
Synthesis of PGH2: The first step in the synthesis of prostaglandins is the
oxidative cyclization of free arachidonic acid to yield PGH2 by prostaglandin
endoperoxide synthase.
This enzyme is a microsomal protein, has two catalytic activities: fatty acid
cyclo oxygenase (COX) and peroxidase, which is dependent on reduced
glutathione
76
Location : smooth endoplasmic reticulum

77. Isozymes of prostaglandin endoperoxide synthase:
The two isozymes, usually denoted as COX-1 and COX-2, of the synthase are
known.
COX-l is made constitutively in most tissues, and is required for maintenance of
healthy gastric tissue, renal homeostasis, and platelet aggregation.
COX-2 is inducible in a limited number of tissues in response to products of
activated immune and inflammatory cells.
[The increase in prostaglandin synthesis subsequent to the induction of COX-2
mediates the pain, heat, redness, and swelling of inflammation, and the fever of
infection.]
77

78. Thromboxane synthesis:
• PGH2 is enzymatically converted into thromboxane A2, from which other
thromboxanes are derived.
• This reaction is catalyzed by thromboxane synthase, an enzyme present in blood
platelets( = thrombocytes).
• Thromboxanes induce blood vessel constriction and platelet aggregation, the
early steps in blood clotting.
• Thromboxanes and prostaglandins both contain a ring of 5 or 6 atoms.
• The pathway that leads from arachidonate to these two classes of compounds is
sometimes called the ‘cyclic’ pathway – in order to differentiate it from the
‘linear’ pathway that results in the synthesis of the ‘linear’ molecules of
leukotrienes from arachidonate

79. A. Production of PGH2
from arachidonate by the
action of prostaglandin
endoperoxide synthase
B. Inhibitory action of
aspirin
C. Structure of ibuprofen

80. Inhibition of prostaglandin synthesis :
The synthesis of prostaglandins can be inhibited by a number of unrelated
compounds.
Eg. Cortisol (a steroidal anti-inflammatory agent) inhibits phospholipase A2
activity, so arachidonic acid, is not available.
Cortisol also inhibits COX-2, but not COX-1
Aspirin, indomethacin, and phenylbutazone (all nonsteroidal antinflammatory
agents or NSAIDs) inhibit both COX1 and COX-2 and, therefore, prevent the
synthesis of the parent prostaglandin, PGH2.
Aspirin's toxicity: Systemic inhibition of COX-1 with subsequent damage
to the stomach and the kidneys, and impaired clotting of blood.
Inhibitors specific for COX-2 (e.g.celecoxib-1) are designed to reduce
pathologic inflammatory processes while maintaining the physiologic functions of
COX-1.
80

81. 81

82. Synthesis of Leukotrienes:
The lipo-oxygenase pathway
Arachidonic acid is converted to a variety of linear hydroperoxy acids by a
separate pathway involving a family of lipoxygenases.
e.g., neutrophils contain 5-lipoxygenase, which converts arachidonic acid to 5-
hydroperoxy-6,8,11,14 eicosa tetraenoic acid (5-HPETE).
5-HPETE is converted to a series of leukotrienes, the nature of the final
products varying according to the tissue.
 Lipoxygenases are not affected by NSAIDS.
Leukotrienes are mediators of allergic response and inflammation.
[Inhibitors of 5-lipoxygenase and leukotriene receptor antagonists are used in the treatment of
asthma.]
82

83. • Leukotriene synthesis begins with the incorporation of molecular oxygen
into arachidonate by the enzymatic action of the mixed-function oxidases
called lipoxygenases.
• The lipoxygenases are found in leukocytes and in heart, brain, lung and
spleen, and utilize cytochrome P-450 for their acitvity.
• The various leukotrienes differ in the position of the peroxide that is
introduced by these lipoxygenases.
• Unlike the cyclic pathway, this linear pathway for leukotriene synthesis is not
inhibited by aspirin or ibuprofen.

85. Release of membrane arachidonic acid
(stimulators, inhibitors)

86. The cyclo-oxygenase pathway, steroid,
nonsteroidal drugs

87. 87
 Aspirin is anti-thrombogenic effect.
 It inhibits thromboxaneA2 synthesis from arachidonic
acid in platelets by irreversible acetylation and inhibition
of COX-1.
 This irreversible inhibition of COX-1 cannot be
overcome in a nucleate platelets,
 Can be overcome in endothelial cells, because they have a
nucleus and, therefore, can generate more of the enzyme.
 This difference is the basis of low dose aspirin therapy
used to lower the risk of stroke and heart attacks by
decreasing formation of thrombi.

88. 88

89. 89

90. 90

91. Physiological effects of eicosanoids
Eicosanoids are involved in physiologic functions:
- ovarian and uterine function
- bone metabolism
- nerve and brain function
- smooth muscle regulation
- platelet homeostasis

92. Role of prostaglandins in platelet homeostasis:
they play roles in mediating
• Inflammation
• Fever
• Allergic response
• Ensuring gastric integrity
• Renal function.
92
Effects of prostaglandins, thromboxanes, & prostacyclins

93. Thromboxane A2 (TXA2) - produced by activated platelets. It promotes
- adherence and aggregation of circulating platelets
- contraction of vascular smooth muscle, thus promoting formation of blood
clots (thrombi).
Prostacyclin (PGI2)
- produced by vascular endothelial cells,
- inhibits platelet aggregation and
- stimulates vasodilation, so impedes thrombogenesis.
- The opposing effects of TXA2 and PGI2 limit thrombi formation to sites of
vascular injury.

94. Effects of leukotriens & HETE
• Leukotrienes are mediators of allergic response and
• Inflammation .

95. Thank you…!