- Phospholipids are amphipathic lipids that contain fatty acids, glycerol, and a phosphate group. They form bilayer structures in cell membranes. - Examples include phosphatidylcholine (lecithin), sphingomyelin, phosphatidylethanolamine. They play important structural and functional roles in membranes. - Phospholipids can form micelles and liposomes in aqueous solutions due to their amphipathic nature. Liposomes are used as carriers for drug delivery. - Lung surfactants contain lecithin and help reduce surface tension in the lungs. Deficiencies can cause respiratory distress in infants.

1. Chemistry of Lipids
PHOSPHOLIPIDS Part – 2
V.S.RAVI KIRAN

2. V.S.RAVIKIRAN, MSc.,
Department of Biochemistry,
ASRAM Medical college,
Eluru-534005.AP, India.
vsravikiran2013@gmail.com

3. PHOSPHOLIPIDS
• They contain glycerol, fatty acids and a nitrogenous base.
• Lecithin, was discovered in 1870 by the German biochemist Ernst
Hoppe- Selyer.
• Strecker characterized choline in 1861.
• In 1884, Thudichum JLW described sphingosine, sphingomyelin,
cerebrosides, cephalin and lecithin in brain tissue.

4. Phosphatidates
• These are derivatives of phosphatidic acid, which is the simplest
phospholipid.
• Phosphatidic acid is made up of one glycerol to which two fatty acid
residues are esterified to carbon atoms 1 and 2. The 3rd hydroxyl
group is esterified to a phosphoric acid.
L-Phosphatidic acid

5. Phosphatidates
• The molecule has an asymmetric carbon atom and therefore, exhibits
optical isomerism.
• L-isomer is found in nature.

6. Amphipathic Nature
• Phospholipids in general are amphipathic, particularly Lecithin.
• They have both hydrophobic and hydrophilic portion in their
molecule.

7. Amphipathic Nature
Phospholipids form the bilayer

8. Amphipathic Nature
Phospholipids form micelles and liposomes

9. Amphipathic Nature
• The glycerol along with the phosphoric acid and choline constitute
the polar ‘head' of a phospholipid molecule, whereas the
hydrocarbon chains of the fatty acids represent the nonpolar ‘tail'.

10. Micellar Formation
• When phospholipids are distributed in water, their hydrophobic parts
keep away from water, forming molecular aggregates called micelle.
Phospholipids form micelles and liposomes

11. Micellar Formation
• These are involved in solubilization of lipids in aqueous media and
help in digestion and absorption of lipids.

12. Liposomes
• A lipid bilayer will close on itself under appropriate conditions to form
liposomes. Unilamellar or multilamellar liposomes may be formed.
They may be prepared by sonication of mixtures of phospholipids and
cholesterol.
Phospholipids
form micelles
and liposomes

13. Liposomes
• Liposomes are microscopic spherical vesicles.
• When mixed in water under special conditions, the phospholipids
arrange themselves to form a bilayer membrane which encloses some
of the water in a phospholipid sphere.

14. Liposomes
• Drugs, proteins, enzymes, genes, etc. may be encapsulated by the
liposomes which could act as carriers for these substances to target
organs.
• Liposome-entrapped drugs exhibit superior pharmacological
properties than those observed with conventional formulations.

15. Liposomes
• Liposomes have important applications in -
cancer chemotherapy,
antimicrobial therapy,
gene therapy,
vaccines and diagnostic imaging.

16. Aquasomes
• They are one of the most recently developed delivery systems that
are making a niche as the peptide/protein carriers.
• These are nano particulate carrier systems with three layered self-
assembled structures

17. Aquasomes
• They comprise the central solid nanocrystalline core coated with
polyhydroxy oligomers onto which biochemically active molecules are
adsorbed.
• The solid core provides the structural stability.
• The carbohydrate coating stabilizes the biochemically active molecules.
• As the conformational integrity of bioactive molecules is maintained,
aquasomes are being proposed as a carrier system for delivery of peptide
based pharmaceuticals.

18. Aquasomes
• The delivery system has been successfully utilized for the delivery of
insulin, hemoglobin and various antigens.
• Oral delivery of enzymes like serratiopeptidase has also been
achieved.

19. Biomembranes
• The molecules align themselves to form monolayers with the polar
heads pointing in one direction and the nonpolar tails in the opposite
direction. Phospholipids form the bilayer

20. Biomembranes
Phospholipids form micelles and liposomes

21. Biomembranes
• Only fatty acids with more than 6 carbon atoms form monolayers.
This explains their role as components of biomembranes.
• The self-assembly of phospholipids into bilayers is driven by
hydrophobic interaction.

22. Biomembranes
• They also act as detergents and emulsifying agents.
• In vivo, they act as pulmonary surfactants.

23. Phosphatidylcholine or Lecithin
• This is a nitrogen containing phospholipid.
• The word lecithin is derived from the Greek word, lekithos = egg yolk.
• It contains glycerol.

24. Phosphatidylcholine or Lecithin
• The alpha and beta positions are esterified with fatty acids.
• Usually, the fatty acid attached to the betacarbon, is a PUFA
molecule.

25. Phosphatidylcholine or Lecithin
Lecithin R1 and R2 are
fatty acids.
Red rectangle depicts
glycerol group.
The blue rectangle is
choline which shows
polar or hydrophilic
property

26. Phosphatidylcholine or Lecithin
• The phosphoric acid is added to the third position, to form
hosphatidic acid. The phosphate group is esterified to the quaternary
nitrogen base, Choline.
Lecithin R1 and R2 are fatty
acids.
Red rectangle depicts
glycerol group.
The blue rectangle is choline
which shows polar
or hydrophilic property

27. Phosphatidylcholine or Lecithin
• The molecules of lecithin exist as zwitterions (pl = 6.7).

28. Action of Phospholipases
• Phospholipases are enzymes that hydrolyze phospholipids. Different
phospholipases are involved in the hydrolysis of specific bonds in
lecithin

29. Action of Phospholipases
• Phospholipase A2 acts on an intact lecithin molecule hydrolyzing the
fatty acid esterified to the beta (second) carbon atom.
• The products are Lysolecithin and fatty acid.
• Lysolecithin is a detergent and hemolytic agent.
• The enzyme is present in the venom of viper snakes.
• The hemolysis and consequent renal failure seen in viper poisoning
could be thus explained.

30. Action of Phospholipases
• Actions of other phospholipases are shown in Figure. The
products formed in each case may be summarized as follows:
Phospholipase A2
 Lecithin Lysolecithin + fatty acid
Phospholipase A1
 Lecithin 1 Acyl glycerophosphorylcholine + fatty acid
Phospholipase C
 Lecithin 1,2 diacylglycerol + Phosphoryl choline
Phospholipase D
 Lecithin Phosphatidic acid + choline

31. Lung Surfactants
• Normal lung function depends on a constant supply of lung
surfactants.
• It is produced by epithelial cells.
• It decreases surface tension of the aqueous layer of lung and prevents
collapse of lung alveoli.

32. Lung Surfactants
• Constituents of surfactants are dipalmitoyl lecithin, phosphatidyl
glycerol, cholesterol and surfactant proteins A, B and C.
• During fetal life, the lung synthesizes sphingomyelin before 28th week
of gestation.
• But as fetus matures, more lecithin is synthesized.

33. Lung Surfactants
• The lecithin-sphingomyelin (LS) ratio of amniotic fluid is an index of
fetal maturity.
• A ratio of 2 indicates full lung maturity.
• Low surfactant level can lead to respiratory distress syndrome (RDS),
which is a common cause of neonatal morbidity

34. Respiratory Distress Syndrome (RDS)
• It is due to a defect in the biosynthesis of dipalmitoyl lecithin (DPL),
the main pulmonary surfactant.
• Premature infants have a higher incidence of RDS because the
immature lungs do not synthesize enough DPL.

35. Phosphatidylethanolamine or Cephalin
• Cephalin differs from lecithin in that the nitrogen base ethanolamine
is present instead of choline. Cephalin is also found in biomembranes
and possesses amphipathic properties.
Cephalin (Phosphatidylethanolamine)

36. Phosphatidylinositol
• Here, phosphatidic acid is esterified to inositol. Phosphatidyl inositol
bisphosphate or PIP2 is present in biomembranes.
• This compound plays a vital role in the mediation of hormone action
on biomembranes and acts as a second messenger.
Phosphatidylinositol

37. Plasmalogens
• These are phospholipids which have an aliphatic long chain α-β
unsaturated alcohol in ether linkage with the first hydroxyl group of
glycerol.
Ethanolamine plasmalogen

38. Plasmalogens
• The second OH group is esterified to a fatty acid.
• The phosphoric acid is attached to choline or ethanolamine.
Ethanolamine plasmalogen

39. Plasmalogens
• The alcohols have about C12 to C18 chain length.
• Plasmalogens are found in biomembranes in brain and muscle.
Ethanolamine plasmalogen

40. Phosphatidylglycerol
• It is formed by esterification of phosphatidic acid to glycerol.
• When two molecules of phosphatidic acid are linked with a molecule
of glycerol, diphosphatidylglycerol or cardiolipin is formed.

41. Phosphatidylglycerol
• It is the major lipid of mitochondrial membrane. Commercially, it is
extracted from myocardium.
• Decreased cardiolipin level leads to mitochondrial dysfunction, and is
accounted for-
• Heart failure,
• hypothyroidism and
• some types of myopathies.

42. Sphingolipids
• The sphingosine containing lipids may be of 3 types;
• phosphosphingosides,
• glycosphingolipids and
• sulfatides.

43. Sphingolipids
• All sphingolipids have the long aliphatic amino alcohol sphingosine
which is attached to a fatty acid in amide linkage to form a ceramide.
• The fatty acid has a chain length varying from C18 to C24.
Sphingosine

44. Sphingolipids
• All sphingolipids have the long aliphatic amino alcohol sphingosine
which is attached to a fatty acid in amide linkage to form a ceramide.
• The fatty acid has a chain length varying from C18 to C24.
Ceramide

45. Phosphosphingosides
• They contain phosphoric acid group.
• A common phosphosphingoside present abundantly in
biomembranes, especially of the nervous system, is sphingomyelin. It
contains choline.
Sphingomyelin

46. Sphingomyelins
• Sphingomyelins are the only sphingolipid that contain phosphate
and have no sugar moiety.
• They are found in large quantities in nervous system.

47. Sphingomyelins
• They are found in large quantities in nervous system.
• Different sphingomyelins may be formed depending on the fatty acid
attached.
• Common fatty acids found are—
• lignoceric (24 C),
• nervonic (24 C, one double bond) and
• cervonic (22 C, 6 double bonds) acids.

48. Sphingomyelins
• Because of its amphipathic nature sphingomyelin can act as an
emulsifying agent and detergent.
• The relative proportion of lecithin and sphingomyelin is important in
biological fluids like bile, amniotic fluid, etc.
• Sphingomyelin combined with fatty acid is called ceramide, which is a
component of glycosphingolipids.

49. Clinical relevance of antiphospholipid antibody is
described in Box.

50. Non-phosphorylated Lipids
• Glycosphingolipids (Glycolipids)
• They are seen widely in nervous tissues. This group of lipids do not
contain phosphoric acid; instead they contain carbohydrates and
ceramide.
• Ceramide + Glucose → Glucocerebroside
• Ceramide + Galactose → Galactocerebroside

51. Globosides (Ceramide Oligosaccharides)
• They contain two or more hexoses or hexosamines, attached to a
ceramide molecule.
• Ceramide + Galactose + Glucose → Lactosyl ceramide
• Lactosyl ceramide is a component of erythrocyte membrane.

52. Gangliosides
• They are formed when ceramide oligosaccharides have at least one
molecule of NANA (N-acetyl neuraminic acid) (sialic acid) attached to
them.
• Ceramide—Glucose—galactose—NANA;
• This is designated as GM3 (ganglioside M3).

53. Gangliosides
• Gangliosides contribute to stability of paranodal junctions and ion
channel clusters in myelinated nerve fibers.
• Autoantibodies to GM1 disrupt lipid rafts, paranodal or nodal
structures, and ion channel clusters in peripheral motor nerves.

54. Sulfolipids or Sulfatides
• These are formed when sulfate groups are attached to ceramide
oligosaccharides.
• All these complex lipids are important components of membranes of
nervous tissue.

55. Sulfolipids or Sulfatides
• Failure of degradation of these compounds results in accumulation of
these complex lipids in CNS.
• This group of inborn errors is known as lipid storage diseases.

56. THANK YOU