Download Lipids lecture(4) by Prof.Dr.Moaed Al

2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
Phospholipids
They contain glycerol, fatty acids and a nitrogenous base.
A.Phosphatidates:
i. These are derivatives of phosphatidic acid which is the simplest
phospholipid.
ii. 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.
iii. The molecule has an asymmetric carbon atom and therefore,
exhibits optical isomerism. L-isomer is found in nature.
B. Amphipathic Nature:
Phospholipids
in
general
are
amphipathic,
particularly
Lecithin. They have both hydrophobic and hydrophilic portion in
their molecule . 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'.
2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
C. Micellar Formation
When phospholipids are distributed in water, their hydrophobic
parts keep away from water, forming molecular aggregates called
micelle . These are involved in solubilization of lipids in aqueous
media and help in digestion and absorption of lipids.
D. 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 . 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.
Drugs,
proteins,
enzymes,
genes,
etc.
may
be
2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
encapsulated by the liposomes which could act as carriers for
these substances to target organs.
Liposomes have important applications in cancer chemotherapy,
antimicrobial therapy, gene therapy, vaccines and diagnostic
imaging.
E. Biomembranes
The molecules align themselves to form monolayers with the
polar heads pointing in one direction and the nonpolar tails in the
opposite direction . 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. They also act as detergents and
emulsifying agents. In vivo, they act as pulmonary
surfactants.
1. Phosphatidyl choline or Lecithin
i. This is a nitrogen containing phospholipid. The word lecithin is
derived from the Greek word, lekithos = egg yolk. It contains
glycerol.
ii. The alpha and beta positions are esterified with fatty acids.
Usually the fatty acid attached to the beta-carbon is a PUFA
molecule .
iii. The phosphoric acid is added to the third position, to form
phosphatidic acid. The phosphate group is esterified to the
quaternary nitrogen base, Choline . The molecules of lecithin exist
as zwitterions (pl = 6.7).
Action of Phospholipases
2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
Phospholipases are enzymes that hydrolyse phospholipids.
Different phospholipases are involved in the hydrolysis of specific
bonds in lecithin . Phospholipase A2 acts on an intact lecithin
molecule hydrolysing 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.
The products formed in each case may be summarized as follows:
Phospholipase A2
Lecithin ——————→
Lysolecithin + fatty acid
Phospholipase A1
Lecithin ——————→ Acyl glycerophosphorylcholine+ fatty acid
Phospholipase C
Lecithin ——————→
1,2 diacyl glycerol + Phosphoryl choline
Phospholipase D
Lecithin ——————→
Lung Surfactants
Phosphatidic acid +choline
2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
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. 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.
The lecithin-sphingomyelin (LS) ratio of amniotic fluid is an index of
fetal maturity. A ratio of 2 indicates full lung maturity. Low levels of
surfactant leads to respiratory distress syndrome (RDS), which is a
common cause of neonatal morbidity.
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.
2. Phosphatidyl ethanolamine 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.
3. Phosphatidyl inositol
2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
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
4. Plasmalogens
These are phospholipids which have an aliphatic long chain α − β
unsaturated alcohol in ether linkage with the first hydroxyl group of
glycerol .
The second OH group is esterified to a fatty acid. The phosphoric
acid is attached to choline or ethanolamine . The alcohols have
about C12 to C18 chain length. Plasmalogens are found in
biomembranes in brain and muscle.
5. Phosphatidyl Glycerol
2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
It is formed by esterification of phosphatidic acid to glycerol. When
two molecules of phosphatidic acid are linked with a molecule of
glycerol, diphosphatidyl glycerol or cardiolipin is formed. 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.
6. Sphingolipids
The
sphingosine
containing
phosphosphingosides,
lipids
may
glycosphingolipids
be
and
of
3
types;
sulfatides.
All
sphingolipids have the long aliphatic amino alcohol sphingosine
which is attached to a fatty acid in amide linkage to form
aceramide . The fatty acid has a chain length varying from C18 to
C24.
7. Phosphosphingosides
They
contain
phosphoric
acid
group.
A
common
phosphosphingoside present abundantly in bio membranes,
especially of the nervous system, is sphingomyelin. It contains
choline .
2016
Lipids lecture(4) by Prof.Dr.Moaed Al-Gazally
Sphingomyelins
Sphingomyelins
are
the
only
sphingolipid
that
contain
phosphate and have no sugar moiety.
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 .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.