Metabolism of phospholipids

Gandham.Rajeev
Email:gandhamrajeev33@gma
il.com
 Phospholipids

Phospholipids are a specialized group of

lipids performing a variety of functions.
These include the membrane structure &
functions, involvement in blood clotting &
supply of arachidonic acid for the
synthesis of prostaglandins.
Phosphilipids
 Synthesis of phospholipids

Phospholipids are synthesized from

phosphatidic acid & 1,2-diacylglycerol,
intermediates in the production of
triacylglycerols.
Phospholipids synthesis occurs in the
smooth endoplasmic reticulum.
Inner mitochondrial membrane
 Synthesis of Glycerophosphatides

Phosphatidic acid is an important intermediate

in the synthesis of phosphoglycerides & TAG.
The phosphatidic acid itself may be formed
from glycerol-3-phosphate or DHAP.
The synthesis of glycerophospholipids can
occur either by activation into CDP-choline &
CDP-ethanolamine or by formation of active
diacylglycerol, CDP-diacylglycerol.
 Formation of lecithin & cephalin

It occurs mainly in liver & brain.

Choline & ethanolamine first get
phosphorylated & then combine with CTP
to form, CDP-choline & CDP-ethanolamine.
Phosphatidylcholine (lecithin) is
synthesized when CDP-choline combines
with 1,2-diacylglycerol.
 Phosphatidyl ethanolamine (cephalin) is
produced when CDP-ethanolamine reacts
with1,2-diacylglycerol.
Phosphatidyl ethanolamine can be converted
to phosphatidyl choline on methylation.
Phosphatidylcholine Phosphatidylethanolamine
 Synthesis of phosphatidylserine

Phosphatidyl ethanolamine can exchange

its ethanolamine group with free serine to
produce phosphatidylserine.
On decarboxylation, gives phosphatidyl
ethanolamine.
Phosphatidylserine
 Formation of phosphatidylinositol

CDP-diacylglycerol produced from

phosphatidic acid combines with inositol to
form phosphatidyl inositol (Pl).
Phosphatidyl inositol contains arachidonic
acid on carbon 2 of glycerol which serves
as, a substrate for prostaglandin synthesis.
PI is important for signal transmission
across membranes.
Phosphatidylinositol
 Synthesis of phosphatidyl glycerol &
cardiolipin
CDP-diacylglycerol combines with glycerol
3-phosphate to form phosphatidyl glycerol
3-phosphate, which forms
phosphatidylglycerol.
The phosphatidylglycerol combines with
another molecule of phosphatidylglycerol
to produce cardiolipin.
Cardiolipin possess antigenic properties.
Phosphatidylglycerol
 Formation of plasmalogens

These are phospholipids with fatty acid at

carbon 1 bound by an ether linkage
instead of ester linkage.
An important plasmalogen, 1-alkenyl 2-
acetyl glycerol 3 phosphocholine, causes
blood platelet aggregation & is referred to
as platelet activating factor (PAF).
 Synthesis of sphingomyelins
These are phospholipids containing a
complex amino alcohol, sphingosine instead
of glycerol.
Palmitoyl CoA & serine combine & undergo a
sequence of reactions to produce sphingosine
which is then acylated to produce ceramide.
Sphingomyelin is synthesized when ceramide
combines with CDP-choline.
Sphingomyelin
 Degradation of
Phospholipids
Phospholipids are degraded by
phospholipases which cleave the
phosphodiester bonds.
Four types of phospholipases.
Phospholipase A1
Phospholipase A2
Phospholipase C
Phospholipase D
 Degradation of
Phospholipids
Phospholipase A1:

It specifically cleaves the fatty acid at C1

position of phospholipids resulting in
lysophospholipid.
These are further acted by
lysophospholipase, phospholipase B to
remove the second acyl group at C2
position.
Degradation of phospholipids
 Phospholipase A2 hydrolyses the fatty acid

at C2 position of phospholipids.
Snake venom & bee venom are rich
sources of phospholipase A2.

Phospholipase A2 acts on phosphatidyl

inositol to liberate arachidonic acid, the
substrate for the synthesis of
prostaglandins.
 Phospholipase C specifically cleaves the bond
between phosphate & glycerol of
phospholipids.
Phospholipase C is present in lysosomes of
hepatocytes.
Phospholipase D hydrolyses & removes the
nitrogenous base from phospholipids.
The degraded products of phospholipids enter
the metabolic pool & utilized for various
purposes.
 Role of LCAT in lecithin
metabolism

Lecithin-cholesterol acyltransferase (LCAT)

is plasma enzyme.
Synthesized in liver.
LCAT activity is associated with apoA1 of
HDL.
LCAT esterifies cholesterol by transferring
acyl group from the second position of
lecithin.
 LCAT
Lecithin + Cholesterol Lysolecithin + Cholesterol
ester

It is responsible for the reverse cholesterol

transport mediated by HDL
HDL is a good cholesterol.
 Degradation of
sphingomyelins
Sphingomyelinase of lysosomes hydrolyses
sphingomyelins to ceramide & phosphoryl
choline.
Ceramide is further degraded to
sphingosine & free fatty acid.

Sphingomyelina
Ceramide Phosphoryl
se
(sphingosine - choline
FFA) Action of
sphingomyelinase &
Ceramidase ceramidase on
sphingomyelin
 Metabolism of
glycolipids
Glycolipids are derivatives of ceramide
(sphingosine bound to fatty acid),
commonly called ad glycosphongolipids.
The simplest form of glycosphingolipids
are cerebrosides containing ceramide
bound to monosaccharides.
 Galactocerebroside (Gal-Cer) &
glucocerebroside (Glu-Cer) are the common
glycosphingolipids.
Galactocerebroside is present in nervous
tissue.
Glucocerebroside is an intermediate in
synthesis & degradation of
glycosphingolipids
Biosynthesis of cerebrosides &
sulfatides
Sphingosin
e
Acyl
CoA
CoA
UDP- UDP-
Ceramide
Galactose Glucose
UDP UDP

Galactocerebrosi Glucocerebrosid
de e
PAPS

Galactocerebroside 3-
sulfate
Degradation of cerebrosides &
sphingomyelins
Galactocerebroside

- Galactosidase
Galactose
Glucose Fatty acid
Ceramid
Glucocerebroside Sphingosine
e
- Glucosidase Ceramidase

Choline -P
Sphingomyelinase

Sphingomyeli
n
 References
Textbook of Biochemistry-U Satyanarayana

Textbook of Biochemistry-DM Vasudevan

Textbook of Biochemistry-MN Chatterjea

Thank You