The document summarizes metabolism of phospholipids. Phospholipids are synthesized from phosphatidic acid and diacylglycerol in the smooth endoplasmic reticulum and mitochondrial membranes. They perform important structural and signaling functions. Phospholipids are broken down by phospholipases which cleave phosphodiester bonds. The degraded products enter metabolic pools and are used for various purposes. Lecithin-cholesterol acyltransferase also plays a role in cholesterol transport.
2. • 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.
3.
4. • 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
5. • 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.
6.
7. • 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.
8. • Phosphatidyl ethanolamine (cephalin) is
produced when CDP-ethanolamine reacts
with1,2-diacylglycerol.
• Phosphatidyl ethanolamine can be converted
to phosphatidyl choline on methylation.
9.
10. • Phosphatidyl ethanolamine can exchange
its ethanolamine group with free serine to
produce phosphatidylserine.
• On decarboxylation, gives phosphatidyl
ethanolamine.
11.
12. • 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.
13.
14. • 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.
15.
16. • 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).
17. • 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.
18.
19. • Phospholipids are degraded by
phospholipases which cleave the
phosphodiester bonds.
• Four types of phospholipases.
• Phospholipase A1
• Phospholipase A2
• Phospholipase C
• Phospholipase D
20. • 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.
21.
22. • 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.
23. • 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.
24. • 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.
25. • It is responsible for the reverse cholesterol
transport mediated by HDL
• HDL is a good cholesterol.
Lecithin + Cholesterol Lysolecithin + Cholesterol ester
LCAT
26. • Sphingomyelinase of lysosomes hydrolyses
sphingomyelins to ceramide & phosphoryl
choline.
• Ceramide is further degraded to sphingosine &
free fatty acid.
Ceramide
(sphingosine - FFA)
Phosphoryl choline
Sphingomyelinase
Ceramidase
Action of sphingomyelinase &
ceramidase on sphingomyelin
27. • 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.
28. • 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