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Metabolism of phospholipids
1. Metabolism of Phospholipids
R. C. Gupta
Professor and Head
Department of Biochemistry
National Institute of Medical Sciences
Jaipur, India
2. Phospholipids include: (i) glycerophospho-
lipids and (ii) sphingophospholipids
In glycerophospholipids, the alcohol is
glycerol
In sphingophospholipids, the alcohol is
sphingosine
3.
4.
5. The important glycero-
phospholipids are:
Phosphatidyl choline
Phosphatidyl ethanolamine
Phosphatidyl inositol
Phosphatidyl serine
Diphosphatidyl glycerol
Plasmalogen
6. Phosphatidyl choline is also known as
lecithin
Phosphatidyl ethanolamine is also known
as cephalin
Diphosphatidyl glycerol is also known as
cardiolipin
7. The only phosphosphingolipid is sphingo-
myelin
Sphingomyelin is found predominantly in
myelin sheath
Cell body Node of Ranvier
Schwann cell
Myelin sheathNucleus
8.
9. Amphipathic lipids can form bilayers
since non-polar tails attract each other
Lipid bilayers constitute the basic
structure of membranes
10. Lecithin is synthesized from activated
choline and diacylglycerol
Activated form of choline is CDP-choline
Synthesis of lecithin
11. A phosphate group is transferred from
ATP to choline forming phosphocholine
A cytidyl group is transferred from CTP to
phosphocholine forming CDP-choline
Phosphocholine is transferred from CDP-
choline to diacylglycerol forming lecithin
12.
13. Synthetic pathway for cephalin is similar
to that for lecithin
Ethanolamine is activated to CDP-
ethanolamine
This reacts with diacylglycerol to form
cephalin
Synthesis of cephalin
14.
15. Phosphatidyl serine is synthesized from
CDP-diacylglycerol and serine
CDP-Diacylglycerol is formed from
phosphatidic acid
CDP-Diacylglycerol reacts with serine to
form phosphatidyl serine
Synthesis of phosphatidyl serine
16.
17. Phosphatidyl inositol is synthesized from
CDP-diacylglycerol and inositol
CDP-Diacylglycerol is formed from
phosphatidic acid
CDP-Diacylglycerol reacts with inositol to
form phosphatidyl inositol
Synthesis of phosphatidyl inositol
18.
19. Glycerophospholipids can undergo inter-
conversion
Serine residue of phosphatidyl serine can
be decarboxylated to ethanolamine
This converts phosphatidyl serine into
phosphatidyl ethanolamine
20.
21. Ethanolamine residue of phosphatidyl
ethanolamine can be methylated
Addition of three methyl groups converts
ethanolamine into choline
Thus, phosphatidyl choline can be
formed from phosphatidyl ethanolamine
22.
23. The glycerophospholipids generally have:
A saturated fatty acid
at position 1
An unsaturated fatty
acid at position 2
The fatty acids at position 1 and position 2
are in a continuous state of flux
24. Dipalmitoyl lecithin has palmitate at both
position 1 and position 2
Dipalmitoyl lecithin is a component of
lung surfactant
Lung surfactant lowers surface tension at
the air/liquid interface in the alveoli
25.
26. Cardiolipin is diphosphatidyl glycerol
It is found only in mitochondria where it is
synthesized from:
Two molecules of
CDP-diacylglycerol
One molecule of
glycerol-3-phosphate
Synthesis of cardiolipin
27. A phosphatidate group is transferred from
CDP-diacylglycerol to glycerol-3-phosphate
The product is phosphatidyl glycerol-3-
phosphate
The phosphate group is split off to form
phosphatidyl glycerol
28. Phosphatidyl glycerol reacts with another
molecule of CDP-diacylglycerol
A phosphatidate group is transferred from
CDP-diacylglycerol to phosphatidyl glycerol
The product is diphosphatidyl glycerol
(cardiolipin)
29. CH – O2 – C – R1
O
||
CH – O – C – R2
|
CH – O – CDP2
O
||
CDP-Diacyl-
glycerol
CH –OH
|
CH
2
– OH
|
CH – O – P2
CMP
CH – O2 – C – R1
O
||
CH – O – C – R2
|
CH – O – P –O – CH2 2
|
CH – OH
|
CH – O – P2
O
||
Phosphatidyl glycerol-3-phosphateGlycerol-3-
phosphate
H O2
Pi
CH – O2 – C – R1
O
||
O
||
CH – O – C – R2
|
CH – O – P –O – CH2 2
|
CH – OH
|
CH – OH2
Phosphatidyl glycerol
CH – O2 – C – R3
O
||
CH – O – C – R4
|
CH – O – CDP2
O
||
CDP-Diacyl-
glycerol
CH – O2 – C – R1
O
||
CH – O – C – R2
CH – O – C – R
|
4
CH – O – C – R3
|
|
CH – OH
|
O
||
O
||
O
||
CH – O – P – O – CH2 2
CH – O – P – O – CH2 2
CMP
Diphosphatidyl glycerol (cardiolipin)
31. At first, a fatty acyl group is added to C1
of dihydroxyacetone phosphate (DHAP)
Then, the acyl group is replaced by an
alkyl group
1-Alkyl DHAP is then reduced to 1-alkyl
glycerol-3-phosphate
32.
33. An acyl group is added to C2 of 1-alkyl
glycerol-3-phosphate
The phosphate is removed from C3
Phosphoethanolamine is added to C3
37. In some plasmalogens, ethanolamine is
replaced by choline or serine
Ethanolamine plasmalogen is present in
myelin
Choline plasmalogen is abundant in
cardiac tissue
Serine plasmalogen is present in retina
and white matter
38. Platelet activating factor (PAF) is a
specific type of plasmalogen
It has an alkyl group (generally 16-
carbon) at position 1
The acyl group at position 2 is acetate
Phosphocholine is present at position 3
39.
40. PAF is released by several types of cells
in response to a variety of stimuli
It is a very powerful chemical mediator
It mediates inflammatory reaction, hyper-
sensitivity and anaphylactic shock
PAF causes platelet aggregation, vaso-
dilatation and bronchoconstriction
41. Glycerophospholipids are hydrolysed by
phospholipases
There are several different phospho-
lipases
Each phospholipase acts on a specific
bond
Catabolism of glycerophospholipids
43. Phospholipase A1 hydrolyses the ester
bond at position 1 of phospholipid
Phospholipase A2 hydrolyses the ester
bond at position 2 of phospholipid
Phospholipase A2 converts the phospho-
lipid into a lysophospholipid
44. Phospholipase B acts on lysophospho-
lipid
It removes the fatty acid from position 1
of the lysophospholipid
45.
46. The action of phospholipase A2 on
membrane phospholipids is important in
eicosanoid metabolism
The fatty acid at position 2 is usually a
polyunsaturated fatty acid
The liberated fatty acid is generally used
for eicosanoid synthesis
47. Phospholipase C hydrolyses the ester
bond between phosphate and glycerol
Phospholipase D hydrolyses the bond
between phosphate and nitrogenous base
The partially hydrolysed products can be
reused for synthesis of new phospholipids
48.
49. Sphingomyelin is synthesized from
ceramide and phosphatidyl choline
Ceramide is acyl sphingosine
Synthesis of sphingomyelin
50.
51. Sphingomyelin is catabolized by lyso-
somal sphingomyelinase
Sphingomyelin is hydrolysed into ceramide
and phosphoryl choline
Catabolism of sphingomyelin
52.
53. Fatty liver is a condition in which large
amounts of fat accumulate in the liver
This can later lead to serious disease
Some phospholipids have a role in
prevention of fatty liver
Lipotropic factors and fatty liver
54. Liver is the site for several pathways of
lipid metabolism
Most of the major lipids can be synthe-
sized and catabolized in the liver
Triglycerides are synthesized in liver, and
are transported out of liver as VLDL
55. Lipotropic factors are the compounds
required for transport of lipids out of liver
The lipotropic factors are choline,
methionine and betaine
Their deficiency causes abnormal
accumulation of triglycerides in liver
56. Normally, triglyceride content of liver is
not more than 5% of liver weight
When it exceeds 5%, the condition is
known as fatty liver
Excessive fat deposition in liver may
cause inflammation of liver cells
57. Inflammation of liver cells may lead to
their destruction
This may be followed by formation of
scar tissue in liver (fibrosis)
Extensive replacement of liver cells by
fibrous tissue results in cirrhosis of liver
58. Fatty liver:
Fat more
than 5%
Fibrosis:
Formation of
scar tissue
Cirrhosis:
Hardening of
liver tissue
Normal liver:
Fat less
than 5%
59. Fatty liver may be caused by:
Obesity
Diabetes mellitus
Severe protein deficiency
Deficiency of essential fatty acids
Hepatotoxic chemicals and drugs
60. Chronic alcoholism is the most important
cause of fatty liver and cirrhosis of liver
With a calorific value is 7 kcal/gm,
alcohol (ethanol) is rich in energy
After ingestion of alcohol, oxidation of
glucose and fatty acids decreases
Alcohol becomes the preferred source of
energy
61. Since fatty acids are not oxidized, they are
esterified with glycerol to form triglycerides
Increased synthesis of triglycerides in liver
leads to their accumulation in liver
This causes fatty liver (specially when
lipotropic factors are deficient)
62. Mechanisms by which
fatty liver is caused are:
Interference in phospholipid synthesis
Disruption of intracellular membranes
Interference in the synthesis of VLDL
Interference in the release of VLDL
63. Choline acts as a lipotropic factor as it is
required to form lecithin
Lecithin is a component of lipoproteins
that help in transport of lipids from liver
Lecithin is also the major component of
membranes
64. Lecithin deficiency may disrupt endo-
plasmic reticulum membrane
Apoprotein component of lipoproteins is
synthesized on endoplasmic reticulum
Disruption of membranes can disturb
VLDL synthesis in liver
65. Betaine and methionine act as lipotropic
factors indirectly
They provide methyl groups for the
synthesis of choline
66. Essential fatty acids also help in the
transport of lipids
They are required for the synthesis of
phospholipids
Fatty acid at C2 of glycerophospholipids
is usually an essential fatty acid