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Classification of Phospholipids
Phospholipids are classified according to alcohol content into:
Glycerophospholipids and Sphingophospholipids
1- Glycerophospholipids: alcohol is glycerol
Glycerophospholipids composed of Glycerol, Two fatty acids,
Phosphate group and Alcohol amine
2- Sphingophospholipids: alcohol is sphingosine
Sphingophospholipids composed of sphingosine alcohol + ONE
Fatty acid + phosphate + Choline
I- Glycerophospholipids
OR
The most common glycerophospholipids are:
1- Phosphatidic acid:
it is the simplest phosphlipid and doesn’t have specific functions
2- Lecithin: It is formed of glycerol, two fatty acids, phosphate and
choline which is a nitrogenous base. It is phosphatidic acid +
choline so it is called phosphatidylcholine
Lecithin
Phosphatidic acid
3- Phosphatidyl ethanolamine (Cephalin): its chemical structure is
exactly as lecithin but choline is replaced by ethanolamine
4- Phosphatidyl serine
Phosphatidyl Serine is an important
phospholipid which supports cell
integrity
- Found in high concentrations in
the brain, levels of which decline
with age.
- It is essential for normal neuron
structure and function and may play
a critical role in maintaining
concentration and memory
5- Phosphatidyl inositol:
It is one of cell
membrane lipids
(but less common)
In addition it plays a
role in cell
signaling (a group of
events that lead to
specific cellular
response)
How do lipids
behave in an
aqueous
environment?
Phospholipids are
amphipathic
molecules. They
aggregate to hide
their hydrophobic
tail inside and
expose
hydrophilic head
to the
outside.
Synthesis of glycerophospholipids: Liver is the site of synthesis
(A) Synthesis of lecithin (phosphatidyl choline) and cephalin
(phosphatidyl ethanolamine):
Their synthesis needs
1- Glycerol activated by ATP (by glycerol kinase) giving glycerol3-phosphate
2-
Two fatty acids activated by CoA (by thiokinase) giving acyl
CoA (active FA).
3- Choline (for synthesis of lecithin) or ethanolamine (for synthesis
of cephalines) activated by CTP to give CDP choline or CDP
ethanolamine.
Synthesis of Lecithin
Lecithin
A)
CH2-OH
CH-OH
B)
CH 2-OH
2 RCOOH
Glycerol
Fatty acid
ATP
Lecithicin
glycerokinase
2 CoASH
ADP
thiokinase
CH2-OH
CH-OH
O
2 RC-SCoA
CH 2-O-PO 3
Acyl CoA
3-glycerophosphate
- 2CoA
CDP -choline
CH2O-CO-R1
CH2-O-CO-R1
C)
Phosphatase
CH-O-CO-R2
CH 2-O-PO 3
CH 2O-CH 3O-R 2
pi
CH 2-O-H
1,2 diacylglycerol (DAG)
Phosphatidic acid
B) Synthesis of phosphatidyl serine:
Phosphatidylserine is formed when phosphatidylethanolamine
reacts with serine, which replaces the ethanolamine moiety
Degradation of glycerophospholipids
Degradation of phospholipids:
Phospholipase A1
CH 2OH
CH2O-COR1
R 1COOH
Phospholipase A2
CHOCOR2
CHO-COR 2
CH2O-P-O-X
CH 2O-P-O- X
Lysolecithin
or
lysocephaline
O
O
R 2COOH
CH 2OH
Free glycerol + P + base
CHOH
Phospholipase C (phosphdiesterase)
CH 2O -P-O- X
Phosphlipase D
(phosphatase)
•Phospholipase A1: Act on ester bond in position 1: removes the
first fatty acid from lecithin or cephalin producing lysolecithin or
lysocephalin.
•Phospholipase A2 (PLA2)): act on position 2 removes the second
fatty acid from lysolecithin or lysocephalin.
•Phospholipase C (phosphodiesterase): act on linkage between
the glycerol and phosphate giving free glycerol and
phosphate+base (phosphoryl base)
•Phospholipase D (phosphatase): act on linkage between
phosphate and base giving free phosphate and free base.
Importance of PLA2
When PLA2 act on membrane phospholipids, it releases arachidonic
acid from C2 of glycerol. Arachidonic acid enter in synthesis of
prostaglandins and leukotriens which causes inflammation. The
pathway is catalyzed by cycloxygenase enzyme (COX). This enzyme
can be inhibited by aspirin. Cortison can inhibit PLA2
PLA2 are commonly found in mammalian tissues as well as insect
and snake venom. Due to the increased presence and activity of
PLA2 resulting from a snake or insect bite, aracidonic acid is
released from the phospholipid membrane . As a result, inflammation
and pain occur at the site of insect bite.
NSAIDs (means non steroidal anti-inflammtory
drugs e.g. aspirin) inhibits cycloxygenase
(COX). While, cortison inhibits PLA2.
Importance of phospholipase C (PLC):
When PLC act on phosphatidyl inositol 4,5 biphosphate, it
release inositol triphosphate (IP3) and DAG which are important
second messengers
Functions of phospholipids:
1- Enter in the structure of cell membranes
2- Component of lipoproteins.
3- Blood clotting: Cephalins
enter in the formation of
thromboplastin which is necessary for blood clotting.
4- Phospholipids as a component of bile in bile make cholesterol
soluble. Their deficiency leads to cholesterol gallstones (see image
A).
5- Dipalmitoyl lecithin act as lung surfactant, prevent alveolar
collapse and allow air passage (see image B).
Respiratory distress syndrome in the newborn:
Lung surfactant is the extracellular fluid layer lining the alveoli.
Surfactants serve to decrease the surface tension of this fluid layer,
reducing the presure needed to reinflate alveoli and prevent alveolar
collapse.
Dipalmitoylphosphatidylcholine (DPPC) or called (dipalmitoyl
lecithin, DPL) serves as the major component of lung surfactant in
adults, allowing the lungs to function normally.
This phospholipid develops in the fetus after 30 weeks of
gestation.
Premature (preterm) infants do not have an adequate amount of this
phospholipid. As a result, acute respiratory distress syndrome can
occur and associated with insufficient surfactant and cause neonatal
death.
Image A) Choleserol gallstones
Phospholipid bilayer
Image B: alveolar collapse in absence of surfactant
(dipalmitoyl lecithin)
2-Sphingophospholipids
Sphingomyelin: it is a sphingophospholipid
Not contain glycerol but contain alcohol called : sphingosine,
Fatty acid is attached to amino group of sphingosine and
phosphorylcholine (phosphate + choline) is attached to the last
OH group.
Sources: present in high amount in brain and nerve tissues.
Synthesis of sphingomyelins:
Sphingomyelin is formed of sphingosine base, fatty acyl CoA,
phosphate and choline.
Steps of synthesis:
1- Palmitic acid is activated by CoA to give palmitoyl CoA.
2- Combination of palmitoyl CoA with serine to form sphingosine
derivative
(ketosphinganine)
which
after
modification
gives
sphingosine base.
3- Then sphingosine reacts with acyl CoA to form ceramide
4- Ceramide then reacts with lecithin (phosphatidyl choline) to form
sphingomyelin and diacylglycerol.
CH3(CH2)12CH 2CH2 C-CoA + OH- CH2-CH
O
NH2
COOH
Serine
Pamitoyl CoA
CO2
CoA
CH3(CH2)12CH 2CH2C-CH- CH2-OH
O
Ketosphinganine
NH 2
1- reduction of keto group into CHOH,
2- o xidatio n of CH CH into CH=CH
2
2
CH 3(CH 2) 12CH=CHCH
HO
CH-CH2-OH
Sphingosine
NH 2
RC- CoA
acyl CoA
O
CH3(CH 2)12CH=CHCH
HO
CH-CH 2- OH
Ceramide
HNC=O
R
Phosphatidyl choline
OH
Sphingomyelin
CH 3(CH 2)12CH=CHCH
HO
CH-CH2-O-P-O-CH2CH2 N(CH3)3
HNC=O
O
Degradation of sphingomyelin:
by sphingomyelinase enzyme in lysosome
giving ceramide and phosphatidyl choline
Niemann-Pick disease: in children
Niemann-Pick disease results from genetic absence of
sphingomyelinase enzyme (the enzyme that breakdown
excess sphingomylein). The absence of this enzyme
leads to accumulation of sphingomyelin in liver and
spleen leading to enlargement of these organs and may
cause reduced appetite, abdominal distension and pain,
and the enlarged spleen may trap platelets and other
blood cells, leading to reduced numbers of these cells in
the circulation. The disease is fatal in early life.
Sphingomyelin accumulation in the brain results in
unsteady gait (ataxia), slurring of speech and difficult
swallowing (dysphagia). More widespread disease
involving the cerebral cortex cause dementia and
seizers.