Download Lipids (lect 5, 6))

II- Compound lipids: They composed of fatty acids + alcohol+
other substance which may be phosphorous (phosphlipids), proteins
(lipoproteins), sugar (glycolipid)
(1) Phospholipids
Phospholipids are classified according to alcohol content into:
1- Glycerophospholipids: alcohol is glycerol
2- Sphingophospholipids: alcohol is sphingosine
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
Cephalins: Their chemical structure is exactly as lecithin but they
differ only in the base which may be:
a) Ethanol amine so called: phosphatidyl ethanol amine
b) Serine and so called phosphatidyl serine
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
Phosphatidyl ethanolamine (cephalin)
Sources: brain tissues.
Phosphatidyl inositol: structure not required
It is one of cell
membrane lipids
(but less common)
In addition it plays a
role in cell
signaling
2-Sphingophospholipids
Sphingomyelin: it is a sphingophospholipid
Not contain glycerol but contain alcoholcalled : 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.
Q: Classify each lipid
Phospholipids
Phospholipids are lipids containing phosphate. They also contain alcohol
(glycerol or sphingosine), fatty acids and base (choline, ethanolamine or
serine). See the structures
Sources:
Exogenous: from diet e.g. eggs
Endogenous: In all cell.
Plasma levels: The average total phospholipids are about 200
mg/dl (60% lecithins, 25% cephalins and 15% sphingomyelins)
Digestion and absorption: begins in the intestine
Phospholipids either absorbed as such or are hydrolyzed by certain
pancreatic phospholipases as follow:
•Phospholipase A1: Act on ester bond in position1: 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 producing
glycerophosphoryl
choline
or
glycerophosphoryl ethanolamine, respectively.
•Phospholipase C (phosphodiesterase): act
on linkage between the glycerol and
phosphate giving free glycerol and phosphoryl
choline or phosphoryl ethanolamin.
•Phospholipase D (phosphatase): act on
linkage between phosphate and base giving
free phosphate and free base.
PLA2 releases arachidonic acid from C2 of glycerol.
Arachidonic acid enter in synthesis of prostaglandins and
leukotriens which causes inflammation.
PLA2 are commonly found in mammalian tissues as well as
insect and snake venomDue 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
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)
•If phospholipids absorbed as it is, they are usually absorbed with
triglycerides and cholesterol. All are bound to apoprotein to form
chylomicrons (mainly TG + phospholipids + cholesterol +
apoprotein).
Functions of phospholipids:
1- Enter in the structure of cell membranes
2- Help triglycerides transport (enter in the synthesis of chylomicron) .
3- Blood clotting: Cephalins enter in the formation of thromboplastin
which is necessary for blood clotting.
4- Phospholipids act as lipotropic factors i.e. prevent accumulation of
fats in liver hence prevent fatty liver.
5- Phospholipids in bile make cholesterol soluble. Their deficiency
leads to cholesterol gallstones (see image A).
6- Dipalmitoyl lecithin act as lung surfactant, prevent alveolar collapse
and allow air passage (see image B).
Image A) Choleserol gallstones
Phospholipid bilayer
Image B: alveolar collapse in absence of surfactant
(lecithin)
Synthesis of Phospholipids: Liver is the site of synthesis
(A) Synthesis of lecithin (phosphatidyl choline) and cephalins
(phosphatidyl ethanolamine and phosphatidyl serine):
Their synthesis needs
1-
Glycerol activated by ATP (by glycerokinase) giving 3glycerophosphate.
2- Two fatty acids activated by CoA (by thiokinase) giving acyl
CoA (active FA).
3- Choline (for synthesis of lecithin), ethanolamine or serine (for
synthesis of cephalines) activated by CTP to give CDP choline
or CDP ethanolamine or CDP serine.
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 sphingomyelins:
Sphingomyeline is formed of sphingosine base, fatty acyl CoA, phosphate and
choline. (Remembr structure, first lecture).
Steps of synthesis: see figure
1- Palmitic acid is activated by CoA to give palmitoyl CoA.
2- Combination of palmitoyl CoA with serine to form 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.
Degradation of phospholipids:
- Lecithin and cephalins are degraded by plasma phospholipases A1, A2 , C and
D.(as before).
-Sphigomyelin is degraded by sphingomyleinase
Lecithin (phosphatidyl choline)
Niemann-Pick disease: in children
It is one of lipid storage disease in which harmful
quantities of fatty substances, or lipids, accumulate in the
spleen, liver, lungs, bone marrow, and brain
Niemann-Pick disease results from genetic absence of
sphingomyelinase enzyme leading 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 crortex cause dementia and seizers.
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
CH-CH2-OH
Sphingosine
HO 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
CH3(CH2)12CH=CHCH CH-CH2-O-P-O-CH2CH2 N(CH3)3
HO
HNC=O
O