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6/9/2014 7:39:25 AM 1uploaded by elhadi hassan
By
Dr. Elrasheed Eltaher Osman
6/9/2014 7:39:25 AM 2uploaded by elhadi hassan
 Dietary lipids and de novo synthesized lipid
by adipose tissue and liver must be
transported between various tissues and
organs for utilization and storage.
 Lipids are insoluble in water
 The problem arises of how to transport
this non-polar molecules in aqueous
environment (the blood)
6/9/2014 7:39:25 AM 3uploaded by elhadi hassan
The problem solved through
transporters called lipoproteins
They are amphipathic molecules
(two phases polar and non-polar)
6/9/2014 7:39:25 AM 4uploaded by elhadi hassan
 Definition
 Classes
 Components
 The apolipoproteins
 Description of each class
 Metabolism
6/9/2014 7:39:25 AM 5uploaded by elhadi hassan
These are complex lipids containing
protein that transport lipid in the
blood
They are amphipathic molecule
6/9/2014 7:39:25 AM 6uploaded by elhadi hassan
Classify according to density into
1- chylomicron
2- very low density lipoprotein
(VLDL)
3- low density lipoprotein (LDL)
4- high density lipoprotein (HDL)
6/9/2014 7:39:25 AM 7uploaded by elhadi hassan
Classify according to movement
in eletrophoresis into
1- preβ-lipoprotein
2- β-lipoprotein
3- α-lipoprotein
6/9/2014 7:39:25 AM 8uploaded by elhadi hassan
Consist of
1- lipids
2- proteins
6/9/2014 7:39:25 AM 9uploaded by elhadi hassan
6/9/2014 7:39:25 AM 10uploaded by elhadi hassan
6/9/2014 7:39:25 AM 11uploaded by elhadi hassan
 This consist of
1- phospholipids
2- cholesterol
3- triacylglycerol
4- cholesteroylester
 The 2 above make outer membrane
 The 2 below found inside making the
core
6/9/2014 7:39:25 AM 12uploaded by elhadi hassan
6/9/2014 7:39:25 AM 13uploaded by elhadi hassan
Called apolipoproteins
They are either integral part or
freely exchangeable proteins
Nomenclature :using the letters A,
B, C, D, and E
Sub classes represent by latin
number I, II, III and IV example
apo A I, II, III, and IV apo C I, II and
III
Apo B are two B100 and B48 (only
48% of the length of the first)
6/9/2014 7:39:25 AM 14uploaded by elhadi hassan
Structural function apoB
Receptor ligand apo E
Enzyme activator apo A-I
Enzyme inhibitor apo A-II
Transporter apo D (lipid transfer
protein)
6/9/2014 7:39:25 AM 15uploaded by elhadi hassan
 Include
1- Apo B100
2- Apo B48
3- Apo A- I.II.III and IV
4- Apo C- I.II and III
5- Apo E
6- Apo D
6/9/2014 7:39:25 AM 16uploaded by elhadi hassan
 Is the of longest polypeptide (4536 aa)
 Is glycoprotein
 Synthesize in the liver
 Found in VLDL, IDL and LDL
 Integral protein play structural role as
well as receptor ligand for LDL receptor
6/9/2014 7:39:25 AM 17uploaded by elhadi hassan
 Is about 48 % of the length of Apo B100
Contain 2153 amino acids
Synthesized by intestine
Play structural role in chylomicron
6/9/2014 7:39:25 AM 18uploaded by elhadi hassan
Four types I, II, III and IV
Found in HDL exchange with other
LPs (chylomicrons)
Apo A-I is activator of enzyme LCAT
and ligand for HDL receptor
Apo A-II is two identical polypeptides
joint by disulfide bridge inhibitor of
Apo A-I and LCAT
Apo A-IV associated with formation of
triacylglycerol –riched LP
(chylomicron)
6/9/2014 7:39:25 AM 19uploaded by elhadi hassan
 Three types Apo C-I, II and III
 Small polypeptides freely transferable
between the different LPs
 Apo C-I found in VLDL, HDL and
chylomicron and is possiblr activator of
LCAT
Apo C-II found in VLDL, HDL and
chylomicron and is activator of
lipoprotein lipase
Apo C-III found in VLDL, HDL and
chylomicron and is polymophous (due
to sialic acid content) inhibitor of Apo
C-II
6/9/2014 7:39:25 AM 20uploaded by elhadi hassan
 Found in VLDL, IDL, LDL, chylomircon
and chylomicron reminants
 Integral protein
 Is a ligand for chylomicron reminant
receptor in liver and LDL receptor in
extra-hepatic tissue
6/9/2014 7:39:25 AM 21uploaded by elhadi hassan
 Is the large in size lest in density LPs
 Synthesized by intestine
 Carried the dietary lipid (triacylglycerol
and cholesterol)
 About 88% is triacylglycerol
 Contains Apo B48, Apo A (I,II) and Apo C
6/9/2014 7:39:25 AM 22uploaded by elhadi hassan
Found in certain HDL subfraction
May act as transporter
Called lipid transfer protein
6/9/2014 7:39:25 AM 23uploaded by elhadi hassan
6/9/2014 7:39:25 AM 24uploaded by elhadi hassan
Chylomicrom
Very low density lipoprotein (VLDL)
Low density lipoprotein (LDL)
High density lipoprotein (HDL)
6/9/2014 7:39:25 AM 25uploaded by elhadi hassan
Lymph Enterocyte
Intestinal
Lumen
With
apoB48 Cholesteryl
Ester
Triglyceride
Phospholipid
6/9/2014 7:39:25 AM 26uploaded by elhadi hassan
 Secret in lymph goes to extrahepatic tissue
(mainly adipose tissue)first where are
metabolized
 Metabolized by lipoprotein lipase to free
fastty acid and chylomiron reminants
 The chylomicron reminant goes to the liver
where further metabolism occur
 The chylomicron reminant entr the liver
through receptor mediated pinocytosis
6/9/2014 7:39:25 AM 27uploaded by elhadi hassan
Enzyme hydrolyzed tracylglycerol
ninto fatty acids and glycerol
Found in blood vessels near extra-
hepatic tissue mainly adipose tissue,
heart and muscle
It is partculate enzyme anchored to
endothelium by( –ve proteoplycan
chain of heparan sulfate),bond
that is released by administration
of heparin
6/9/2014 7:39:25 AM 28uploaded by elhadi hassan
 Synthesized and secreted by liver
 Carries lipid synthesized inside the liver
 Carried about 60 % triacylglycerol
 Contain Apo B100, Apo C and Apo E
 Metabolyzed by lipoprotein lipase into
intermediate density lipoprotein IDL and
LDL
6/9/2014 7:39:25 AM 29uploaded by elhadi hassan
6/9/2014 7:39:25 AM 30uploaded by elhadi hassan
Synthesized in the blood from other
LPs mainly VLDL
Carried cholesterol to extra-hepatic
tissue
Responsible for high blood
cholesterol (bad cholesterol)
Contain Apo B100 and Apo E
Most of LDL degraded in liver
through Apo B100 and E receptors
A positive correlation exist between
incidence of coronary
atherosclerosis and plasma
concentration of LDL
6/9/2014 7:39:25 AM 31uploaded by elhadi hassan
 Is synthesized and secreted from both liver
and intestine
 Contains Apo A, C and E
 Nascent HDL from intestine lack Apo C and E
gain them when enter the blood from hepatic
HDL
 HDL act as repository for Apo C and E that
required for metabolism of VLDL and
chylomicrons
6/9/2014 7:39:25 AM 32uploaded by elhadi hassan
 The nascent HDL consists of discoid PL bi-
layers containing Apo A and free cholesterol
 When joins the enzyme LCAT
(lecithin,cholesterol :acyltransferase) the free
cholesterol esterified by one fatty of the PLs
to form cholesteroylester and
lysophospholipid
 Cholesteroylester in non-polar moves to
hydrophobic interior of the bi-layer where
lysolecithin is transferred to plasma albumin
6/9/2014 7:39:25 AM 33uploaded by elhadi hassan
 LCAT continues forming CE that migrates
to interior forming non-polar core the
HDL become spherical in shape
 LCAT system remove the unesterified
cholesterol from lipoprotein and from
tissue
 HDL cycle account for transporting
cholesterol from tissue to liver (good
cholesterol) n process called reverse
cholesterol transport
6/9/2014 7:39:25 AM 34uploaded by elhadi hassan
6/9/2014 7:39:25 AM 35uploaded by elhadi hassan
6/9/2014 7:39:25 AM 36uploaded by elhadi hassan

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Lipids transport

  • 1. 6/9/2014 7:39:25 AM 1uploaded by elhadi hassan
  • 2. By Dr. Elrasheed Eltaher Osman 6/9/2014 7:39:25 AM 2uploaded by elhadi hassan
  • 3.  Dietary lipids and de novo synthesized lipid by adipose tissue and liver must be transported between various tissues and organs for utilization and storage.  Lipids are insoluble in water  The problem arises of how to transport this non-polar molecules in aqueous environment (the blood) 6/9/2014 7:39:25 AM 3uploaded by elhadi hassan
  • 4. The problem solved through transporters called lipoproteins They are amphipathic molecules (two phases polar and non-polar) 6/9/2014 7:39:25 AM 4uploaded by elhadi hassan
  • 5.  Definition  Classes  Components  The apolipoproteins  Description of each class  Metabolism 6/9/2014 7:39:25 AM 5uploaded by elhadi hassan
  • 6. These are complex lipids containing protein that transport lipid in the blood They are amphipathic molecule 6/9/2014 7:39:25 AM 6uploaded by elhadi hassan
  • 7. Classify according to density into 1- chylomicron 2- very low density lipoprotein (VLDL) 3- low density lipoprotein (LDL) 4- high density lipoprotein (HDL) 6/9/2014 7:39:25 AM 7uploaded by elhadi hassan
  • 8. Classify according to movement in eletrophoresis into 1- preβ-lipoprotein 2- β-lipoprotein 3- α-lipoprotein 6/9/2014 7:39:25 AM 8uploaded by elhadi hassan
  • 9. Consist of 1- lipids 2- proteins 6/9/2014 7:39:25 AM 9uploaded by elhadi hassan
  • 10. 6/9/2014 7:39:25 AM 10uploaded by elhadi hassan
  • 11. 6/9/2014 7:39:25 AM 11uploaded by elhadi hassan
  • 12.  This consist of 1- phospholipids 2- cholesterol 3- triacylglycerol 4- cholesteroylester  The 2 above make outer membrane  The 2 below found inside making the core 6/9/2014 7:39:25 AM 12uploaded by elhadi hassan
  • 13. 6/9/2014 7:39:25 AM 13uploaded by elhadi hassan
  • 14. Called apolipoproteins They are either integral part or freely exchangeable proteins Nomenclature :using the letters A, B, C, D, and E Sub classes represent by latin number I, II, III and IV example apo A I, II, III, and IV apo C I, II and III Apo B are two B100 and B48 (only 48% of the length of the first) 6/9/2014 7:39:25 AM 14uploaded by elhadi hassan
  • 15. Structural function apoB Receptor ligand apo E Enzyme activator apo A-I Enzyme inhibitor apo A-II Transporter apo D (lipid transfer protein) 6/9/2014 7:39:25 AM 15uploaded by elhadi hassan
  • 16.  Include 1- Apo B100 2- Apo B48 3- Apo A- I.II.III and IV 4- Apo C- I.II and III 5- Apo E 6- Apo D 6/9/2014 7:39:25 AM 16uploaded by elhadi hassan
  • 17.  Is the of longest polypeptide (4536 aa)  Is glycoprotein  Synthesize in the liver  Found in VLDL, IDL and LDL  Integral protein play structural role as well as receptor ligand for LDL receptor 6/9/2014 7:39:25 AM 17uploaded by elhadi hassan
  • 18.  Is about 48 % of the length of Apo B100 Contain 2153 amino acids Synthesized by intestine Play structural role in chylomicron 6/9/2014 7:39:25 AM 18uploaded by elhadi hassan
  • 19. Four types I, II, III and IV Found in HDL exchange with other LPs (chylomicrons) Apo A-I is activator of enzyme LCAT and ligand for HDL receptor Apo A-II is two identical polypeptides joint by disulfide bridge inhibitor of Apo A-I and LCAT Apo A-IV associated with formation of triacylglycerol –riched LP (chylomicron) 6/9/2014 7:39:25 AM 19uploaded by elhadi hassan
  • 20.  Three types Apo C-I, II and III  Small polypeptides freely transferable between the different LPs  Apo C-I found in VLDL, HDL and chylomicron and is possiblr activator of LCAT Apo C-II found in VLDL, HDL and chylomicron and is activator of lipoprotein lipase Apo C-III found in VLDL, HDL and chylomicron and is polymophous (due to sialic acid content) inhibitor of Apo C-II 6/9/2014 7:39:25 AM 20uploaded by elhadi hassan
  • 21.  Found in VLDL, IDL, LDL, chylomircon and chylomicron reminants  Integral protein  Is a ligand for chylomicron reminant receptor in liver and LDL receptor in extra-hepatic tissue 6/9/2014 7:39:25 AM 21uploaded by elhadi hassan
  • 22.  Is the large in size lest in density LPs  Synthesized by intestine  Carried the dietary lipid (triacylglycerol and cholesterol)  About 88% is triacylglycerol  Contains Apo B48, Apo A (I,II) and Apo C 6/9/2014 7:39:25 AM 22uploaded by elhadi hassan
  • 23. Found in certain HDL subfraction May act as transporter Called lipid transfer protein 6/9/2014 7:39:25 AM 23uploaded by elhadi hassan
  • 24. 6/9/2014 7:39:25 AM 24uploaded by elhadi hassan
  • 25. Chylomicrom Very low density lipoprotein (VLDL) Low density lipoprotein (LDL) High density lipoprotein (HDL) 6/9/2014 7:39:25 AM 25uploaded by elhadi hassan
  • 27.  Secret in lymph goes to extrahepatic tissue (mainly adipose tissue)first where are metabolized  Metabolized by lipoprotein lipase to free fastty acid and chylomiron reminants  The chylomicron reminant goes to the liver where further metabolism occur  The chylomicron reminant entr the liver through receptor mediated pinocytosis 6/9/2014 7:39:25 AM 27uploaded by elhadi hassan
  • 28. Enzyme hydrolyzed tracylglycerol ninto fatty acids and glycerol Found in blood vessels near extra- hepatic tissue mainly adipose tissue, heart and muscle It is partculate enzyme anchored to endothelium by( –ve proteoplycan chain of heparan sulfate),bond that is released by administration of heparin 6/9/2014 7:39:25 AM 28uploaded by elhadi hassan
  • 29.  Synthesized and secreted by liver  Carries lipid synthesized inside the liver  Carried about 60 % triacylglycerol  Contain Apo B100, Apo C and Apo E  Metabolyzed by lipoprotein lipase into intermediate density lipoprotein IDL and LDL 6/9/2014 7:39:25 AM 29uploaded by elhadi hassan
  • 30. 6/9/2014 7:39:25 AM 30uploaded by elhadi hassan
  • 31. Synthesized in the blood from other LPs mainly VLDL Carried cholesterol to extra-hepatic tissue Responsible for high blood cholesterol (bad cholesterol) Contain Apo B100 and Apo E Most of LDL degraded in liver through Apo B100 and E receptors A positive correlation exist between incidence of coronary atherosclerosis and plasma concentration of LDL 6/9/2014 7:39:25 AM 31uploaded by elhadi hassan
  • 32.  Is synthesized and secreted from both liver and intestine  Contains Apo A, C and E  Nascent HDL from intestine lack Apo C and E gain them when enter the blood from hepatic HDL  HDL act as repository for Apo C and E that required for metabolism of VLDL and chylomicrons 6/9/2014 7:39:25 AM 32uploaded by elhadi hassan
  • 33.  The nascent HDL consists of discoid PL bi- layers containing Apo A and free cholesterol  When joins the enzyme LCAT (lecithin,cholesterol :acyltransferase) the free cholesterol esterified by one fatty of the PLs to form cholesteroylester and lysophospholipid  Cholesteroylester in non-polar moves to hydrophobic interior of the bi-layer where lysolecithin is transferred to plasma albumin 6/9/2014 7:39:25 AM 33uploaded by elhadi hassan
  • 34.  LCAT continues forming CE that migrates to interior forming non-polar core the HDL become spherical in shape  LCAT system remove the unesterified cholesterol from lipoprotein and from tissue  HDL cycle account for transporting cholesterol from tissue to liver (good cholesterol) n process called reverse cholesterol transport 6/9/2014 7:39:25 AM 34uploaded by elhadi hassan
  • 35. 6/9/2014 7:39:25 AM 35uploaded by elhadi hassan
  • 36. 6/9/2014 7:39:25 AM 36uploaded by elhadi hassan