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LIPOPROTEINS

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					LIPOPROTEINS
BIOCHEMISTRY
DR AMINA TARIQ
Intestinal Uptake of Lipids

   In order for the body to make use of
    dietary lipids, they must first be absorbed
    from the small intestine. Since these
    molecules are oils, they are essentially
    insoluble in the aqueous environment of
    the intestine.
   The solubilization (or emulsification) of
    dietary lipids is therefore accomplished by
    means of bile salts, which are synthesized
    from cholesterol in the liver and then
    stored in the gallbladder; they are
    secreted following the ingestion of fat.
   Dietary triacylglycerols and cholesterol, as
    well as triacylglycerols and cholesterol
    synthesized by the liver, are solubilized in
    lipid-protein complexes.
   These complexes contain triacylglycerol
    lipid droplets and cholesteryl esters
    surrounded by the polar phospholipids
    and proteins identified as apolipoproteins.
    These lipid-protein complexes vary in
    their content of lipid and protein.
Transport of Fat: Lipoproteins
I.     Chylomicrons
II.    Triglyceride storage in adipose
III.   VLDL, LDL, IDL, HDL
IV.    Reverse Cholesterol Transport
V.     Medical implications
VI.    Nutritional regulation of lipoproteins
Overview
   Transport dietary lipids from intestine to liver
    (exogenous)

   Transport lipids from liver to peripheral tissues
    (endogenous)

   Lipoproteins
    ◦   Core of TG and CE
    ◦   Surface of phospholipids and some cholesterol
    ◦   Apolipoproteins (regulators of LP metabolism)
    ◦   CM,VLDL, IDL, LDL, HDL
Lipoprotein structure
Lipoproteins
 particles found in plasma that transport
  lipids including cholesterol
 lipoprotein classes
     chylomicrons: take lipids from small intestine
      through lymph cells
     very low density lipoproteins (VLDL)
     intermediate density lipoproteins (IDL)
     low density lipoproteins (LDL)
     high density lipoproteins (HDL)
Table 1. Physical properties and lipid compositions

               CM        VLDL         LDL         HDL

Density
               < 0.94    0.94-1.006   1.006-1.063 1.063-1.210
(g/ml)
Diameter
               6000-2000 600          250         70-120
(Å)

Total lipid
               99        91           80          44
(wt%) *
Triacylglyce
               85        55           10          6
rols
Cholesterol
               3         18           50          40
esters
Cholesterol    2         7            11          7
Phospholipi
               8         20           29          46
ds
.
Lipoprotein    Density        Diameter    Protein % Phosphol   Triacylglycerol
class          (g/mL)         (nm)        of dry wt ipid %     % of dry wt
HDL            1.063-1.21     5 – 15      33        29         8


LDL            1.019 –        18 – 28     25        21         4
               1.063

IDL            1.006-1.019    25 - 50     18        22         31


VLDL           0.95 – 1.006   30 - 80     10        18         50


chylomicrons   < 0.95         100 - 500   1-2       7          84




       Composition and properties of human lipoproteins

most proteins have densities of about 1.3 – 1.4 g/mL and lipid aggregates us
have densities of about 0.8 g/mL
The apolipoproteins
   major components of lipoproteins
   often referred to as aproteins
   classified by alphabetical designation (A thru E)
   the use of roman numeral suffix describes the
    order in which the apolipoprotein emerge from
    a chromatographic column
   responsible for recognition of particle by
    receptors
Apoproteins of human lipoproteins
   A-I (28,300)- principal protein in HDL
       90 –120 mg% in plasma; activates LCAT
   A-II (8,700) – occurs as dimer mainly in HDL
       30 – 50 mg %; enhances hepatic lipase activity
   B-48 (240,000) – found only in chylomicron
    ◦ <5 mg %; derived from apo-B-100 gene by RNA
      editing; lacks the LDL receptor-binding domain of
      apo-B-100
   B-100 (500,000) – principal protein in LDL
       80 –100 mg %; binds to LDL receptor
Apoproteins of human lipoproteins
   C-I (7,000) – found in chylomicron,VLDL, HDL
       4 – 7 mg %; may also activate LCAT
   C-II (8,800) - found in chylomicron,VLDL, HDL
       3 – 8 mg %; activates lipoprotein lipase
   C-III (8,800) - found in chylomicron,VLDL, IDL, HDL
       8 15 mg %; inhibits lipoprotein lipase
   D (32,500) - found in HDL
       8 – 10 mg %; also called cholesterol ester transfer protein (CETP)
   E (34,100) - found in chylomicron,VLDL, IDL HDL
       3 – 6 mg %; binds to LDL receptor
   H (50,000) – found in chylomicron; also known as b-2-
    glycoprotein I (involved in TG metabolism)
LIPOPROTEINS
 spherical particles with a hydrophobic
  core (TG and esterified cholesterol)
 apolipoproteins on the surface
      large: apoB (b-48 and B-100) atherogenic
      smaller: apoA-I, apoC-II, apoE
   classified on the basis of density and
    electrophoretic mobility (VLDL; LDL;
    IDL;HDL; Lp(a)
           Plasma Lipoproteins
           Structure
           figure 19-1

   LP core
    ◦ Triglycerides
    ◦ Cholesterol esters
   LP surface
    ◦ Phospholipids
    ◦ Proteins
    ◦ cholesterol
Exogenous Lipid Transport

 Fatty acids are absorbed by the apical
  microvilli of muscosal cells and resterified
  in the enterocyte (2 monoacylglyercol
  pathway).
 Apo B48 is the structural protein of the
  chylomicron and contain the majority of
  cholesterol (as cholesteryl ester) found in
  chylomicrons.
   Reesterfied TG are added to the
    chylomicron percurors via the action of a TG
    transfer protein.
    Apo B48 is then added. Apo CII is also
    added. This apoliprotein activates LPL
    activity.
   Nascent cylomicrons are assembled in the
    golgi apparatus and released from the
    enterocyte to enter the lymphatic system.
    Eventually chlyomicrons enter the plasma via
    the left thoracic lymph duct.
   Triglycerides and cholesterol esters are
    concentrated in the core of the
    chylomicron.
           Plasma Lipoproteins
           Classes & Functions

 Chylomicrons
 ◦ Synthesized in small intestine
 ◦ Transport dietary lipids
 ◦ 98% lipid, large sized, lowest
   density
 ◦ Apo B-48
    Receptor binding
 ◦ Apo C-II
    Lipoprotein lipase activator
 ◦ Apo E
    Remnant receptor binding
   Chylomicrons are assembled in the
    intestinal mucosa as a means to transport
    dietary cholesterol and triacylglycerols to
    the rest of the body.
   Chylomicrons are, therefore, the
    molecules formed to mobilize dietary
    (exogenous) lipids. The predominant lipids
    of chylomicrons are triacylglycerols.
 TG transfer protein.
 Type 1hyperlipoproteinnemia or
 Familial lipoprotein lipase deficiency
 Hypertriacylglycerolemia.
Chylomicron
 formed through extrusion of resynthesized
  triglycerides from the mucosal cells into the
  intestinal lacteals
 flow through the thoracic ducts into the suclavian
  veins
 degraded to remnants by the action of lipoprotein
  lipase (LpL) which is located on capillary
  endothelial cell surface
 remnants are taken up by liver parenchymal cells
  due to apoE-III and apoE-IV isoform recognition
  sites
Chylomicron
metabolism
   In the capillaries of adipose tissue and
    muscle, the fatty acids of chylomicrons are
    removed from the triacylglycerols by the
    action of lipoprotein lipase (LPL), which is
    found on the surface of the endothelial
    cells of the capillaries. The apoC-II in the
    chylomicrons activates LPL in the
    presence of phospholipid.
   The free fatty acids are then absorbed by
    the tissues and the glycerol backbone of
    the triacylglycerols is returned, via the
    blood, to the liver and kidneys. Glycerol is
    converted to the glycolytic intermediate
    dihydroxyacetone phosphate (DHAP).
   During the removal of fatty acids, a
    substantial portion of phospholipid, apoA
    and apoC is transferred to HDLs. The loss
    of apoC-II prevents LPL from further
    degrading the chylomicron remnants.
   Chylomicron remnants, containing
    primarily cholesteryl esters, apoE and
    apoB-48, are then delivered to, and taken
    up by, the liver through interaction with
    the LDL receptor which requires apoE or
    via the chylomicron remnant receptor.
 The recognition of chylomicron remnants
  by the hepatic remnant receptor also
  requires apoE.
 Chylomicrons function to deliver dietary
  triacylglycerols to adipose tissue and
  muscle and dietary cholesterol to the
  liver.

				
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