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PLASMA LIPOPROTEINS



DR MUHAMMAD MUSTANSAR
Plasma Lipids
Plasma lipids are usually measured after 12 hours
    fasting. The mean value of plasma lipids is 470 mg/dl.
    The different types of Plasma lipids are :
     Triglyceride
         normal range 50 – 150 (mean value 100 mg/dl)
    Cholesterol
         normal range 100– 200(mean value 150 mg/dl)
    Phospholipids
         normal range 150 –250 (mean value 200 mg/dl)
    Free fatty acids
         normal range 10 – 30 (mean value 20 mg/dl)


2
Lipid transport in the circulation
Lipids are insoluble in plasma. In order to be transported they are combined
with specific proteins to form lipoproteins:


                                                 Proteins (apoproteins)


                      HO




                              O                           Non polar lipids in core
Cholesterol
                              R
                                                        (TAG and cholesterol esters)
                                  O

                                  R
                                            HO
                                            H




                     HO




Apoproteins are only weakly associated with a particular lipoprotein and are
easily transferred to another lipoprotein of a different class. Apoproteins have
various functions including:
• Structural role
• Binding sites for receptors
• Activators or co-enzymes for enzymes involved with lipid metabolism
Plasma Lipoproteins
All Lipids in plasma are
 transported in the form
 lipoproteins.
Any lipoprotein has:
     central core: formed of non-
      polar lipids (triglycerids &
      cholesterol esters).
     outer layer: formed of the
      more polar lipids
      (phospholipids & non-
      esterified cholesterol), and
      proteins (apoproteins)

 5
Structure of lipoprotein
                           INTEGRAL APOPROTEINS

                                 MONOLAYER OF
                                 PHOSPHOLIPID
CHOLESTEROL                    AND CHOLESTERLOL
                               CORE
  ESTERS



TRIGLYCERIDES

                           PERIPHERAL APOPROTEINS
Apoproteins
  Are either peripheral (can be transferred) or integral
   (cannot be transferred).
  Function:
      They  act as activator for the enzymes that
       act on lipoproteins
      They are important for receptor recognition
       to uptake the lipoproteins by certain
       tissues.



  7
General Functions of Lipoproteins
    1. Keep lipids soluble as they transport them
       in plasma
    2. Provide an efficient mechanism for
       delivering their lipid content to tissues




8
Plasma lipoproteins can be separated into different
      fractions by two methods, electrophoresis and
      ultracentrifugation.


Ultracentrifugation                                 Electrophoresis

                                          Non-mobile
                   Chylomicrons
                                           fraction
                   VLDL               β-lipoproteins

                   LDL            Pre β- lipoproteins

                    HDL              α - lipoproteins
                      Free FA –Albumin


                                                         (+)

 9
10
The five classes of lipoprotein
                     (all contain characteristic amounts TAG, cholesterol, cholesterol esters,
                     phospholipids and apoproteins)
                                                   Diameter                                Major apoliproteins
                                Class                (nm)        Source and function

                            Chylomicrons             500        Intestine. Transport of     A, B48, C(I,II,III) E
                                (CM)                                 dietary TAG

                           Very low density          43          Liver. Transport of        B100, C(I,II,III) , E
Increasing density




                             lipoproteins                     endogenously synthesised
                                (VLDL)                                   TAG

                       Low density lipoproteins      22       Formed in circulation by             B100
                               (LDL)                          partial breakdown of IDL.
                                                               Delivers cholesterol to
                                                                 peripheral tissues
                       High density lipoproteins      8         Liver. Removes “used”        A, C(I,II,III), D, E
                                (HDL)                          cholesterol from tissues
                                                                  and takes it to liver.
                                                              Donates apolipoproteins to
                                                                     CM and VLDL
&%
                   Types of
Lipoproteins                                Lipid Content                Origin
                  apoprotein
                      s
                      2%         •   TAG 90% (Main lipid)
 Chylomicrons     A, B48, C-II   •   Cholesterol (free & esters) 5%     Intestine
                      &E         •   Phospholipids 3%
    VLDL
                                 •   TAG 60% (Main lipid)
  (very low         % 10
                  B100, C, E
                                 •   Phospholipids 15%                    Liver
   density                       •   Cholesterol ( free & esters)15%
lipoproteins)
      IDL                        • Cholesterol (free & esters)
(intermediate       % 11           45% (Main lipid)                    Breakdown
     density        B100, E      • Phospholipids 25 %                   of VLDL
  lipoproteins)                  • TAG 30 %

                                 • Cholesterol (free & esters)         Breakdown
     LDL
                     20 %          50% (Main lipid)
(low density          B100       • Phospholipids 22 %
                                                                       of VLDL via
 lipoproteins)                   • TAG 8 %                                 IDL
                                 •   Cholesterol (free & esters) 15%
    HDL
                    50 %         •   Phospholipids 30% (Main
(high density                                                             Liver
                   A,C,D,E           lipid)                                   13
Lipoprotein              Functions                    Clinical

                                                    significance

              •Transport dietary TAG               Increased in
Chylomicron   (mainly), cholesterol &              deficiency of
              cholesterol esters from the        lipoprotein lipase
       s
              intestine to the peripheral
               tissues
              •Transport endogenous TAG           Defect in their
      VLDL    from the liver to the peripheral   synthesis leads to
              tissues (Mobilize fat from             fatty liver
               liver)
      LDL     •Transport cholesterol from the     Their increase
              liver to the peripheral tissues         leads to
                                                  atherosclerosis.
              •Remove free cholesterol from       Their decrease
              peripheral tissues & esterifies         leads to
 14   HDL
15
Uptake of LDL & its regulation
 The uptake of LDL occurs mainly in the liver
  (75%), adrenals and adipose tissue.
 LDL are taken up by cells by LDL receptor-
  mediated endocytosis.
 The interaction of LDL with LDL receptors
  requires the presence of apoB100 which is found
  only on LDL).
 The      endocytosed      membrane         vesicles
  (endosomes) fuse with lysosomes, in which the
  apoproteins are degraded and the cholesterol
  esters are hydrolyzed to yield free cholesterol.

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LIPOPROTEINS MUHAMMAD MUSTANSAR FJMC LAHORE

  • 2. Plasma Lipids Plasma lipids are usually measured after 12 hours fasting. The mean value of plasma lipids is 470 mg/dl. The different types of Plasma lipids are : Triglyceride  normal range 50 – 150 (mean value 100 mg/dl) Cholesterol  normal range 100– 200(mean value 150 mg/dl) Phospholipids  normal range 150 –250 (mean value 200 mg/dl) Free fatty acids  normal range 10 – 30 (mean value 20 mg/dl) 2
  • 3.
  • 4. Lipid transport in the circulation Lipids are insoluble in plasma. In order to be transported they are combined with specific proteins to form lipoproteins: Proteins (apoproteins) HO O Non polar lipids in core Cholesterol R (TAG and cholesterol esters) O R HO H HO Apoproteins are only weakly associated with a particular lipoprotein and are easily transferred to another lipoprotein of a different class. Apoproteins have various functions including: • Structural role • Binding sites for receptors • Activators or co-enzymes for enzymes involved with lipid metabolism
  • 5. Plasma Lipoproteins All Lipids in plasma are transported in the form lipoproteins. Any lipoprotein has: central core: formed of non- polar lipids (triglycerids & cholesterol esters). outer layer: formed of the more polar lipids (phospholipids & non- esterified cholesterol), and proteins (apoproteins) 5
  • 6. Structure of lipoprotein INTEGRAL APOPROTEINS MONOLAYER OF PHOSPHOLIPID CHOLESTEROL AND CHOLESTERLOL CORE ESTERS TRIGLYCERIDES PERIPHERAL APOPROTEINS
  • 7. Apoproteins Are either peripheral (can be transferred) or integral (cannot be transferred). Function: They act as activator for the enzymes that act on lipoproteins They are important for receptor recognition to uptake the lipoproteins by certain tissues. 7
  • 8. General Functions of Lipoproteins 1. Keep lipids soluble as they transport them in plasma 2. Provide an efficient mechanism for delivering their lipid content to tissues 8
  • 9. Plasma lipoproteins can be separated into different fractions by two methods, electrophoresis and ultracentrifugation. Ultracentrifugation Electrophoresis Non-mobile Chylomicrons fraction VLDL β-lipoproteins LDL Pre β- lipoproteins HDL α - lipoproteins Free FA –Albumin (+) 9
  • 10. 10
  • 11.
  • 12. The five classes of lipoprotein (all contain characteristic amounts TAG, cholesterol, cholesterol esters, phospholipids and apoproteins) Diameter Major apoliproteins Class (nm) Source and function Chylomicrons 500 Intestine. Transport of A, B48, C(I,II,III) E (CM) dietary TAG Very low density 43 Liver. Transport of B100, C(I,II,III) , E Increasing density lipoproteins endogenously synthesised (VLDL) TAG Low density lipoproteins 22 Formed in circulation by B100 (LDL) partial breakdown of IDL. Delivers cholesterol to peripheral tissues High density lipoproteins 8 Liver. Removes “used” A, C(I,II,III), D, E (HDL) cholesterol from tissues and takes it to liver. Donates apolipoproteins to CM and VLDL
  • 13. &% Types of Lipoproteins Lipid Content Origin apoprotein s 2% • TAG 90% (Main lipid) Chylomicrons A, B48, C-II • Cholesterol (free & esters) 5% Intestine &E • Phospholipids 3% VLDL • TAG 60% (Main lipid) (very low % 10 B100, C, E • Phospholipids 15% Liver density • Cholesterol ( free & esters)15% lipoproteins) IDL • Cholesterol (free & esters) (intermediate % 11 45% (Main lipid) Breakdown density B100, E • Phospholipids 25 % of VLDL lipoproteins) • TAG 30 % • Cholesterol (free & esters) Breakdown LDL 20 % 50% (Main lipid) (low density B100 • Phospholipids 22 % of VLDL via lipoproteins) • TAG 8 % IDL • Cholesterol (free & esters) 15% HDL 50 % • Phospholipids 30% (Main (high density Liver A,C,D,E lipid) 13
  • 14. Lipoprotein Functions Clinical significance •Transport dietary TAG Increased in Chylomicron (mainly), cholesterol & deficiency of cholesterol esters from the lipoprotein lipase s intestine to the peripheral tissues •Transport endogenous TAG Defect in their VLDL from the liver to the peripheral synthesis leads to tissues (Mobilize fat from fatty liver liver) LDL •Transport cholesterol from the Their increase liver to the peripheral tissues leads to atherosclerosis. •Remove free cholesterol from Their decrease peripheral tissues & esterifies leads to 14 HDL
  • 15. 15
  • 16. Uptake of LDL & its regulation  The uptake of LDL occurs mainly in the liver (75%), adrenals and adipose tissue.  LDL are taken up by cells by LDL receptor- mediated endocytosis.  The interaction of LDL with LDL receptors requires the presence of apoB100 which is found only on LDL).  The endocytosed membrane vesicles (endosomes) fuse with lysosomes, in which the apoproteins are degraded and the cholesterol esters are hydrolyzed to yield free cholesterol.