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Always behave
like a DUCK
Keep calm and unruffled
on the surface
But
Paddle with great vigor underneath
Dr. Dhiraj J. Trivedi
Lipoprotein
and
its Metabolism
What is lipoproteins?
• Lipoproteins are spherical,
macromolecular complexes of lipids and
specific protein called
Apo-protein.
What are the functions of
lipoproteins?
• 1. They keep water insoluble lipids in solution
of aqueous plasma.
• 2. Provide mechanism for transporting their
lipid components to and from the tissue.
What is the general composition
of plasma lipoproteins?
They contain neutral lipid core
made of TG , Cholesteryl esters
and shell of amphipathic
phospholipids,
Unesterified cholesterol
and apoprotein.
HOW ARE THE LIPOPROTEINS
CLASSIFIED?
Classified on the basis of
1.COMPOSITION
2.DENSITY and
3.ELECTRO PHORETIC
MOBILITY
Name the classes of
lipoproteins?
• 1. Chylomicron
• 2. Very low density lipoproteins (VLDL).
• 3. Low density lipoproteins (LDL).
• 4. High density lipoproteins (HDL).
• 5. Free fatty acids – Albumin complex
Arrangement of lipoprotein on
their
Size and Density
Lipoprotein
class
Size Density
Chylomicrone 1000 to 10,000A Less than 0.96
VLDL 300 to 700A Upto 1.006
LDL 150 to 250A Upto 1.063
HDL 75 to 100A Above 1.063
Lipoprotein composition
TG C &
CE
PL Apo
protein
Chylo-
microne
90 % 5 % 3 % 2 %
VLDL 60 % 20 % 15 % 5 %
LDL 08 % 50 % 22 % 20 %
HDL 05 % 25 % 30 % 40 %
Electrophoretic mobilityDensity
Lipoprotein molecule
Write the functions of apolipoproteins.
• 1. Provide recognition sites for cell surface
receptors.
• 2. Serves as coenzymes
• 3. Some are required as a structural part and
can not be replaced or removed.
Write the functions of
CHYLOMICRONES.
• Transport mainly
Exogenous Tri acyl
glycerol from
intestine to Liver,
adipose tissue and
muscle.
• TAG either
absorbed from food
or Synthesized in
enterocytes )
Adipose
Muscle
Write the functions of
Very Low Density Lipoproteins ( VLDL )
• Transports mainly
endogenous Tri acyl
glycerol from Liver to
extra hepatic tissues
• Endogenous Tri acyl
glycerol Synthesized
in hepatocyte
Write the functions of
Low Density Lipoproteins (LDL)
• Transports mainly
Cholesterol and
cholesteryl esters
from Liver to extra
hepatic tissues
cholesterol
Write the functions of
High Density Lipoproteins (HDL)
• Transports mainly
Cholesterol and
Cholesteryl esters
from extra hepatic
tissues to Liver
• Serves to hold apo-
c & apo-e for use
cholesterol
Write the functions of
Free fatty acid Albumin complex
• Transports mainly
free fatty acids
released from
adipose tissue to
Liver for
oxidation
FFA
Adipose
Adipose
Adipose
FFA
FFA
FFA
Enzymes in lipoprotein
metabolism
• Lecithin cholesterol acyl transferase
• L CAT :
• Catalyses transfer of Sn2 FA of phospholipids
to cholesterol.
• Converts polar cholesterol to non polar
cholesteryl esters
• Shift of cholesterol form periphery to core
• Lipoprotein lipase
• Heparin sensitive lipase
Catalyses hydrolysis of chylomicron
and VLDL
Located on capillary surface
Responsible for generating FA and
glycerol in tissue
Enzymes in lipoprotein
metabolism
• Hepatic lipase
Catalyses hydrolysis of TAG and
Phospholipids of HDL and IDL
Located in sinusoid s of liver
Responsible for metabolic degradation
of HDL and IDL
Enzymes in lipoprotein
metabolism
• Acid lipase
• Intracellular lipase
Catalyses hydrolysis of TAG and
cholesteryl esters in lysosomes
Located in lysosome ,
Optimum pH acidic
Responsible for degradation of
lipoprotein taken up by receptor
mediated endocytosis
Enzymes in lipoprotein
metabolism
Lipoprotein
Receptors
E
B10
0
E
Receptor for
chylomicron
remnants
Receptor for
LDL and IDL
X
unknownReceptor for
HDL
Receptor for
LDL does not
recognize VLDL
due to presence
of C ii
Apo C ac t as coenzyme for lipo protein lipase
METABOLISM OF
CHYLOMICRONS
Lipoprotein metabolism
1
Type I
Hyper LP
Lplipase def
Apo Cii def
METABOLISM OF VLDL AND
LDL
Lipoprotein metabolism
2
Type III
Hyper LP
Fatty liver
Type II
Hyper LPLDL not
removed
CELLUAR UPTAKE
AND
DEGRADATION OF LDL
Lipoprotein metabolism
3
Receptor mediated Endocytosis
METABOLISM OF HDL
Lipoprotein metabolism
4
VLD
L
VLD
L
LCAT
Apo – A1
Apo – B
Bad cholesterol
LDL
Good cholesterol
HDL
Lipoproteins and Disease
• Hyperlipoproteinemias and
hypolipoproteinemias are due to
malfunctions in the synthesis and
catabolism of lipoproteins.
HYPERLIPOPROTEINEMIA
TYPE -- I
Deficiency of enzyme lipoprotein
lipase
VLDL and Chylomicrons are not
utilized
High TAG level in the blood
HYPERLIPOPROTEINEMIA
TYPE -- II
Lack of removal of LDL form the blood
Not recognising Apo B100 in LDL receptor
High Cholesterol level in the blood
High risk of CHD and Atherosclerosis
HYPERLIPOPROTEINEMIA
TYPE -- III
Deficiency of enzyme mobilising
VLDL and LDL from circulation
Apo E deficient, impairs uptake
IDL level increase in the blood
HYPERLIPOPROTEINEMIA
TYPE -- IV
Due to imbalance between
synthesis and clearance of VLDL
in circulation
HYPERLIPOPROTEINEMIA
TYPE -- V
Lipoprotein lipase deficient or
utilisation of VLDL and
Chylomicrons
HYPO LIPOPROTEINEMIA
A BETA LIPOPROTEINEMIA
1. Serum LDL and VLDL level
decreased due to absence of Apo B
2. Lack of formation of Chylomicron
after high fatty meal
3. Result malabsorption, steatorrhea
and cholesterol deposition under
skin as nodules
HYPO LIPOPROTEINEMIA – II
Tangier disease
1. Deficiency of Serum HDL due
to absence of Apo A1
2. Result cholesterol ester
deposition in skin , cornea and
blood vessels.
3. Increased risk of premature
CHD
Diseases Genetic defects Risk
LPL defect Reduced level of LPL Pancreatitis
Apo C-11 defect Inability to synthesize
Apo C-11
Pancreatitis
A beta
lipoproteinemia
Inability to synthesize
Apo B
Neurological defect
An alpha
lipoproteinemia
Inability to synthesize
Apo A
Cholesteryl esters
storage in abnormal
sites
Diseases associated with lipoprotein metabolism
Apo B48
Apo A
Intestinal mucosa
Liver
Choesterol
Fatty acid
Apo A
Apo C
Apo E
E
Receptor for
chylomicron
remnants
B48
chylomicron
remnants
B48E
AE
C II
HDL
Ch
PL
Ch
TAG
Ch
TAG
Glycerol
Free FA
Lipoprotein
lipase
C IIE
Nacent
chylomicron
A
E
C II
CM
Ch
PL
B48
A
1
2
3
4
Thank you

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Lipoprotein metabolism

  • 1. Always behave like a DUCK Keep calm and unruffled on the surface But Paddle with great vigor underneath Dr. Dhiraj J. Trivedi
  • 3. What is lipoproteins? • Lipoproteins are spherical, macromolecular complexes of lipids and specific protein called Apo-protein.
  • 4. What are the functions of lipoproteins? • 1. They keep water insoluble lipids in solution of aqueous plasma. • 2. Provide mechanism for transporting their lipid components to and from the tissue.
  • 5. What is the general composition of plasma lipoproteins? They contain neutral lipid core made of TG , Cholesteryl esters and shell of amphipathic phospholipids, Unesterified cholesterol and apoprotein.
  • 6. HOW ARE THE LIPOPROTEINS CLASSIFIED? Classified on the basis of 1.COMPOSITION 2.DENSITY and 3.ELECTRO PHORETIC MOBILITY
  • 7. Name the classes of lipoproteins? • 1. Chylomicron • 2. Very low density lipoproteins (VLDL). • 3. Low density lipoproteins (LDL). • 4. High density lipoproteins (HDL). • 5. Free fatty acids – Albumin complex
  • 8. Arrangement of lipoprotein on their Size and Density Lipoprotein class Size Density Chylomicrone 1000 to 10,000A Less than 0.96 VLDL 300 to 700A Upto 1.006 LDL 150 to 250A Upto 1.063 HDL 75 to 100A Above 1.063
  • 9. Lipoprotein composition TG C & CE PL Apo protein Chylo- microne 90 % 5 % 3 % 2 % VLDL 60 % 20 % 15 % 5 % LDL 08 % 50 % 22 % 20 % HDL 05 % 25 % 30 % 40 %
  • 12. Write the functions of apolipoproteins. • 1. Provide recognition sites for cell surface receptors. • 2. Serves as coenzymes • 3. Some are required as a structural part and can not be replaced or removed.
  • 13. Write the functions of CHYLOMICRONES. • Transport mainly Exogenous Tri acyl glycerol from intestine to Liver, adipose tissue and muscle. • TAG either absorbed from food or Synthesized in enterocytes ) Adipose Muscle
  • 14. Write the functions of Very Low Density Lipoproteins ( VLDL ) • Transports mainly endogenous Tri acyl glycerol from Liver to extra hepatic tissues • Endogenous Tri acyl glycerol Synthesized in hepatocyte
  • 15. Write the functions of Low Density Lipoproteins (LDL) • Transports mainly Cholesterol and cholesteryl esters from Liver to extra hepatic tissues cholesterol
  • 16. Write the functions of High Density Lipoproteins (HDL) • Transports mainly Cholesterol and Cholesteryl esters from extra hepatic tissues to Liver • Serves to hold apo- c & apo-e for use cholesterol
  • 17. Write the functions of Free fatty acid Albumin complex • Transports mainly free fatty acids released from adipose tissue to Liver for oxidation FFA Adipose Adipose Adipose FFA FFA FFA
  • 18. Enzymes in lipoprotein metabolism • Lecithin cholesterol acyl transferase • L CAT : • Catalyses transfer of Sn2 FA of phospholipids to cholesterol. • Converts polar cholesterol to non polar cholesteryl esters • Shift of cholesterol form periphery to core
  • 19. • Lipoprotein lipase • Heparin sensitive lipase Catalyses hydrolysis of chylomicron and VLDL Located on capillary surface Responsible for generating FA and glycerol in tissue Enzymes in lipoprotein metabolism
  • 20. • Hepatic lipase Catalyses hydrolysis of TAG and Phospholipids of HDL and IDL Located in sinusoid s of liver Responsible for metabolic degradation of HDL and IDL Enzymes in lipoprotein metabolism
  • 21. • Acid lipase • Intracellular lipase Catalyses hydrolysis of TAG and cholesteryl esters in lysosomes Located in lysosome , Optimum pH acidic Responsible for degradation of lipoprotein taken up by receptor mediated endocytosis Enzymes in lipoprotein metabolism
  • 22. Lipoprotein Receptors E B10 0 E Receptor for chylomicron remnants Receptor for LDL and IDL X unknownReceptor for HDL Receptor for LDL does not recognize VLDL due to presence of C ii Apo C ac t as coenzyme for lipo protein lipase
  • 24. Type I Hyper LP Lplipase def Apo Cii def
  • 25. METABOLISM OF VLDL AND LDL Lipoprotein metabolism 2
  • 26. Type III Hyper LP Fatty liver Type II Hyper LPLDL not removed
  • 27. CELLUAR UPTAKE AND DEGRADATION OF LDL Lipoprotein metabolism 3
  • 28.
  • 32. Apo – A1 Apo – B Bad cholesterol LDL Good cholesterol HDL
  • 33. Lipoproteins and Disease • Hyperlipoproteinemias and hypolipoproteinemias are due to malfunctions in the synthesis and catabolism of lipoproteins.
  • 34. HYPERLIPOPROTEINEMIA TYPE -- I Deficiency of enzyme lipoprotein lipase VLDL and Chylomicrons are not utilized High TAG level in the blood
  • 35. HYPERLIPOPROTEINEMIA TYPE -- II Lack of removal of LDL form the blood Not recognising Apo B100 in LDL receptor High Cholesterol level in the blood High risk of CHD and Atherosclerosis
  • 36. HYPERLIPOPROTEINEMIA TYPE -- III Deficiency of enzyme mobilising VLDL and LDL from circulation Apo E deficient, impairs uptake IDL level increase in the blood
  • 37. HYPERLIPOPROTEINEMIA TYPE -- IV Due to imbalance between synthesis and clearance of VLDL in circulation
  • 38. HYPERLIPOPROTEINEMIA TYPE -- V Lipoprotein lipase deficient or utilisation of VLDL and Chylomicrons
  • 39. HYPO LIPOPROTEINEMIA A BETA LIPOPROTEINEMIA 1. Serum LDL and VLDL level decreased due to absence of Apo B 2. Lack of formation of Chylomicron after high fatty meal 3. Result malabsorption, steatorrhea and cholesterol deposition under skin as nodules
  • 40. HYPO LIPOPROTEINEMIA – II Tangier disease 1. Deficiency of Serum HDL due to absence of Apo A1 2. Result cholesterol ester deposition in skin , cornea and blood vessels. 3. Increased risk of premature CHD
  • 41. Diseases Genetic defects Risk LPL defect Reduced level of LPL Pancreatitis Apo C-11 defect Inability to synthesize Apo C-11 Pancreatitis A beta lipoproteinemia Inability to synthesize Apo B Neurological defect An alpha lipoproteinemia Inability to synthesize Apo A Cholesteryl esters storage in abnormal sites Diseases associated with lipoprotein metabolism
  • 42. Apo B48 Apo A Intestinal mucosa Liver Choesterol Fatty acid Apo A Apo C Apo E E Receptor for chylomicron remnants B48 chylomicron remnants B48E AE C II HDL Ch PL Ch TAG Ch TAG Glycerol Free FA Lipoprotein lipase C IIE Nacent chylomicron A E C II CM Ch PL B48 A 1 2 3 4

Editor's Notes

  1. Receptor mediated endocytosis