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Department of Biochemistry, Nepalgunj Medical College, Nepal
Formation and secretion
Sunday, July 10,
2016
Rajesh Chaudhary
1
Biomedical importance
Lipoprotein mobilization and utilization after oxidation
during the energy requirement process or stage.
Abnormalities in lipoprotein metabolism leads to either
hypo- or hyperlipoproteinemia.
Example: Hypertriacylglycerolemia during T2DM.
Hypercholesterolemia and premature atherosclerosis.
Sunday, July 10,
2016
Rajesh Chaudhary
2
Plasma consists of: triacylglycerol
(16%), phospholipids (30%),
cholesterol (14%), cholesterol ester
(36%), and free fatty acids (4%).
Sunday, July 10,
2016
Rajesh Chaudhary
3
4 major lipid classes
1. Chylomicrons
2. VLDL
3. LDL
4. HDL
Sunday, July 10,
2016
Rajesh Chaudhary
4
4 major plasma lipoproteins
Lipoprotein particle
Sunday, July 10,
2016
Rajesh Chaudhary
5
Lipoprotein particle
Sunday, July 10,
2016
Rajesh Chaudhary
6
Density of lipoproteins
Sunday, July 10,
2016
Rajesh Chaudhary
7
𝐋𝐢𝐩𝐢𝐝
𝐏𝐫𝐨𝐭𝐞𝐢𝐧
If,
Is high, density is
lower and vice-
versa.
Plasma lipoproteins
Spherical macromolecular complexes of
lipids + specific proteins
(apolipoproteins / apoproteins)
Examples: Chylomicrons, VLDL, LDL,
HDL.
Lipid deposition contributes to plaque
formation, causing the narrowing of
blood vessels (atherosclerosis).
Sunday, July 10,
2016
Rajesh Chaudhary
8
The distribution of apolipoproteins
characterizes the lipoproteins
Of HDL: Apolipoprotein A
Of VLDL and LDL: apolipoprotein B (B-100)
Of Chylomicrons: apolipoprotein B (B-48) – truncated form of
apolipoprotein B.
Apo C I, C II, C III and apoE are freely transferrable between
lipoproteins.
NOTE: B-100 is synthesized in liver while B-48 in intestine.
Sunday, July 10,
2016
Rajesh Chaudhary
9
So, what are the functions of
apolipoproteins?
1. They can form part of the structure of
lipoproteins.
2. They are enzyme cofactors. (C-II for lipoprotein lipase)
3. They acts as ligands to interact with the receptors
in tissues.
Sunday, July 10,
2016
Rajesh Chaudhary
10
Formation and secretion of
Chylomicrons and VLDL
Sunday, July 10,
2016
Rajesh Chaudhary
11
ApoB
ApoB +
lipoprot
ein
ApoB +
lipoprote
in
+carboh
ydrates
Formation and secretion mechanism
of both Chylomicrons and VLDL are
common. Why?
Sunday, July 10,
2016
Rajesh Chaudhary
12
NOTE: The inability of particulate lipid of the size
of chylomicrons and VLDL to pass through
endothelial cells of capillaries without prior
hydrolysis is probably the reason dietary fat enters
the circulation through lymphatic and not through
the hepatic portal system.
Sunday, July 10,
2016
Rajesh Chaudhary
13
-- Harper’s Illustrated Biochemistry
Abetalipoproteinemia and apoB
ApoB is not able to function because of a defect in a
triacylglycerol transfer protein which prevents loading of the
apoB with lipid; therefore, lipoprotein containing this
apolipoprotein are not formed, and lipid droplets accumulate
in the intestine and liver.
Sunday, July 10,
2016
Rajesh Chaudhary
14
Characteristics of abetalipoproteinemia
 Vitamin deficiency because of inability of the cells to
absorb vitamins – particularly fat-soluble vitamins – Vit. E
in particular.
Failure to gain weight, growth retardation, diarrhea,
abnormal star-shaped RBC, fatty, foul-smelling stools.
Impaired nervous system, poor muscle coordination, ataxia,
progressive degeneration of retina.
Sunday, July 10,
2016
Rajesh Chaudhary
15
Catabolism of chylomicrons and VLDL
Chylomicrons and VLDL are very rapidly metabolized.
Triacylglycerol of chylomicrons and VLDL are hydrolyzed
by lipoprotein lipase.
The action of lipoprotein lipase forms remnant lipoproteins.
The liver is responsible for the uptake of remnant
lipoproteins.
Sunday, July 10,
2016
Rajesh Chaudhary
16
Sunday, July 10,
2016
Rajesh Chaudhary
17
Metabolism of
Lipoprotein lipase
1. Located on the wall of blood capillaries, anchored to the
endothelium by negatively charged proteoglycan chain of
heparin sulfate.
2. Found in: Heart, adipose tissue, renal medulla, lungs,
aorta, diaphragm, lactating mammary gland and
neonatal liver.
3. Not active in adult liver.
Sunday, July 10,
2016
Rajesh Chaudhary
18
Sunday, July 10,
2016
Rajesh Chaudhary
19
Rajesh Chaudhary
20
Metabolic fate of
chylomicrons
Sunday, July 10,
2016
Rajesh Chaudhary
21
Metabolism of
Sunday, July 10,
2016
Rajesh Chaudhary
22
Sunday, July 10,
2016
23
Metabolic fate
of VLDL and
formation of
LDL
Receptors are defective in familial hypercholesterolemia.
Sunday, July 10,
2016
Rajesh Chaudhary
24
Metabolism of
Sunday, July 10,
2016
Sunday, July 10,
2016
Rajesh Chaudhary
26
Metabolism
of HDL
Sunday, July 10,
2016
Rajesh Chaudhary
27

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Lipoprotein metabolism

  • 1. Department of Biochemistry, Nepalgunj Medical College, Nepal Formation and secretion Sunday, July 10, 2016 Rajesh Chaudhary 1
  • 2. Biomedical importance Lipoprotein mobilization and utilization after oxidation during the energy requirement process or stage. Abnormalities in lipoprotein metabolism leads to either hypo- or hyperlipoproteinemia. Example: Hypertriacylglycerolemia during T2DM. Hypercholesterolemia and premature atherosclerosis. Sunday, July 10, 2016 Rajesh Chaudhary 2
  • 3. Plasma consists of: triacylglycerol (16%), phospholipids (30%), cholesterol (14%), cholesterol ester (36%), and free fatty acids (4%). Sunday, July 10, 2016 Rajesh Chaudhary 3 4 major lipid classes
  • 4. 1. Chylomicrons 2. VLDL 3. LDL 4. HDL Sunday, July 10, 2016 Rajesh Chaudhary 4 4 major plasma lipoproteins
  • 5. Lipoprotein particle Sunday, July 10, 2016 Rajesh Chaudhary 5
  • 6. Lipoprotein particle Sunday, July 10, 2016 Rajesh Chaudhary 6
  • 7. Density of lipoproteins Sunday, July 10, 2016 Rajesh Chaudhary 7 𝐋𝐢𝐩𝐢𝐝 𝐏𝐫𝐨𝐭𝐞𝐢𝐧 If, Is high, density is lower and vice- versa.
  • 8. Plasma lipoproteins Spherical macromolecular complexes of lipids + specific proteins (apolipoproteins / apoproteins) Examples: Chylomicrons, VLDL, LDL, HDL. Lipid deposition contributes to plaque formation, causing the narrowing of blood vessels (atherosclerosis). Sunday, July 10, 2016 Rajesh Chaudhary 8
  • 9. The distribution of apolipoproteins characterizes the lipoproteins Of HDL: Apolipoprotein A Of VLDL and LDL: apolipoprotein B (B-100) Of Chylomicrons: apolipoprotein B (B-48) – truncated form of apolipoprotein B. Apo C I, C II, C III and apoE are freely transferrable between lipoproteins. NOTE: B-100 is synthesized in liver while B-48 in intestine. Sunday, July 10, 2016 Rajesh Chaudhary 9
  • 10. So, what are the functions of apolipoproteins? 1. They can form part of the structure of lipoproteins. 2. They are enzyme cofactors. (C-II for lipoprotein lipase) 3. They acts as ligands to interact with the receptors in tissues. Sunday, July 10, 2016 Rajesh Chaudhary 10
  • 11. Formation and secretion of Chylomicrons and VLDL Sunday, July 10, 2016 Rajesh Chaudhary 11 ApoB ApoB + lipoprot ein ApoB + lipoprote in +carboh ydrates
  • 12. Formation and secretion mechanism of both Chylomicrons and VLDL are common. Why? Sunday, July 10, 2016 Rajesh Chaudhary 12
  • 13. NOTE: The inability of particulate lipid of the size of chylomicrons and VLDL to pass through endothelial cells of capillaries without prior hydrolysis is probably the reason dietary fat enters the circulation through lymphatic and not through the hepatic portal system. Sunday, July 10, 2016 Rajesh Chaudhary 13 -- Harper’s Illustrated Biochemistry
  • 14. Abetalipoproteinemia and apoB ApoB is not able to function because of a defect in a triacylglycerol transfer protein which prevents loading of the apoB with lipid; therefore, lipoprotein containing this apolipoprotein are not formed, and lipid droplets accumulate in the intestine and liver. Sunday, July 10, 2016 Rajesh Chaudhary 14
  • 15. Characteristics of abetalipoproteinemia  Vitamin deficiency because of inability of the cells to absorb vitamins – particularly fat-soluble vitamins – Vit. E in particular. Failure to gain weight, growth retardation, diarrhea, abnormal star-shaped RBC, fatty, foul-smelling stools. Impaired nervous system, poor muscle coordination, ataxia, progressive degeneration of retina. Sunday, July 10, 2016 Rajesh Chaudhary 15
  • 16. Catabolism of chylomicrons and VLDL Chylomicrons and VLDL are very rapidly metabolized. Triacylglycerol of chylomicrons and VLDL are hydrolyzed by lipoprotein lipase. The action of lipoprotein lipase forms remnant lipoproteins. The liver is responsible for the uptake of remnant lipoproteins. Sunday, July 10, 2016 Rajesh Chaudhary 16
  • 17. Sunday, July 10, 2016 Rajesh Chaudhary 17 Metabolism of
  • 18. Lipoprotein lipase 1. Located on the wall of blood capillaries, anchored to the endothelium by negatively charged proteoglycan chain of heparin sulfate. 2. Found in: Heart, adipose tissue, renal medulla, lungs, aorta, diaphragm, lactating mammary gland and neonatal liver. 3. Not active in adult liver. Sunday, July 10, 2016 Rajesh Chaudhary 18
  • 21. Sunday, July 10, 2016 Rajesh Chaudhary 21 Metabolism of
  • 23. Sunday, July 10, 2016 23 Metabolic fate of VLDL and formation of LDL Receptors are defective in familial hypercholesterolemia.
  • 24. Sunday, July 10, 2016 Rajesh Chaudhary 24 Metabolism of
  • 26. Sunday, July 10, 2016 Rajesh Chaudhary 26 Metabolism of HDL