Lipoproteins, 09

2. Lipoprotein
Metabolism
By
Amr S. Moustafa, M.D.; Ph.D.

3. Lipids compounds:
Relatively water insoluble
Digestion: after Emulsifiction
Absorption: as Micelles
Blood transport: as Lipoproteins
Introduction

4. Mixed Micelles

5. Lipoprotein Structure

6. Composition
of
Lipoproteins

7. Ultracentifugation
of
Lipoproteins

8. Lipoprotein Electrophoresis

9. Secretion of Chylomicron from Intestine
Fat-Soluble vitamins
Microsomal TAG-transfer protein & assembly of CM in ER

10. Intestinal Apo B-48
Post-transcriptional editing of Apo B gene
Deamination of cytosine to uracil
Insertion of stop codon (Nonsense)
Translation of only 48% of Apo B gene

11. Chylomicron Metabolism

12. Lipoprotein Lipase
Synthesis: Adipocytes and muscle cells
Extracellular enzymes (isomer forms)
Anchored by HS to capillary walls
Most tissues, but not adult liver
Activated by: Apo C-II & Heparin
Deficiency: Type 1 hyperlipoproteinemia

13. Lipoprotein Lipase
Insulin: Synthesis & transfer
Isomer forms: Different Km
(Adipose :Large, But, Heart: Small)
Highest concentration: Cardiac muscle
Plasma clearing effect: Heparin
CONT’D

14. VLDL Metabolism

15. Lipid-Transfer Protein

16. LDL: Receptor-Mediated Endocytosis
Degraded
Recycled

17. Athersclerotic plaque Formation
(SR-A)

18. HDL Metabolism
(SR-B1)
VLDL
CETP
Hepatic Lipase
Reverse Cholesterol Transport

19. Lipoprotein (a) or
LP(a)
LP(a): ~ identical to LDL
Apo(a): Additional apoprotein
covalently-linked to apo B-100
Homologous to plasminogen
Interferes with breakdown of blood clots
& triggers heart attack
LP(a) plasma level: Risk for CHD

20. Lipoprotein (a) or
LP(a)
Factors Affecting Circulating Levels:
Genetic set-up
Sex (estrogen )
Diet (Trans FA )

21. Lipoprotein-related Diseases
(A) Hyperlipoproteinemia
Type I Hyperlipoproteinemia
Familial Lipoprotein lipase deficiency
Type IIa Hyperlipoproteinemia
Familial hypercholestrolemia
Functional defect of LDL-receptor
Type III Hyperlipoproteinemia
Familial dysbetalipoproteinemia
Apo E-2 isoform
Hypercholestrolemia & atherosclerosis

22. Lipoprotein-related Diseases
(B) Hypolipoproteinemia
Congenital abetalipoproteinemia
Defect in TAG-transfer protein
Inability to load Apo B with lipids
No CM or VLDL formation
TAG accumulation: intestine & liver
(C) Fatty Liver (hepatic steatosis)
Decreased secretion of VLDL
Obesity, DM, Chronic alcoholism

23. Steroid Hormones

24. Steroid Hormones:
Mechanism of Actions
Steroid/Thyroid Superfamily:
Steroid Hormones
Thyroid Hormones
Calcitriol (Vitamin D)
Retinoic acid (Vitamin A)