1. LIPIDS AND LIPOPROTEINS Dr. Gamal Gabr

2. Lecture Outline What are lipoproteins? What do they do?
Basic structure of lipoproteins
Hyperlipoproteinemia
Role of lipoproteins in atherosclerosis

3. What are lipoproteins and why do we need them?
Lipoproteins are a handful of different molecules that interact with water insoluble fat molecules, and transports those fats in the plasma
Different lipoproteins are responsible for the transportation of different fats
Lipoproteins allow fat to be dissolved into the plasma

4. What are lipoproteins?
Molecular complexes that consist of lipids and proteins. They function as transport vehicles for lipids in blood plasma.
Lipoproteins deliver the lipid components (cholesterol and triglyceride etc.) to various tissues for utilization.
Inner droplet of neutral (water-insoluble core lipids); primarily triglycerides and cholesteryl esters
A solubilizing surface layer of phospholipids and unesterified cholesterol
Specific proteins (apolipoproteins) attached to the outer lipid layer through their specific lipophilic domains

5. There are 4 types of lipoproteins Chylomicrons
Transport of dietary triglycerides from the GI tract to the liver
Very Low Density Lipoproteins ( VLDL )
Transport of triglycerides from the liver to tissues for storage and energy
Low Density Lipoproteins ( LDL )
Transports cholesterol to peripheral tissues
High Density Lipoproteins ( HDL )
Transports cholesterol away from the peripheral tissues to the liver

6. Triglycerides
Glycerol with 3 attached fatty acids
Exogenesis source : Dietary
Endogeneous : Liver and tissue storage
95 % of body fat is triglycerides
Energy source when plasma glucose is decreased
Triglyceride catabolism is regulated by lipase, epinephrine and cortisol
Triglycerides transported by Chylomicrons ( exogeneous ) and VLDL ( endogenous )

7. Transported by HDL and LDL
Cholesterol
Found only in animals
Important component of membranes, steroid hormones, bile and Vitamin D
Exogeneous cholesterol comes from diet
Endogeneous cholesterol is synthesized by the liver
70 % of cholesterol associated with cellular components
30 % is in the plasma ( ⅓ free form , ⅔ esterfied )
Transported by HDL and LDL

8. Phospholipids
Important components of cell membranes
Lecithin and sphingomyelin are utilized to determine fetal lung maturity from amniotic fluid ( L / S Ratio )
Glycolipids
Lipids with a carbohydrate component
ABO antigen are glycolipids

9. Structure of lipoprotein
Hydrophobic lipids (TG, CE) in the core
Amphiphilic lipids (C, PL) and proteins on the surface

10. Classification of plasma lipoproteins according to their density
Chylomicron (CM)
Very low density lipoprotein (VLDL)
Intermediate density lipoprotein (IDL)
Low density lipoprotein (LDL)
High density lipoprotein (HDL)

11. Apoliproproteins
Outer protein “shell” of the lipoprotein molecule
The protein – lipid interaction allows the water insoluble lipid to become soluble in plasma
The apolipoprotein is responsible for the interactions with cell membranes and enzymes to transport lipids to specific locations
Lipoproteins
Classified according to density and electrophoresis migration
Lipoproteins differ in their sizes, weights, chemical composition and artherogenicity ( association with heart disease )
There are four main types of lipoproteins
CHYLOMICRONS
VLDL
LDL
HDL

12. Chylomicrons
Transports exogeneous ( dietary ) triglycerides
% by weight is triglycerides
Absent from fasting plasma
Removed from the plasma within 6 hours by the liver
Inadequate clearance produces a creamy layer on the plasma
VLDL ( Very Low Density Lipoproteins )
Transports endogeneous triglycerides from liver to tissues
% by weight is triglycerides
Excess dietary carbohydrates are converted to triglycerides by the liver
LDL ( Low Density Lipoproteins )
Transports cholesterol from liver to the tissues
Synthesized in the liver
Approximately 50 % by weight cholesterol
Most atherogenic lipoprotein … “ Bad Cholesterol “

13. HDL ( High Density Lipoprotein )
Transports excess cholesterol from the tissues back to the liver ( reverse transport )
Synthesized in the liver and intestines
Composition
30% PHOSPHOLIPIDS
20% CHOLESTEROL
50% APOPROTEIN
The “good “ cholesterol

14. Characteristics of human plasma lipoproteins
CM VLDL LDL HDL
Density (g/mL) <
Diameter (nm)
Apolipoprotein A,C,E,B A,C,E,B B A,C,D,E
Composition (%)
Proteins
Lipids
Lipid composition (%) TG
CE+C PL
Free fatty acid

16. Lipoprotein physiology and metabolism
Water insoluble lipids are digested unto more water soluble ( polar ) compounds in the GI tract
Triglycerides are digested into fatty acids
Cholesterol – esters are converted into free cholesterol
Fatty acids are converted into triglycerides by the liver anf adipose tissues ( fat )
Most cholesterol synthesis occurs in the liver - Most cholesterol lowering drugs target this synthesis
Cholesterol is a main component of bile ( needed for dietary absorption of fat )

17. Exogeneous Pathway
Transport of dietary lipids, mostly the chylomicrons transportation of triglycerides to the liver
Endogeneous Pathway
Transportation of lipids from the liver to the tissues ( VLDL & LDL )

18. Effects of hormones
Insulin
Remember, insulin always decreases plasma glucose
Inactivates lipase … decreases lipolysis and the catabolism of triglycerides to fatty acids / glucose
Stimulates lipogenesis ( fatty acid conversion to triglycerides )
Insulin helps make fat
In diabetes mellitus, insulin deficiency promotes the release of fatty acids and their conversion to triglycerides by the liver

19. Apolipoproteins Act as structural components of lipoproteins
Recognize the lipoprotein receptors on cell membrane surface as ligand
Activate/inhibit enzymes involved in lipoprotein metabolism

20. Apo AI: Activator LCAT
Apo AII: Inhibitor of hepatic lipase (HL)
Apo A-IV: Activator of LCAT
Apo B-100 (liver, 4564 Aa): structure, ligand
Apo B-48 (intestine, 2152Aa): structure
Apo C-I : Activator of LCAT
Apo C-II: Activator of LPL
Apo C-III: Inhibitor of LPL
Apo D: Function unknown
Apo E: Ligand

21. What do lipoproteins do?
Serve to transport lipids and lipid-soluble compounds between tissues and organs
Substrates for energy metabolism (TG)
Essential components for cells (PL, C)
Precursors for hormones (C)
Lipid soluble vitamins
Precursors for bile acids (C)

22. Lipoprotein Top 10
Lipoproteins transport various lipids ( fats ) thru plasma to different locations
High relationship between specific lipoproteins and CAD
Apolioproteins are the protein “shells” that interact with lipids and allow them to be water soluble
HDL ( Good Cholesterol ) transports cholesterol away from tissues to the liver
LDL ( Bad Cholesterol ) transports cholesterol to the tissues from the liver
VLDL transports endogenous triglycerides from liver to tissues
Chylomicrons transport exogenous triglycerides from GI tract to liver