1. Lipoprotein Structure, Function, and Metabolism
Lipid Transport
Lipoprotein Structure, Function, and Metabolism

2. Objectives Function of lipids. Lipoprotein structures.
Types of Lipoproteins: Function & structure.

3. Introduction
Fats are triacylglycerol containing saturated fatty acids - solid at room temp - usually from animal source (however, coconut & palm oil are saturated).
Oils are triacylglycerol containing mono- or polyunsaturated fatty acids - liquid at room temp
- usually from plant sources (however, fish oils are polyunsaturated).
Phospholipids are triacylglycerol that have had a FA containing phosphate group.
The major dietary sterol is cholesterol.

4. Health issues
Excessive dietary fat intake is associated with obesity, diabetes, cancer, hypertension and atherosclerosis.
Not more than 35% of energy intake should come from fat. Saturated fat should not make up more than 15% of the total fat intake.
Omega-3 fatty acids (20 carbons) from fish may protect against atherosclerosis. American Heart association recommends 2-3 fish meals per week. Fish oil supplements should be avoided because they may be contain concentrated toxins accumulated by the fish.  

5. FUNCTIONS OF LIPIDS: Major components of cell membranes.
Biosynthesis of fat soluble vitamins (A,E,D,K).
Biosynthetic precursors (e.g. steroid hormones from cholesterol)
Protection (e.g. kidneys are shielded with fat in fed state)
Insulation

6. LIPID DIGESTION
Lingual lipase and gastric lipase attack triacylglycerol and hydrolyse a limited number of FA.
Small Intestine - acid chyme (stomach contents) stimulates mucosa cells to release hormone (choleocystokinin) which stimulates gall bladder and pancreas to release bile and digestive enzymes respectively (bile acids help emulsify fat droplets thus increasing surface area of absorption).
Other mucosa cells release secretin which causes pancreas to release bicarbonate rich fluid to neutralize chyme.

7. Enzymic digestion of lipids in small intestine
2-monoacylglycerol

8. 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)
Non polar lipids in core (TAG and cholesterol esters)
Cholesterol

9. The four classes of lipoprotein (all contain characteristic amounts TAG, cholesterol, cholesterol esters, phospholipids and apoproteins)
Class
Diameter (nm)
Source and function
Major apoliproteins
Chylomicrons (CM)
500
Intestine. Transport of dietary TAG
A, B48, C(I,II,III) E
Very low density lipoproteins (VLDL) 43
Liver. Transport of endogenously synthesised TAG
B100, C(I,II,III) , E
Low density lipoproteins
(LDL) 22
Delivers cholesterol to peripheral tissues
B100
High density lipoproteins
(HDL) 8
Liver. Removes “used” cholesterol from tissues and takes it to liver.
A, C(I,II,III), D, E
Increasing density

10. Apolipoproteins Provide structural stability to LP
Serve as ligands for interaction with LP receptors that help determine disposition of individual particles
Act as cofactors for enzymes involved in plasma lipid and LP metabolism

11. There are many types of apolipoproteins
Apoprotein
Lipoproteins
Function(s)
Apo B-100
VLDL, IDL, LDL
Secretion of VLDL from liver
Structural protein of VLDL, IDL, and HDL
Ligand for LDL receptor (LDLR)
Apo B-48
Chylomicrons, remnants
Secretion of chylomicrons from intestine
Apo E
Chylomicrons, VLDL, IDL, HDL
Ligand for binding of IDL & remnants to LDLR
Apo A-I
HDL, chylomicrons
Major structural protein of HDL
Activator of LCAT
Apo A-II
Unknown
Apo C-I
Activation of LCAT
Apo C-II
Activator of LPL
Apo C-III
Inhibitor of LPL activity

12. Plasma Lipoproteins Structure
LP core
Triglycerides
Cholesterol esters
LP surface
Phospholipids
Proteins
cholesterol

13. Composition and properties of human lipoproteins
Lipoprotein class
Density (g/mL)
Diameter (nm)
Protein % of dry wt
Phospholipid %
Triacylglycerol % of dry wt
HDL
5 – 15 33 29 8
LDL
1.019 – 1.063
18 – 28 25 21 4
IDL 18 22 31
VLDL
0.95 – 1.006 10 50
chylomicrons
< 0.95
1 - 2 7 84
Composition and properties of human lipoproteins
most proteins have densities of about 1.3 – 1.4 g/mL and lipid aggregates usually
have densities of about 0.8 g/mL

14. Plasma Lipoproteins Classes & Functions
Chylomicrons
Synthesized in small intestine
Transport dietary lipids
98% lipid, large sized, lowest density
Apo B-48
Receptor binding
Apo C-II
Lipoprotein lipase activator
Apo E
Remnant receptor binding

15. Plasma Lipoproteins Classes & Functions
Very Low Density Lipoprotein (VLDL)
Synthesized in liver
Transport endogenous triglycerides
90% lipid, 10% protein
Apo B-100
Receptor binding
Apo C-II
LPL activator
Apo E
Remnant receptor binding

16. Plasma Lipoproteins Classes & Functions
Intermediate Density Lipoprotein (IDL)
Synthesized from VLDL during VLDL degradation
Triglyceride transport and precurser to LDL
Apo B-100
Receptor binding
Apo C-II
LPL activator
Apo E

17. Plasma Lipoproteins Classes & Functions
Low Density Lipoprotein (LDL)
Synthesized from IDL
Cholesterol transport
78% lipid, 58% cholesterol & CE
Apo B-100
Receptor binding

18. LDL molecule

19. VLDL Metabolism Nascent VLDL (B-100) + HDL (apo C & E) = VLDL
LPL hydrolyzes TG forming IDL
IDL loses apo C-II (reduces affinity for LPL)
75% of IDL removed by liver
Apo E and Apo B mediated receptors
25% of IDL converted to LDL by hepatic lipase
Loses apo E to HDL

20. Plasma Lipoproteins Classes & Functions
High Density Lipoprotein (HDL)
Synthesized in liver and intestine
Reservoir of apoproteins
Reverse cholesterol transport
52% protein, 48% lipid, 35% C & CE
Apo A
Activates lecithin-cholesterol acyltransferase (LCAT)
Apo C
Activates LPL
Apo E
Remnant receptor binding

21. Functions of HDL
converts cholesterol to cholesterol esters via the LCAT reaction
transfers cholesterol esters to other lipoproteins, which transport them to the liver (referred to as “reverse cholesterol transport)