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C1-72 Lipoproteins II
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Additional Biochemistry Flashcards





Reverse Cholesterol Transport


-Reverse Cholesterol Transport is simply

the transport of cholesterol from the

periphery back to the liver.

-Mediated by High Density Lipoprotein (HDL)

Reverse Cholesterol Transport Requires

- HDL Synthesis

-Acquisition of lipids by HDL

-Delivery of Cholesterol to the Liver


HDL Synthesis


-HDL synthesis in liver and small intestine


-produces discoidal HDL


-Discoidal HDL is phospholipid rich but cholesterol and triglyceride poor.


-Apolipoprotein A-I is the structural apoprotein of HDL.





Reverse Cholesterol Transport
Acquisition of Lipids by HDL


Nascent HDL is lipid-poor and are the smallest HDL particles
lipid poor HDLs contain apo A-I and 10-40% lipid

large spherical HDLs are produced on esterification of the free cholesterol on the HDL surface

as HDL grows, it acquires apoA-II, apoC-I, apoC-II, apoC-II, and apoE from other lipoproteins


Acquisition of Lipids by HDL.......


-through Phosphatidylcholine:cholesterol acyl transferase (PCAT) aka LCAT


-serum enzyme associated with HDL that esterfies cholesterol (adds FA).


Reverse Cholesterol Transport
 Delivery of Cholesterol to the Liver


Two Mechanisms for HDL Transport of Cholesterol to Liver

1.Via the endogenous or exogenous lipid transport pathway

  ie., through Chylomicrons or VLDLs.

2.Directly to Liver via SR-BI receptors.

  (Scavenger Receptor class B1).


Reverse cholesterol transport: 
SR-BI Receptors


-HDL delivers cholesterol to liver and steroidgenic tissues directly.


-HDL binds scavenger receptor type BI.


-HDL transfer is not dependent upon internalization and degradation.


Summary:  reverse cholesterol transport


HDL acquires free cholesterol from peripheral cells
Phosphatidylcholine:cholesterol acyltransferase (PCAT aka LCAT) esterifies free cholesterol (FC) by removing fatty acids from phospholipids (PL) and transferring them to cholesterol to produce cholesterol esters
Because they are more hydrophobic than cholesterol, cholesterol esters move into the core of the HDLs
PCAT is activated by apoprotein A-I in HDL

Cholesterol ester transfer protein (CETP) transfers cholesterol esters from HDLs to chylomicrons, VLDLs, and IDLs, LDLs

Chylomicrons remnants, IDLs, and LDLs are internalized by the liver via receptor-mediated endocytosis (a minor fraction of HDLs are directly internalized by the liver)

HDL thru SR-BI can deliver the cholesterol ester directly to liver or steroidogenic tissues w/o degradation of the lipoprotein.


Summary of HDLs


HDLs serve as acceptors for excess cholesterol, phospholipid, and apolipoproteins removed from the surface of VLDLs, IDLs, and chylomicrons during catabolism of these lipoproteins

HDLs are reservoirs for apoC-I, apoC-II, apoC-III, and apoE for use in VLDL and chylomicron assembly

HDLs deliver excess cholesterol from extra hepatic tissues to the liver and to the steroid hormone producing glands
HDL apoproteins are not degraded during this process (in contrast to the receptor mediated endocytosis mechanism)




    Atherosclerosis:  The formation of plaques in the walls of major arteries.  This constricts the lumen of the blood vessel (which impedes the flow of blood) and decreases the vessel elasticity.

    Plaque:  Regions in the intima of major arteries in which  smooth muscle cells, connective tissue, lipids, and debris accumulate.


Steps in plaque formation


1.  Injury to epithelial cell wall (may be due to mechanical damage or  cytotoxic agents such as oxidized LDLs).

2.  Monocytes are attracted to the injured area, monocytes turn into macrophages, and macrophages engulf material in the damaged area (including oxidized LDLs).

3.  Macrophages engulf oxidized LDLs and fill up with lipid, forming “foam” cells.

4.  Foam Cells accumulate, in the intima of the of the endothelial cells of the blood vessel, forming a “fatty streak”.

5.  Damaged endothelial cells release thromboxane A2, which further stimulates platelet aggregation.

6.  Damaged endothelial cells release platelet-derived growth factor (PDGF), which causes proliferation of smooth muscle cells.

7.  Cells surrounding the lesion secrete collagen, elastin, and glycosaminoglycans (GAGs), forming a fibrous cap over the damaged endothelial cells.

8.  Cells trapped in the plaque begin to die. Calcification of the plaque occurs.

9.  Rupture and hemorrhage of the encapsulated plaque can cause thrombus, occluding the blood vessel, resulting in myocardial infarction.


*Hyperlipidemias and Exam


-Hypertriglyceridemia (elevated chylomicrons) associated with lipoprotein deficiency or ApoC-II deficiency.


-Hypercholesterolemia (elevated LDL) associated with LDL receptor defects or defects of ApoB-100.


-Hypercholesterolemia (elevated LDL and chylomicron remnants) associated with deficiency of ApoE.

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