CETP vs LCAT

[alicealicealice]

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Can anyone give a simple explanation of the role of these two and clinical relevance (if any)?
Although I have all the lipoproteins etc memorized (bascially everything in FA), I have a hard time understanding the big picture of cholesterol metabolism, especially reverse choleterol transport.

Thanks in advance for any enlightenment

 

[Praxia]

Cholesterol is a polar molecule and a major part of cell membranes. Since it's polar, it lies on the surface of lipoproteins(LDL). So when these LDL particles bump into cells, they transfer their cholesterol to the cell's membrane.
If there's too much of cholesterol in the membranes, receptors and other pumps etc. don't function efficiently.
To solve this problem, it should be converted to cholesterol ester (which is non-polar) using LCAT. HDL's apolipo A activates LCAT.
Now, HDL takes chol from IDL and LDL and converts it to chol esters and gives it back(using CTEP) to LDL and IDL. and since chol ester is NON-POLAR, it lies in the core of these lipoproteins, unable to jump onto the membranes of any more cells.

 

[Praxia]

About the clinical aspect.
HDL gets rid of it's Chol esters by two ways:--
1. DIRECT-via SRB1 receptors on liver.
2. INDIRECT-via CETP tranferring chol esters to IDL and LDL.

The development of CETP inhibitors is underway. These will be used in hypercholestrolemia, since the INDIRECT pathway has the ability to saturate LDLs with excessive cholesterol esters (and therefore, initiate atherosclerosis). With CETP inhibitors, DIRECT pathway will carry out the business of chol ester tranfer.

 

[ulikedaggers]

Correct me if I'm wrong, but CETP exchanges cholE with TGs, not cholE with chol. Reverse cholesterol transport is removal of cholesterol from extrahepatic membranes by HDL via ABCA1, then esterification of chol by LCAT, then transfer of cholE from HDL to LDL in exchange for TG via CETP.

Then the hepatocyte can takeup the HDL and hepatic lipase can breakdown the TGs.