How do HDLs and CETP actually help the body?

[Polycherry]

I know that HDLs collect cholesterol from peripheral tissues and transport it back to the liver using SRB1 - Reverse cholesterol transport and dumping it in bile. So the tissue is producing some extra cholesterol (why would it? apart from some atherosclerotic condition) and our HDL gets it back to the liver. This is a bit fine. But then there is CETP which is giving back the cholesterol to VLDLs. So is it not confusing that our HDL took the excess cholesterol from the tissues only to give it back via VLDL?

So my questions -

Q1 - Why would a tissue have extra cholesterol?(when excellent feedback mechanisms exist - eg. SREBP SCAP INSIG path). Does the HDL pathway make sense only when there is some atherosclerosis?

Q2. Reverse Cholesterol transport refers to the SRB1 part only or SRB1 + CETP combined?

Q3. What is the rationale behind handing over the cholesterol back to VLDLs by CETPs? I know that considerable LDLs get back to the liver too but isnt just SRB1 pathway just fine? Why is it so important to equilibriate your lipid content across lipoproteins? I understand this is the mechanism how torectrapib works but presence of CETP in the body signifies that it must have some ulterior motive, right?

please help

---

Members don't see this ad.

 

[tasar1898]

For Q3 , kaplan biochem says that CETP transfers esterified cholesterol to the other lipoproteins and exchanges it with their own ''free'' cholesterol , which is also esterified by LCAT . The rationale for this is that free cholesterol can mess other cell membranes by changing their cholesterol concentration . Esterified chol stays in the lipoprotein and doesn't cause problems..

For the other questions , I doubt anyone cares that much about lipid metabolism here ... maybe you should ask in a biochem specific forum?? Good luck anyways!

Edit: I think that SRB2 facilitates exchange between HDL and tissues , SR-B1 is the one that macrophages in atheromas use , and it can't be saturated

 

[Polycherry]

For Q3 , kaplan biochem says that CETP transfers esterified cholesterol to the other lipoproteins and exchanges it with their own ''free'' cholesterol , which is also esterified by LCAT . The rationale for this is that free cholesterol can mess other cell membranes by changing their cholesterol concentration . Esterified chol stays in the lipoprotein and doesn't cause problems..

For the other questions , I doubt anyone cares that much about lipid metabolism here ... maybe you should ask in a biochem specific forum?? Good luck anyways!

Edit: I think that SRB2 facilitates exchange between HDL and tissues , SR-B1 is the one that macrophages in atheromas use , and it can't be saturated

So the exchange both ways is cholesterol?? LIppincot says this. And yeah! should be srb2 Thanks

 

[tasar1898]

In my opinion , you shouldn't get bogged down with all this biochem crap,we are not trying to get a biochem PhD , just know the basics , i.e -- VLDL starts as Lots of TG and free Cholesterol , then it loses TG's via the action of Lipoprotein Lipase in fat cells endothelium , and becomes IDL with a little TG and still lots of free cholesterol , then it crashes with HDL that esterifies its cholesterol and loses the extra apob-100 and apoE copies and becomes LDL ( Contains Cholesterol Esters and a single copy of B-100 ) . The medical importance here is that if the single copy of B-100 gets randomly oxidized , LDL can't be uptaken by LDL receptors in liver and is free to move around forever and cause atherosclerosis ..

 

[worldbeater]

This is like one of the top 5 concepts I find the most difficult on the exam, I just try to to stick to knowing the basic sequence of events and derive off that if they ask questions that are more detailed..