Metabolism of High Density Lipoproteins (HDL)


 

HDL are synthesized in the liver and the small intestine. They are the lipoproteins with the higher protein content (it can reach around 50 % of the particle total weight). When secreted, they contain little cholesterol and no cholesteryl esters.

 

HDL are formed by different apolipoproteins, including Apo A1, ApoE and Apo C-II. In fact, they act as transporters of ApoE and Apo C-II from their synthesizing organ (the liver) to the plasma, making available these apoproteins to other lipoproteins.

 

Apo A-1 is the main protein in HDL, and activates LCAT, an enzyme associated to HDL.  Phospholipids are the main lipidic content of HDL (35 % of the total weight), and the enzyme Lecithin Cholesterol Acyl Transferase (LCAT) catalyze the transfer of acyl groups (fatty acids esterifies to lecithin) from lecithin to cholesterol scavenged from cell membranes of extrahepatic tissues, and from IDL and Chylomicrons remnants, producing cholesterol esters, that are dissolved in the HDL core, so these lipoproteins become the cholesterol rich HDL2 and HDL3.

 

                                      LCAT

Lecithin + Cholesterol ———->Lysolecithin + Cholesterol ester

 

Since hepatocytes have receptors for Apo A1 –the main protein of HDL- these rich-in- cholesterol lipoproteins are taken up by the hepatocytes. Consequently, the net effect is the transportation of cholesterol from the peripheral tissues to the liver (Reverse Cholesterol transport).

 

The liver excrets excess cholesterol as bile acids. That is why Cholesterol associated to HDL (HDLc) is called “good cholesterol, since it has been scavenged from the tissues and is being taken to the liver for excretion. It explains that one of the pillars in the treatment of hypercholesterolemia is to raise HDL.

 

 

In summary, the functions of HDL include:

 

a)     A reservoir of apoproteins that can be transferred to other lipoproteins.

b)    Acceptor of unesterified cholesterol (since they are rich in phospholipids, HDL can accept and solubilize cholesterol

c)     Esterification of cholesterol, (through the action of LCAT)

d)    Reverse Cholesterol Transport 

 

 

Familial LCAT deficiency is an autosomal recessive disorder characterized, biochemically, by high concentrations of free cholesterol in plasma, low concentrations of cholesterol esters and lysolecithins, and negligible plasma LCAT activity. Clinically corneal opacity (the heterocygote disease is called Fish Eye disease), sign of renal insuficiency, ateroesclerolesis, and in some cases xantelasma and hepatoesplenomegaly. These clinical manifestations are apparently the result of deposit of high quantities of unesterified cholesterol in the tissues.

 

Various pathological conditions related to low HDL cholesterol levels can be found here

 http://www.emedicine.com/med/topic3368.htm

 

 

For additional information, please follow these links:

 

HDL Definitions and Synonyms

http://ghr.nlm.nih.gov/glossary=highdensitylipoproteins

 

High Density Lipoproteins

http://en.wikipedia.org/wiki/High_density_lipoprotein

 

Physiology and Pathophysiology of HDL metabolism

http://www.lipidsonline.org/slides/slide01.cfm?tk=10&pg=2

 

LCAT deficiency: Norum Disease and Fish Eye Disease

http://www.emedicine.com/med/topic1270.htm

 

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=245900

 

Low HDL Cholesterol (Hypoalphalipoproteinemia)

http://www.emedicine.com/med/topic3368.htm

 

 

 

 

 

 

 

 

One thought on “Metabolism of High Density Lipoproteins (HDL)

  1. Pingback: Lipoproteins, cholesterol and atherosclerosis « The Biochemistry Questions Site

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