LDL Receptor

 The LDL receptor (R-LDL) is expressed on the mem brane of cells of the liver and most tissues, where it mediates endocytosis of LDL, remnant chylomicrons, and IDL through interaction with ApoB-100 and ApoE. Following internalization of the R-LDL/LDL complex, the cleavage of the receptor–lipoprotein bond occurs; the receptor is recycled and transported to the membrane, while the lipoprotein undergoes lysosomal degradation, which leads to the release of its protein and lipid components. Cholesterol inhibits the expression of the gene encoding for hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, a key enzyme in cholesterol biosynthesis, and the gene encoding for the LDL receptor. In addition, cellular cholesterol is oxidized, and oxidized sterols activate LXR, a nuclear hormone receptor that acts as a transcription factor and stimulates transcription of the ubiquitin E3 ligase gene, which mediates ubiquitination and degradation of the LDL receptor. Finally, the LDL receptor interacts with PCSK9 (proprotein convertase subtilisin/kexin type 9), a protein that promotes its early lysosomal degradation, preventing its recycling to the plasma membrane. PCSK9 gene mutations with loss of function are associated with increased LDL receptor activity and reduced LDL levels. Conversely, mutations resulting in increased PCSK9 protein activity are associated with reduced LDL receptor activity, resulting in increased LDL levels that can lead to severe familial hypercholesterolemia.

Class B Scavenger Receptor Type 1 (SR-B1)

The receptor belongs to the scavenger receptor super family and is expressed in the liver, adrenal glands, ovaries, testes, macrophages, and other cell types. In liver and steroid- producing cells, it mediates the selective uptake of cholesterol esters from HDL.

ATP-Binding Membrane Cassette Transporter A1 (ABCA1)

 The ABCA1 is expressed in most cells of the body, including hepatocytes, enterocytes, and macrophages, where it mediates the transport of cholesterol and phospholipids from cells to lipid-poor HDLs (pre-beta HDLs). Therefore, it plays a key role in the initial lipidation processes of nascent HDLs.

ATP-Binding Cassette Transporter G1 (ABCG1)

The ABCG1 is expressed in many cell types and mediates cholesterol efflux from cells to mature HDLs.

ATP-Binding Cassette Transporters G5 and G8 (ABCG5/ABCG8)

 The ABCG5/ABCG8 are expressed in the liver and intestine as heterodimers. In the intestine, these transporters mediate the flow of cholesterol from the enterocyte to the intestinal lumen, thereby reducing its absorption. In the liver, however, they promote the transport of cholesterol into the bile.

Acylcoa-Cholesterol Acyltransferase (ACAT)

The ACAT is an enzyme that mediates the esterification of cholesterol with a fatty acid molecule. Esterification makes cholesterol even more lipophilic and suitable for storage or transport via plasma lipoproteins.

Lipoprotein Lipase (LPL)

 LPL is an enzyme synthesized in numerous tissues, including muscle and adipose tissue, secreted and anchored to heparan sulfate on the luminal surface of endothelial cells.

LPL catalyzes the hydrolysis of triglycerides, chylomicrons, and VLDL, releasing glycerol and fatty acids, which, once released, are picked up by cells. Triglyceride catabolism leads to the conversion of chylomicrons into chylomicron remnants and VLDL into IDL. LPL requires ApoC-II as a cofactor. In addition, ApoA-V also plays a key role in the activation of the enzyme. In contrast, ApoC-III and ApoA-II inhibit its activity. Insulin stimulates the expression of LPL, whereas the activity of the enzyme is reduced in patients with poorly controlled diabetes, and this could impair the metabolism of triglyceride-rich lipoproteins, leading to hypertriglyceridemia.

Hepatic Lipase

Hepatic lipase is located on the sinusoidal surface of hepatocytes, where it mediates the hydrolysis of triglycerides and phospholipids of IDL and LDL, leading to the formation of smaller particles (IDLs are converted into LDLs, and large LDLs are converted into smaller particles).

Lecithin Cholesterol Acyltransferase (LCAT)

LCAT is an enzyme synthesized in the liver and secreted into plasma, where it circulates mostly associated with HDLs. On HDLs, it catalyzes the synthesis of cholesterol esters, facilitating the transfer of fatty acid from the 2-position of lecithin to the hydroxyl group in 3-position of cholesterol. ApoA-I serves as a cofactor for LCAT.

The free cholesterol on the surface of HDL, once esterified, is transferred within the particle. In this way, HDL pro motes the uptake of free cholesterol through the reduction of cholesterol on the surface of HDL.

Cholesteryl Ester Transfer Protein (CETP)

It is a glycoprotein synthesized in the liver and released into plasma, where it mediates the transfer of cholesteryl esters from HDL to VLDL, chylomicrons, and LDL, and the trans fer of triglycerides from VLDL and chylomicrons to HDL. Inhibition of CETP activity leads to an increase in HDL cholesterol and a decrease in LDL cholesterol.

مواضيع ذات صلة

homocysteine (Hcy)

HIV serologic and virologic testing

HIV RNA quantification (HIV viral load)

Lipoproteins

Retinol Binding Protein

Direct Visualization Of The Organism

Direct Detection Methods for Bacillus and Similar Organisms

HIV drug resistance testing (HIV genotype)

herpes simplex (Herpesvirus types 1 and 2, Herpes simplex virus types 1 and 2 [HSV 1, HSV 2], Herpes genitalis)

hepatitis virus studies

Biomarkers of Nutritional Status

Malnutrition