reverse cholesterol transport

Definition

Target type: biologicalprocess

The directed movement of peripheral cell cholesterol, cholest-5-en-3-beta-ol, towards the liver for catabolism. [GOC:ecd, PMID:7751809]

Reverse cholesterol transport (RCT) is a complex process that removes excess cholesterol from peripheral tissues and delivers it to the liver for excretion. This process is crucial for maintaining cholesterol homeostasis and preventing atherosclerosis. Here's a detailed breakdown:

1. **Cellular Cholesterol Efflux:** Cholesterol is first mobilized from peripheral cells, primarily macrophages in the arterial wall, by specialized proteins called ABCA1 and ABCG1. These transporters move cholesterol from the cell's interior to the extracellular space, where it interacts with high-density lipoproteins (HDL).

2. **HDL Formation and Cholesterol Loading:** HDL particles, primarily composed of phospholipids, apolipoproteins, and cholesterol esters, are assembled in the liver and small intestine. These nascent HDL particles, known as pre-beta HDL, acquire cholesterol from the peripheral cells, increasing their size and density.

3. **HDL Maturation and Cholesterol Esterification:** Once loaded with cholesterol, HDL particles undergo a series of enzymatic modifications, including the esterification of free cholesterol to cholesterol esters by the enzyme lecithin:cholesterol acyltransferase (LCAT). This process converts free cholesterol into a less soluble form, allowing for more efficient storage and transport.

4. **Cholesterol Transfer and Delivery to the Liver:** Mature HDL particles, known as alpha HDL, transport cholesterol esters to other lipoprotein particles, such as VLDL and LDL, in a process known as cholesterol transfer. This process is facilitated by cholesterol ester transfer protein (CETP). Ultimately, HDL delivers the cholesterol to the liver via two primary mechanisms:

- **Direct uptake:** HDL particles can directly interact with the liver through the scavenger receptor B type I (SR-BI), transferring cholesterol esters to the hepatocytes.

- **Reverse transport via the liver:** The liver expresses receptors that bind to HDL, leading to its internalization and subsequent cholesterol ester hydrolysis and excretion.

5. **Cholesterol Excretion:** The liver can eliminate cholesterol through several pathways, including:

- **Bile acid synthesis:** Cholesterol is converted into bile acids, which are essential for lipid digestion and excretion in the feces.

- **Direct excretion:** A small amount of cholesterol can be directly excreted in the feces.

6. **Regulation of RCT:** The efficiency of RCT is influenced by various factors, including:

- **HDL levels:** Higher HDL levels are associated with enhanced RCT.

- **Enzyme activity:** The activity of enzymes like LCAT and CETP significantly impacts cholesterol esterification and transfer, respectively.

- **Lipoprotein receptors:** The expression and function of receptors like SR-BI and hepatic HDL receptors are critical for cholesterol uptake and delivery.

7. **Clinical Significance:** Defects in RCT can lead to the accumulation of cholesterol in peripheral tissues, particularly in the arterial wall, contributing to the development of atherosclerosis and coronary heart disease. Maintaining healthy HDL levels and promoting RCT are key strategies for preventing cardiovascular disease.'
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Proteins (6)

Compounds (106)