Reverse cholesterol transport
Encyclopedia
Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver via the plasma.

Cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 from non-hepatic peripheral tissues is transferred to HDL by the ABCA1
ABCA1
ATP-binding cassette transporter ABCA1 , also known as the cholesterol efflux regulatory protein is a protein which in humans is encoded by the ABCA1 gene...

 (ATP-binding cassette transporter). ApoA-1 acts as an acceptor, and the phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

 component of HDL acts as a sink for the mobilised cholesterol.
The cholesterol is converted to cholesteryl ester
Cholesteryl ester
A cholesteryl ester is, as its name would imply, an ester of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl group of cholesterol. Cholesteryl Esters have a lower solubility in water than Cholesterol and, in other words, are more hydrophobic...

s by the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 LCAT (lecithin-cholesterol acyltransferase
Lecithin-cholesterol acyltransferase
Lecithin-cholesterol acyltransferase is an enzyme that converts free cholesterol into cholesteryl ester , which is then sequestered into the core of a lipoprotein particle, eventually making the newly synthesized HDL spherical and forcing the reaction to become...

).
The cholesteryl esters can be transferred to other lipoprotein
Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids water-bound to the proteins. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins...

s (such as LDL), and these lipoproteins can be taken up by the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 through its LDL receptor
LDL receptor
The Low-Density Lipoprotein Receptor is a mosaic protein of ~840 amino acids that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100 which is embedded in the phospholipid outer layer of LDL particles...

s.

However, the receptor SR-B1 (scavenger receptor class B1
SCARB1
Scavenger receptor class B member 1 also known as SR-BI is a protein that in humans is encoded by the SCARB1 gene. SR-BI functions as a receptor for high-density lipoprotein....

) present on the liver cells’ plasma membranes mediates most of the liver’s uptake of cholesteryl esters from HDL in the absence of uptake of apolipoprotein
Apolipoprotein
Apolipoproteins are proteins that bind lipids to form lipoproteins and transport the lipids through the lymphatic and circulatory systems....

s. The overall process by which HDL removes cholesterol from extrahepatic tissues and returns it to the liver is called reverse cholesterol transport. Once in the liver, the cholesteryl esters are converted to cholesterol and enter the general pool.
Therefore, the liver can eliminate cholesterol from the body by secreting unesterified cholesterol into the bile
Bile
Bile or gall is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver of most vertebrates, that aids the process of digestion of lipids in the small intestine. In many species, bile is stored in the gallbladder and upon eating is discharged into the duodenum...

 or by converting cholesterol to bile acid
Bile acid
Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...

s.

Uptake of HDL2 is mediated by hepatic lipase
Hepatic lipase
Hepatic lipase is a form of lipase. It is expressed in the liver and adrenal glands.One of the principal functions of hepatic lipase is to convert IDL to LDL.-Clinical significance:...

, a special form of lipoprotein lipase
Lipoprotein lipase
Lipoprotein lipase is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins , into two free...

 found only in the liver. Hepatic lipase activity is increased by androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...

s and decreased by estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

s, which may account for higher concentrations of HDL2 in women.
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