Reverse cholesterol transport
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Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream.
Cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
from non-hepatic peripheral tissues is transferred to HDL by the ABCA1 (
ATP-binding cassette transporter The ATP synthase, ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene family, gene families. It is represented in all extant taxon, extant Phylum ...
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Apolipoprotein A1 Apolipoprotein AI (ApoA-I) is a protein that in humans is encoded by the ''APOA1'' gene. As the major component of HDL particles, it has a specific role in lipid metabolism. Structure ''APOA1'' is located on chromosome 11, with its specific lo ...
(ApoA-1), the major protein component of HDL, acts as an acceptor, and the phospholipid component of HDL acts as a sink for the mobilised cholesterol. The cholesterol is converted to cholesteryl esters by the
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
LCAT ( lecithin-cholesterol acyltransferase). The cholesteryl esters can be transferred, with the help of CETP ( cholesterylester transfer protein) in exchange for triglycerides, to other
lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, su ...
s (such as
LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
and VLDL), and these lipoproteins can be taken up by secreting unesterified cholesterol into the bile or by converting cholesterol to bile acids.
Adiponectin Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ''ADIPOQ'' gene and it is produ ...
induces ABCA1-mediated reverse cholesterol transport from macrophages by activation of PPAR-γ and LXRα/β. Uptake of HDL2 is mediated by
hepatic lipase Hepatic lipase (HL), also called hepatic triglyceride lipase (HTGL) or LIPC (for "lipase, hepatic"), is a form of lipase, catalyzing the hydrolysis of triacylglyceride. Hepatic lipase is coded by chromosome 15 and its gene is also often referre ...
, a special form of
lipoprotein lipase Lipoprotein lipase (LPL) (EC 3.1.1.34, systematic name triacylglycerol acylhydrolase (lipoprotein-dependent)) is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water-solubl ...
found only in the liver. Hepatic lipase activity is increased by
androgen An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This in ...
s and decreased by
estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...
s, which may account for higher concentrations of HDL2 in women. Discoidal (Nascent) HDL: Initially, HDL is discoidal in shape because it lacks esterified cholesterol but as it keeps accumulating free cholesterol in it, the enzyme LCAT keeps esterifying the free cholesterol. When the HDL molecule is cholesterol rich, its shape is changed into more spherical and it becomes less dense (HDL 2). This is carried to the liver to release all the esterified cholesterol into the liver.


References

{{DEFAULTSORT:Reverse Cholesterol Transport Biochemistry Lipids Lipoproteins Metabolism