Lipoprotein
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[[Image:Chylomicron.svg|thumb|250px|'''Lipoprotein structure (chylomicron)'''<br/>
'''ApoA, ApoB, ApoC, ApoE''' ([[apolipoprotein]]s); '''T''' ([[triacylglycerol]]); '''C''' ([[cholesterol]]); green ([[phospholipid]]s)]]
A '''lipoprotein''' is a [[biochemistry|biochemical]] assembly that contains both [[protein]]s and [[lipid]]s. The lipids or their derivatives may be covalently or non-covalently bound to the proteins. Many [[enzyme]]s, [[transporter]]s, structural proteins, [[antigen]]s, [[adhesin]]s and [[toxin]]s are lipoproteins. Examples include the [[High_density_lipoprotein|high density]] and [[Low_density_lipoprotein|low density]] lipoproteins of the [[blood]], the [[cytochrome|transmembrane proteins]] of the [[mitochondrion]] and the [[chloroplast]], and bacterial lipoproteins [http://www.mrc-lmb.cam.ac.uk/genomes/dolop/].
==Function==
The lipids are often an essential part of the complex, even if they seem to have no catalytic activity themselves. To isolate transmembrane lipoproteins from their associated [[Biological_membrane|membranes]], [[detergent]]s are often needed.
All [[cell (biology)|cell]]s use and rely on [[fat]]s and, for all [[animal]] cells, [[cholesterol]] as building blocks to create the multiple [[cell membrane|membrane]]s which cells use to both control internal water content, internal water soluble elements and to organize their internal structure and protein enzymatic systems.
Lipoproteins in the blood, an aqueous medium, carry fats around the body. The protein particles have [[hydrophilic]] groups aimed outward so as to attract water molecules; this makes them soluble in the salt water based blood pool. Triglyceride-fats and cholesterol are carried internally, shielded from the water by the protein particle.
The interaction of the proteins forming the surface of the particles with (a) enzymes in the blood, (b) with each other and (c) with specific proteins on the surfaces of cells determine whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles.
Regarding [[atheroma]] development and progression vs. regression, the key issue has always been cholesterol transport patterns, not cholesterol concentration itself.
==Classification==
===By density===
General categories of lipoproteins, listed in order from larger and less dense (more fat than protein) to smaller and more dense (more protein, less fat):
* [[Chylomicron]]s - carry [[triacylglycerol]] (fat) from the [[intestine]]s to the [[liver]], [[skeletal muscle]], and to [[adipose tissue]].
* [[Very low density lipoprotein]]s (VLDL) - carry (newly synthesised) [[triacylglycerol]] from the liver to adipose tissue.
* [[Intermediate density lipoprotein]]s (IDL) - are intermediate between VLDL and LDL. They are not usually detectable in the blood.
* [[Low density lipoprotein]]s (LDL) - carry cholesterol from the liver to cells of the body. Sometimes referred to as the "bad cholesterol" lipoprotein.
* [[High density lipoprotein]]s (HDL) - collects cholesterol from the body's tissues, and brings it back to the liver. Sometimes referred to as the "good cholesterol" lipoprotein.
===Alpha and beta===
It is also possible to classify lipoproteins as "alpha" and "beta", akin to the classification of proteins in [[serum protein electrophoresis]]. This terminology is sometimes used in describing lipid disorders such as [[Abetalipoproteinemia]].
===Lipoprotein(a)===
Lipoprotein(a) - Lp(a), Cardiology diagnostic tests
: Normal: <14mg/dL
: High risk: >19mg/dL
: How to lower: [[aerobic exercise]], [[niacin]], [[aspirin]], [[guggulipid]].
source: Beyond Cholesterol, Julius Torelli MD, 2005 ISBN 0-312-34863-0 p.91
==Metabolism==
The handling of lipoproteins in the body is referred to as lipoprotein metabolism. It is divided into two pathways, exogenous and endogenous, depending in large part on whether the lipoproteins in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous).
===Exogenous pathway===
[[Epithelial cell]]s lining the [[small intestine]] readily absorb lipids from the diet. These lipids, including triglycerides, phospholipids, and cholesterol, are assembled with [[apolipoprotein B-48]] into [[chylomicron]]s. These nascent chylomicrons are secreted from the intestinal epithelial cells into the [[lymphatic circulation]] in a process that depends heavily on apolipoprotein B-48. As they circulate through the lymphatic vessels, nascent chylomicrons bypass the liver circulation and are drained elsewhere into the bloodstream.
In the bloodstream, HDL particles donate [[apolipoprotein C-II]] and [[apolipoprotein E]] to the nascent chylomicron; the chylomicron is now considered mature. Via apolipoprotein C-II, mature chylomicrons activate [[lipoprotein lipase]] (LPL), an enzyme on [[endothelial cell]]s lining the blood vessels. LPL catalyzes a [[hydrolysis]] reaction that ultimately releases [[glycerol]] and [[fatty acid]]s from the chylomicrons. Glycerol and fatty acids can be absorbed in peripheral tissues, especially [[adipose]] and [[muscle]], for energy and storage.
The hydrolyzed chylomicrons are now considered chylomicron remnants. The chylomicron remnants continue circulating until they interact via apolipoprotein E with [[chylomicron remnant receptor]]s, found chiefly in the liver. This interaction causes the [[endocytosis]] of the chylomicron remnants, which are subsequently hydrolyzed within [[lysosome]]s. Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use.
===Endogenous pathway===
The liver is another important source of lipoproteins, principally VLDL. Triacylglycerol and cholesterol are assembled with [[apolipoprotein B-100]] to form VLDL particles. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100.
As in chylomicron metabolism, the [[apolipoprotein C-II]] and [[apolipoprotein E]] of VLDL particles are acquired from HDL particles. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature.
Again like chylomicrons, VLDL particles circulate and encounter LPL expressed on endothelial cells. Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by preipheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or [[intermediate density lipoprotein]]s (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by [[hepatic lipase]].
Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants, called [[low density lipoprotein]]s (LDL), which contain a relatively high cholesterol content. LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the [[LDL receptor]] and apolipoprotein B-100 or E on the LDL molecule. Absorption occurs through [[endocytosis]], and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.
==See also==
* [[Apolipoprotein]]
* [[Lipid anchored protein]]
* [[Lipid anchor]]
==External links==
* [http://www.mrc-lmb.cam.ac.uk/genomes/dolop/ Database of bacterial lipoproteins at mrc-lmb.cam.ac.uk]
* [http://courses.washington.edu/conj/membrane/lipoprotein.htm Overview and diagram at washington.edu]
* [http://www.biochem.wisc.edu/attie/research/researchLDLR.html Lipoprotein assembly at wisc.edu]
* [http://people.pharmacy.purdue.edu/~dallen/lipo.html Lipoprotein circulation at purdue.edu]
* {{MeshName|Lipoproteins}}
* {{MeshName|Proteolipids}}
{{Membrane lipids}}
{{Lipoproteins}}
[[Category:Lipids]]
[[Category:Lipoproteins|*]]
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