Editing Lipoprotein (section)

== Functions ==

=== Metabolism ===
The handling of lipoprotein particles in the body is referred to as ''lipoprotein particle metabolism''. It is divided into two pathways, [[exogenous]] and [[endogenous]], depending in large part on whether the lipoprotein particles in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous), through [[de novo synthesis]] of triglycerides.

The [[hepatocyte]]s are the main platform for the handling of triglycerides and cholesterol; the liver can also store certain amounts of [[glycogen]] and triglycerides. While [[adipocyte]]s are the main storage cells for triglycerides, they do not produce any lipoproteins.

====Exogenous pathway====
[[File:Lipoprotein metabolism.png|500px|thumbnail|right|Simplified flowchart showing the essentials of lipoprotein metabolism.]]

[[Bile]] emulsifies fats contained in the [[chyme]], then [[pancreatic lipase]] cleaves triglyceride molecules into two fatty acids and one 2-monoacylglycerol. [[Enterocyte]]s readily absorb the small molecules from the chymus. Inside of the enterocytes, fatty acids and [[monoacylglyceride]]s are transformed again into triglycerides. Then these lipids are assembled with [[apolipoprotein B-48]] into ''nascent [[chylomicron]]s''. These particles are then secreted into the [[lacteal]]s 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 via the [[thoracic duct]] into the bloodstream.

In the blood stream, ''nascent chylomicron particles'' interact with HDL particles, resulting in HDL donation of [[apolipoprotein C-II]] and [[apolipoprotein E]] to the nascent chylomicron. The chylomicron at this stage is then considered mature. Via apolipoprotein C-II, mature chylomicrons activate [[lipoprotein lipase]] (LPL), an enzyme on [[endothelial cell]]s lining the blood vessels. LPL catalyzes the [[hydrolysis]] of triglycerides that ultimately releases glycerol and [[fatty acid]]s from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially [[Adipose tissue|adipose]] and [[Muscle tissue|muscle]], for energy and storage.

The hydrolyzed chylomicrons are now called ''chylomicron remnants''. The chylomicron remnants continue circulating the bloodstream until they interact via apolipoprotein E with chylomicron remnant receptors, 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 the central platform for the handling of lipids: it is able to store glycerols and fats in its cells, the [[hepatocytes]]. Hepatocytes are also able to create triglycerides via de novo synthesis. They also produce the bile from cholesterol. The intestines are responsible for absorbing cholesterol. They transfer it over into the blood stream.

In the hepatocytes, triglycerides and cholesteryl esters are assembled with [[apolipoprotein B-100]] to form ''nascent VLDL particles''. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100.

In the blood stream, ''nascent VLDL particles'' bump with HDL particles; as a result, HDL particles donate [[apolipoprotein C-II]] and apolipoprotein E to the nascent VLDL particle. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature. VLDL particles circulate and encounter LPL expressed on [[endothelial cell]]s. 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 peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called [[Remnant cholesterol|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<ref name="pmid21573056">{{cite journal | vauthors = Kumar V, Butcher SJ, Öörni K, Engelhardt P, Heikkonen J, Kaski K, Ala-Korpela M, Kovanen PT | title = Three-dimensional cryoEM reconstruction of native LDL particles to 16Å resolution at physiological body temperature | journal = PLOS ONE | volume = 6 | issue = 5 | pages = e18841 | date = May 2011 | pmid = 21573056 | pmc = 3090388 | doi = 10.1371/journal.pone.0018841 | bibcode = 2011PLoSO...618841K | doi-access = free }}</ref> ({{YouTube|id=CtFwss81GBk|title=see native LDL structure at 37°C}}). 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 on the LDL particle. Absorption occurs through [[endocytosis]], and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.

=== Possible role in oxygen transport ===
Plasma lipoproteins may carry oxygen gas.<ref>{{Cite journal|last1=Petyaev|first1=I. M.|last2=Vuylsteke|first2=A.|last3=Bethune|first3=D. W.|last4=Hunt|first4=J. V.|date=1998|title=Plasma oxygen during cardiopulmonary bypass: a comparison of blood oxygen levels with oxygen present in plasma lipid|journal=Clinical Science |volume=94|issue=1|pages=35–41|doi=10.1042/cs0940035|issn=0143-5221|pmid=9505864}}</ref> This property is due to the crystalline hydrophobic structure of lipids, providing a suitable environment for O<sub>2</sub> solubility compared to an aqueous medium.<ref>{{Cite journal|last1=Bacić|first1=G.|last2=Walczak|first2=T.|last3=Demsar|first3=F.|last4=Swartz|first4=H. M.|date=October 1988|title=Electron spin resonance imaging of tissues with lipid-rich areas|journal=Magnetic Resonance in Medicine|volume=8|issue=2|pages=209–219|doi=10.1002/mrm.1910080211|issn=0740-3194|pmid=2850439|s2cid=41810978}}</ref>

=== Role in inflammation ===
[[Inflammation]], a biological system response to stimuli such as the introduction of a [[pathogen]], has an underlying role in numerous systemic biological functions and pathologies. This is a useful response by the immune system when the body is exposed to pathogens, such as bacteria in locations that will prove harmful, but can also have detrimental effects if left unregulated. It has been demonstrated that lipoproteins, specifically HDL, have important roles in the inflammatory process.<ref name=":0">{{cite journal | vauthors = Namiri-Kalantari R, Gao F, Chattopadhyay A, Wheeler AA, Navab KD, Farias-Eisner R, Reddy ST | title = The dual nature of HDL: Anti-Inflammatory and pro-Inflammatory | journal = BioFactors | volume = 41 | issue = 3 | pages = 153–9 | date = May 2015 | pmid = 26072738 | doi = 10.1002/biof.1205 | s2cid = 28785539 }}</ref>

When the body is functioning under normal, stable physiological conditions, HDL has been shown to be beneficial in several ways.<ref name=":0" /> LDL contains apolipoprotein B (apoB), which allows LDL to bind to different tissues, such as the artery wall if the [[glycocalyx]] has been damaged by high [[blood sugar level]]s.<ref name=":0" /> If oxidised, the LDL can become trapped in the proteoglycans, preventing its removal by HDL cholesterol efflux.<ref name=":0" /> Normal functioning HDL is able to prevent the process of oxidation of LDL and the subsequent inflammatory processes seen after oxidation.<ref name=":0" />

[[Lipopolysaccharide]], or LPS, is the major pathogenic factor on the cell wall of [[Gram-negative bacteria]]. [[Gram-positive bacteria]] has a similar component named [[Lipoteichoic acid]], or LTA. HDL has the ability to bind LPS and LTA, creating HDL-LPS complexes to neutralize the harmful effects in the body and clear the LPS from the body.<ref name=":1">{{cite book | vauthors = Pirillo A, Catapano AL, Norata GD | title = High Density Lipoproteins | chapter = HDL in infectious diseases and sepsis | series = Handbook of Experimental Pharmacology | volume = 224 | pages = 483–508 | date = 2015 | publisher = Springer | pmid = 25522999 | doi = 10.1007/978-3-319-09665-0_15 | hdl = 2434/274561 | isbn = 978-3-319-09664-3 }}</ref> HDL also has significant roles interacting with cells of the immune system to modulate the availability of cholesterol and modulate the immune response.<ref name=":1" />

Under certain abnormal physiological conditions such as system [[infection]] or [[sepsis]], the major components of HDL become altered,<ref name=":1" /><ref name=":2">{{cite journal | vauthors = Norata GD, Pirillo A, Ammirati E, Catapano AL | title = Emerging role of high density lipoproteins as a player in the immune system | journal = Atherosclerosis | volume = 220 | issue = 1 | pages = 11–21 | date = January 2012 | pmid = 21783193 | doi = 10.1016/j.atherosclerosis.2011.06.045 }}</ref> The composition and quantity of lipids and apolipoproteins are altered as compared to normal physiological conditions, such as a decrease in HDL cholesterol (HDL-C), phospholipids, apoA-I (a major lipoprotein in HDL that has been shown to have beneficial anti-inflammatory properties), and an increase in [[Serum amyloid A]].<ref name=":1" /><ref name=":2" /> This altered composition of HDL is commonly referred to as acute-phase HDL in an acute-phase inflammatory response, during which time HDL can lose its ability to inhibit the oxidation of LDL.<ref name=":0" /> In fact, this altered composition of HDL is associated with increased mortality and worse clinical outcomes in patients with sepsis.<ref name=":1" />