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| __NOTOC__
| | #Redirect [[High density lipoprotein physiology]] |
| {{High density lipoprotein}}
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| {{CMG}}; {{AE}} {{AN}}; {{RT}}
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| ==Overview==
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| ==Biochemistry==
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| ===Structure===
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| {| class="wikitable" border="1" style="background:FloralWhite"
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| | '''Lipoprotein'''|| '''Density''' || '''Size'''|| '''% Protein'''|| '''% Cholesterol'''|| '''% Triglyceride'''|| '''Major Lipid'''|| '''Apolipoprotein'''
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| * HDL are the smallest of the lipoproteins. They are the densest because they contain the highest proportion of [[protein]]. They contain the A class of [[apolipoprotein]]s.
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| * The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipids, which resemble cholesterol-free flattened spherical lipoprotein particles. They are capable of picking up cholesterol from cells they interact with.
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| * A [[Blood plasma|plasma]] enzyme called [[lecithin-cholesterol acyltransferase]] (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol) which is then sequestered into the core of the lipoprotein particle eventually making the newly synthesized HDL spherical. They increase in size as they circulate through the bloodstream and incorporate more cholesterol molecules into their structure.
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| * Thus it is the concentration of large HDL particles which more accurately reflects protective action, as opposed to the concentration of total HDL particles.<ref>Kwiterovich PO. The Metabolic Pathways of High-Density Lipoprotein, Low-Density Lipoprotein, and Triglycerides: A Current Review. Am J Cardiol 2000;86(suppl):5L.</ref> This ratio of large HDL to total HDL particles varies widely and is only measured by more sophisticated lipoprotein assays using either [[electrophoresis]], originally developed in the 1970s, or newer [[Nuclear magnetic resonance|Nuclear magnetic resonance]] (NMR) spectroscopy which was developed in the 1990s.
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| * HDL particles are not inherently protective. It is only the HDL particles which become the largest (actually picking up and carrying cholesterol) which are protective. There is no reliable relationship between total HDL and large HDL, and more sophisticated analyses which actually measure large HDL, not just total, correlate much better with clinical outcomes.<ref name="pmid23488589">{{cite journal |author=Tran-Dinh A, Diallo D, Delbosc S, ''et al.'' |title=HDL and endothelial protection |journal=[[British Journal of Pharmacology]] |volume= |issue= |pages= |year=2013 |month=March |pmid=23488589 |doi=10.1111/bph.12174 |url=}}</ref>
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| ==HDL Receptors==
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| ==Enzymes Associated with HDL==
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| ===HDL Metabolism===
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| * As mentioned above, the HDL is synthesized in liver and intestines as small nascent particles, composed mainly of [[phospholipids]] and [[apolipoproteins]].
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| * As it travels in the blood it acquires surface components, like more phospholipids, cholesterol and apolipoproteins, from [[triglyceride]] depleted [[chylomicron]]s and remnants of [[VLDL]].
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| * As this initial HDL particle contains less amounts of cholesterol, it acquires free unesterified cholesterol from tissues of the liver and arterial walls. This hydrophobic free cholesterol sinks into the center of the HDL particle. The [[Apolipoprotein A1]] acts as a signal protein in mobilizing cholesterol esters from within the cells.
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| * In the peripheral tissues, the nascent HDL particles interact with a cell surface protein called ABCA1 (also known as cholesterol efflux regulatory protein, CERP). High cholesterol levels induce expression of ABCA1 gene and production of the protein. Mutations of this transport protein gene causes familial HDL deficiencies and [[Tangier disease]]. The HDL also accepts cholesterol from triglycerides that has undergone lipolysis.
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| * Once the cholesterol is acquired by the nascent HDL particles from the peripheral tissues, it gets esterified by a plasma enzyme [[LCAT]] (Lecithin-cholesterol acyltransferase). This enzyme is activated by [[apolipoprotein A1 ]].
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| ====Cholesterol Ester Transfer Protein (CETP)====
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| * This protein mediates exchange of cholesterol between HDL particles, and [[triglyceride]] rich [[LDL]] and [[VLDL]] in both directions.
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| * It is normally present in both periphery and liver and functions to channel cholesterol to the liver for uptake and metabolism.
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| ==References==
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| {{Reflist|2}}
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| [[Category:Lipid disorders]]
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| [[Category:Cardiology]]
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| [[Category:Lipoproteins]]
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