Cholesterol

Jan 12, 2012 06:27 PM

Cholesterol, from the <a title="Greek language" href="/wiki/Greek_language">Greek</a> chole- (<a title="Bile" href="/wiki/Bile">bile</a>) and stereos (solid) followed by the <a class="mw-redirect" title="Chemical" href="/wiki/Chemical">chemical</a> <a title="Suffix" href="/wiki/Suffix">suffix</a> -ol for an alcohol, is an <a title="Organic compound" href="/wiki/Organic_compound">organic</a> <a title="Chemical substance" href="/wiki/Chemical_substance">chemical substance</a> classified as a waxy <a title="Steroid" href="/wiki/Steroid">steroid</a> of fat

For a person of about 68 kg (150 pounds), typical total body cholesterol synthesis is about 1 g (1,000 mg) per day, and total body content is about 35 g. Typical daily additional dietary intake in the United States is 200–300 mg.[<a title="Wikipedia:Citation needed" href="/wiki/Wikipedia:Citation_needed">citation needed</a>] The body compensates for cholesterol intake by reducing the amount synthesized.

Through the interaction with the phospholipid fatty acid chains, cholesterol increases membrane packing, which reduces membrane fluidity.<a href="#cite_note-isbn1-4292-4646-4-4">[5]</a> In this structural role, cholesterol reduces the permeability of the plasma membrane to neutral solutes,<a href="#cite_note-pmid1664240-5">[6]</a> protons, (positive <a title="Hydrogen" href="/wiki/Hydrogen">hydrogen</a> ions) and <a class="mw-redirect" title="Sodium ion" href="/wiki/Sodium_ion">sodium ions</a>

<h3>Dietary sources</h3>

<a title="Animal fat" href="/wiki/Animal_fat">Animal fats</a> are complex mixtures of <a title="Triglyceride" href="/wiki/Triglyceride">triglycerides</a>, with lesser amounts of <a title="Phospholipid" href="/wiki/Phospholipid">phospholipids</a> and cholesterol. As a consequence, all foods containing animal fat contain cholesterol to varying extents.<a href="#cite_note-isbn0-9531949-5-7-10">[11]</a> Major dietary sources of cholesterol include <a title="Cheese" href="/wiki/Cheese">cheese</a>, <a title="Egg yolk" href="/wiki/Egg_yolk">egg yolks</a>, <a title="Beef" href="/wiki/Beef">beef</a>, <a title="Pork" href="/wiki/Pork">pork</a>, <a title="Poultry" href="/wiki/Poultry">poultry</a>, <a title="Fish" href="/wiki/Fish">fish</a>, and <a title="Shrimp" href="/wiki/Shrimp">shrimp</a>.<a href="#cite_note-USDA-11">[12]</a> Human <a class="mw-redirect" title="Breast milk" href="/wiki/Breast_milk">breast milk</a> also contains significant quantities of cholesterol.<a href="#cite_note-ajcn-breastmilk-12">[13]</a>

<h3>Regulation of cholesterol synthesis</h3>

Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the <a title="Homeostasis" href="/wiki/Homeostasis">homeostatic</a> mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, whereas lower intake from food has the opposite effect...

Since cholesterol is insoluble in blood, it is transported in the circulatory system within <a title="Lipoprotein" href="/wiki/Lipoprotein">lipoproteins</a>, complex discoidal particles that have an exterior composed of <a title="Amphiphile" href="/wiki/Amphiphile">amphiphilic</a> proteins and lipids whose outward-facing surfaces are water-soluble and inward-facing surfaces are lipid-soluble; <a class="mw-redirect" title="Triglycerides" href="/wiki/Triglycerides">triglycerides</a> and cholesterol esters are carried internally. Phospholipids and cholesterol, being amphipathic, are transported in the surface monolayer of the lipoprotein particle.

In addition to providing a soluble means for transporting cholesterol through the blood, lipoproteins have cell-targeting signals that direct the lipids they carry to certain tissues. For this reason, there are several types of lipoproteins within blood called, in order of increasing density, <a title="Chylomicron" href="/wiki/Chylomicron">chylomicrons</a>, <a class="mw-redirect" title="Very-low-density lipoprotein" href="/wiki/Very-low-density_lipoprotein">very-low-density lipoprotein</a> (VLDL), <a title="Intermediate-density lipoprotein" href="/wiki/Intermediate-density_lipoprotein">intermediate-density lipoprotein</a> (IDL), <a title="Low-density lipoprotein" href="/wiki/Low-density_lipoprotein">low-density lipoprotein</a> (LDL), and <a title="High-density lipoprotein" href="/wiki/High-density_lipoprotein">high-density lipoprotein</a> (HDL). The more lipid and less protein a lipoprotein has the less dense it is.

Chylomicrons are the transporters that carry fats from the intestine to muscle and other tissues that need fatty acids for energy or fat production. Cholesterol that is not used by muscles remains in more cholesterol-rich chylomicron remnants, which are taken up from the bloodstream by the liver..

VLDL molecules are produced by the liver and contain excess triacylglycerol and cholesterol that is not required by the liver for synthesis of bile acids. These molecules contain <a class="mw-redirect" title="Apolipoprotein B100" href="/wiki/Apolipoprotein_B100">apolipoprotein B100</a> and apolipoprotein E in their shells

the other half continue to lose triacylglycerols in the bloodstream until they form LDL molecules, which have the highest percentage of cholesterol within them...

LDL molecules, therefore, are the major carriers of cholesterol in the blood, and each one contains approximately 1,500 molecules of cholesterol ester. The shell of the LDL molecule contains just one molecule of apolipoprotein B100, which is recognized by the <a title="LDL receptor" href="/wiki/LDL_receptor">LDL receptor</a> in peripheral tissues. Upon binding of apolipoprotein B100, many LDL receptors become localized in <a title="Clathrin" href="/wiki/Clathrin">clathrin</a>-coated pits. Both the LDL and its receptor are internalized by <a title="Endocytosis" href="/wiki/Endocytosis">endocytosis</a> to form a vesicle within the cell. The vesicle then fuses with a <a title="Lysosome" href="/wiki/Lysosome">lysosome</a>, which has an enzyme called <a title="Lysosomal lipase" href="/wiki/Lysosomal_lipase">lysosomal acid lipase</a> that hydrolyzes the cholesterol esters. Now within the cell, the cholesterol can be used for membrane biosynthesis or esterified and stored within the cell, so as to not interfere with cell membranes.

Synthesis of the LDL receptor is regulated by <a class="mw-redirect" title="SREBP" href="/wiki/SREBP">SREBP</a>, the same regulatory protein as was used to control synthesis of cholesterol de novo in response to cholesterol presence in the cell. When the cell has abundant cholesterol, LDL receptor synthesis is blocked so new cholesterol in the form of LDL molecules cannot be taken up. On the converse, more LDL receptors are made when the cell is deficient in cholesterol. When this system is deregulated, many LDL molecules appear in the blood without receptors on the peripheral tissues. These LDL molecules are oxidized and taken up by <a class="mw-redirect" title="Macrophages" href="/wiki/Macrophages">macrophages</a>, which become engorged and form foam cells. These cells often become trapped in the walls of blood vessels and contribute to <a title="Atheroma" href="/wiki/Atheroma">artherosclerotic plaque</a> formation. Differences in cholesterol homeostasis affect the development of early atherosclerosis (carotid intima-media thickness).<a href="#cite_note-pmid20976107-28">[29]</a> These plaques are the main causes of heart attacks, strokes, and other serious medical problems, leading to the association of so-called LDL cholesterol (actually a <a title="Lipoprotein" href="/wiki/Lipoprotein">lipoprotein</a>) with "bad" cholesterol.<a href="#cite_note-isbn0-7167-4955-6-27">[28]</a>

Also, HDL particles are thought to transport cholesterol back to the liver for excretion or to other tissues that use cholesterol to synthesize hormones in a process known as <a title="Reverse cholesterol transport" href="/wiki/Reverse_cholesterol_transport">reverse cholesterol transport</a> (RCT).<a href="#cite_note-pmid15976321-29">[30]</a> Having large numbers of large HDL particles correlates with better health outcomes.<a href="#cite_note-pmid2642759-30">[31]</a> In contrast, having small numbers of large HDL particles is independently associated with <a title="Atheroma" href="/wiki/Atheroma">atheromatous</a> disease progression within the arteries

Cholesterol

Attachments