"කොලෙස්ටරෝල්" හි සංශෝධන අතර වෙනස්කම්

The name cholesterol originates from the [[Greek language|Greek]] ''chole-'' ([[bile]]) and ''stereos'' (solid), and the [[chemical]] [[suffix]] ''-ol'' for an alcohol, as François Poulletier de la Salle first identified cholesterol in solid form in [[gallstone]]s, in 1769. However, it was only in 1815 that chemist [[Michel Eugène Chevreul|Eugène Chevreul]] named the compound "cholesterine".<ref>{{cite journal |author=Olson RE |title=Discovery of the lipoproteins, their role in fat transport and their significance as risk factors |journal=J. Nutr. |volume=128 |issue=2 Suppl |pages=439S–443S |year=1998 |pmid=9478044 |url=http://jn.nutrition.org/cgi/content/full/128/2/439S |month=Feb |day=01}}</ref>

 

Cholesterol is required to build and maintain [[cell membrane]]s; it regulates [[membrane fluidity]] over a wide range of [[temperature]]s. The liver produces about 1 gram of cholesterol per day, in bile. The [[hydroxyl]] group on cholesterol interacts with the [[Polar molecules|polar]] head groups of the [[lipid bilayer|membrane]] [[Phospholipid|phospholipids]] and [[sphingolipid]]s, while the bulky [[steroid]] and the [[hydrocarbon]] chain is embedded in the membrane, alongside the [[Polar molecules#Non-polar molecules|nonpolar]] [[Fatty acid|fatty acid chains]] of the other lipids. Some research indicates that cholesterol may act as an [[antioxidant]].<ref name=Smith1991>{{cite journal |author=Smith LL |title=Another cholesterol hypothesis: cholesterol as antioxidant |journal=Free Radic. Biol. Med. |volume=11 |issue=1 |pages=47–61 |year=1991 |pmid=1937129 |doi=10.1016/0891-5849(91)90187-8}}</ref> [[Bile]], which is stored in the [[gallbladder]] and helps digest fats, is important for the absorption of the [[fat soluble vitamins]], vitamins [[vitamin A|A]], [[vitamin D|D]], [[vitamin E|E]], and [[vitamin K|K]]. It is the main precursor of [[vitamin D]] and of the [[steroid hormone]]s, which include [[cortisol]] and [[aldosterone]] (in the [[adrenal gland]]s) and [[progesterone]], [[estrogen]]s, and [[testosterone]] (the sex hormones), and their derivatives. It provides the basic structure of all the steroids. In myelin, it envelopes and insulates nerves, helping greatly to conduct nerve impulses.

 

Cholesterol is essential for the structure and function of invaginated [[caveolae]] and clathrin-coated pits, including caveola-dependent and clathrin-dependent [[endocytosis]]. The role of cholesterol in such endocytosis can be investigated by using [[methyl beta cyclodextrin]] (MβCD) to remove cholesterol from the plasma membrane.

 

Most of the cholesterol in the body is synthesized therein; some is absorbed in the diet. Cholesterol is more abundant in tissues which either synthesize more, or have more abundant, densely-packed membranes, for example, the [[liver]], [[spinal cord]] and [[brain]]. It plays a central role in many [[biochemistry|biochemical]] processes, such as the building of cell membranes and the synthesis of [[steroid hormone]]s.<ref>{{cite book |last=Stryer |first=Lubert |title=Biochemistry |edition=4th ed. |year=1995|publisher=W.H. Freeman & co. |location=New York |isbn=0-7167-2009-4 |pages= 280, 703}}</ref>

 

[[Konrad Bloch]] and [[Feodor Lynen]] shared the [[Nobel Prize in Physiology or Medicine]] in 1964 for their discoveries concerning the mechanism and regulation of cholesterol and [[fatty acid]] metabolism.

 

{{Seealso|Blood lipids}}

Since cholesterol is insoluble in blood, it is transported in the circulatory system within [[lipoprotein]]s, complex spherical particles which have an exterior composed of [[amphiphile|amphiphilic]] proteins and lipids whose outward-facing surface is water-soluble and inward-facing surfaces are lipid-soluble; [[lipid|fats]] and cholesterol esters are carried internally. There is a large range of lipoproteins within blood, generally called, from larger to smaller size: [[chylomicron]]s, [[very low density lipoprotein]] (VLDL), [[intermediate density lipoprotein]] (IDL), [[low density lipoprotein]] (LDL) and [[high density lipoprotein]] (HDL). The cholesterol within all the various lipoproteins is identical although some cholesterol is carried as the "free" alcohol and some is carried as fatty acyl esters referred to as cholesterol esters.

On the other hand, [[high-density lipoprotein]] (HDL) particles are thought to transport cholesterol back to the liver for excretion in a process known as reverse cholesterol transport (RCT).<ref>{{cite journal |author=Lewis GF and Rader DJ. | title=New insights into the regulation of HDL metabolism and reverse cholesterol transport | journal=Circ. Res. | volume=96 |issue=12 |pages=1221–1232 |year=2005 |pmid=15976321 |doi=10.1161/01.RES.0000170946.56981.5c}}</ref> Having large numbers of large HDL particles correlates with better health outcomes.<ref>{{cite journal | author=Gordon DJ, Probstfield JL, ''et al''. | title=High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies | journal=Circulation | volume=79 | issue=1 | pages=8–15 | year=1989 | pmid=2642759 |doi=}}</ref> In contrast, having small numbers of large HDL particles is independently associated with [[atheroma]]tous disease progression within the arteries.

 

Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the [[homeostasis|homeostatic]] mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, while lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of [[intracellular]] cholesterol in the [[endoplasmic reticulum]] by the [[protein]] [[Sterol regulatory element binding protein|SREBP]] (Sterol Regulatory Element Binding Protein 1 and 2).<ref name="pmid17666007">{{cite journal | author = Espenshade PJ, Hughes AL | title = Regulation of sterol synthesis in eukaryotes | journal = Annu. Rev. Genet. | volume = 41 | issue = | pages = 401–27 | year = 2007 | pmid = 17666007 | doi = 10.1146/annurev.genet.41.110306.130315 | url = | issn = }}</ref> In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP-cleavage activating protein) and [[Insig1]]. When cholesterol levels fall, Insig-1 dissociates from the SREBP-SCAP complex, allowing the complex to migrate to the [[Golgi apparatus]], where SREBP is cleaved by S1P and S2P (site-1 and -2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and acts as a [[transcription factor]] to bind to the [[Sterol regulatory element|SRE]] (sterol regulatory element) of a number of genes to stimulate their [[Transcription (genetics)|transcription]]. Among the genes transcribed are the [[LDL receptor]] and [[HMG-CoA reductase pathway|HMG-CoA reductase]]. The former scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase of endogenous production of cholesterol.<ref>{{cite journal | author=Brown MS, Goldstein JL | title=The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor | year=1997 | journal=Cell | volume=89 | pages=331 | pmid=9150132 | doi=10.1016/S0092-8674(00)80213-5 | url=http://www.cell.com/content/article/abstract?uid=PIIS0092867400802135}}</ref>

 

A large part of this signaling pathway was clarified by Dr. [[Michael S. Brown]] and Dr. [[Joseph L. Goldstein]] in the 1970s. In 1985, they received the [[Nobel Prize in Physiology or Medicine]] for their work. Their subsequent work shows how the SREBP pathway regulates expression of many genes that control lipid formation and metabolism and body fuel allocation.

 

Cholesterol is oxidized by the liver into a variety of [[bile acids]]. These in turn are [[phase 2 reaction|conjugated]] with [[glycine]], [[taurine]], [[glucuronic acid]], or [[sulfate]]. A mixture of conjugated and non-conjugated bile acids along with cholesterol itself is excreted from the [[liver]] into the [[bile]]. Approximately 95% of the bile acids are reabsorbed from the intestines and the remainder lost in the feces.<ref name="pmid12529265">{{cite journal | author = Wolkoff AW, Cohen DE | title = Bile acid regulation of hepatic physiology: I. Hepatocyte transport of bile acids | journal = Am. J. Physiol. Gastrointest. Liver Physiol. | volume = 284 | issue = 2 | pages = G175–9 | year = 2003 | month = February | pmid = 12529265 | doi = 10.1152/ajpgi.00409.2002 | url = | issn = }}</ref> The excretion and reabsorption of bile acids forms the basis of the [[enterohepatic circulation]] which is essential for the digestion and absorption of dietary fats. Under certain circumstances, when more concentrated, as in the [[gallbladder]], cholesterol crystallises and is the major constituent of most [[gallstone]]s, although [[lecithin]] and [[bilirubin]] gallstones also occur less frequently.

 

[[Animal fat]]s are complex mixtures of [[triglyceride]]s, with lesser amounts of [[phospholipid]]s and cholesterol. Consequently all foods containing animal fat contain cholesterol to varying extents.<ref name=Christie>{{cite book |last = Christie | first = W. W. | coauthors = | title = Lipid analysis | issue=3 | publisher = PJ Barnes and associates | year = 2003 | pages=416 | isbn=0-9531949-5-7}}</ref> Cholesterol is not present in plant based food sources unless it has been added during the food's preparation.<ref name=USDA>{{cite web | last = | first = | title = USDA National Nutrient Database for Standard Reference, Release 21 | publisher = United States Department of Agriculture | url = http://www.nal.usda.gov/fnic/foodcomp/Data/SR21/nutrlist/sr21w601.pdf | format=PDF | accessdate = 2008-10-24}}</ref> However plant products such as [[flax seed]]s and [[peanut]]s contain healthy cholesterol-like compounds called [[phytosterols]], which are suggested to help lower [[serum]] cholesterol levels.<ref name=ostlund2003>{{cite journal | author=Ostlund RE, Racette, SB, and Stenson WF | title=Inhibition of cholesterol absorption by phytosterol-replete wheat germ compared with phytosterol-depleted wheat germ | journal=Am J Clin Nutr | year=2003 | pages=1385–1589 | volume=77 | issue=6 |pmid=12791614}}</ref> Major dietary sources of cholesterol include [[cheese]], [[egg yolk]]s, [[beef]], [[pork]], [[poultry]], and [[shrimp]].<ref name=USDA/> Human [[breast milk]] also contains significant quantities of cholesterol.<ref name=ajcn-breastmilk>{{cite journal | author=Jensen RG, Hagerty MM, McMahon KE | title=Lipids of human milk and infant formulas: a review | journal=Am J Clin Nutr | year=1978 | pages=990–1016 | volume=31 | pmid=352132 | url=http://www.ajcn.org/cgi/reprint/31/6/990 | format=PDF | issue=6 | month=Jun | day=01}}</ref>

 

Dietary cholesterol plays a smaller role in blood cholesterol levels in comparison to fat intake. A number of measures can be taken to reduce blood cholesterol levels through changes in lifestyle, one of which is a change in diet. [[Trans fat|Trans]] and [[saturated fat]]s are significant contributors to elevated cholesterol levels in the blood stream. Avoiding animal products may decrease the cholesterol levels in the body not through dietary cholesterol reduction alone, but primarily through a reduced saturated fat intake. Those wishing to reduce their cholesterol through a change in diet should aim to consume less than 7% of their daily [[calorie]]s from saturated fat and less than 200mg of cholesterol per day.<ref>{{cite web | last = | first = | title = High blood cholesterol: what you need to know | publisher = National cholesterol education program | url =http://www.nhlbi.nih.gov/health/public/heart/chol/wyntk.htm | accessdate = 2008-10-24}}</ref>

 

=== Hypercholesterolemia ===

{{මූලික|hypercholesterolemia|lipid hypothesis}}

Some cholesterol derivatives, (among other simple cholesteric lipids) are known to generate the [[liquid crystal]]line ''cholesteric phase''. The cholesteric phase is in fact a [[chirality (chemistry)|chiral]] [[Liquid crystal|nematic phase]], and changes colour when its temperature changes. Therefore, cholesterol derivatives are commonly used in liquid crystal [[thermometer]]s and temperature-sensitive paints.

 

* [[Triglyceride]]s

* [[Diet and heart disease]]

* [[Niemann Pick disease]] Type C

 

<gallery>

Image:Steroidogenesis.svg|[[Steroidogenesis]]

</gallery>

 

{{Reflist|2}}

 

* [http://www.nhlbi.nih.gov/guidelines/cholesterol/ Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults] US National Institutes of Health Adult Treatment Panel III

* [http://www.fao.org/docrep/V4700E/V4700E08.htm Aspects of fat digestion and metabolism – UN/WHO Report 1994]