Просмотр кода страницы Английская Википедия:Cholesterol

{{Английская Википедия/Панель перехода}}
{{Short description|Sterol biosynthesized by all animal cells}}{{For|the journal|Cholesterol (journal)}}
{{Use dmy dates|date=August 2021}}
{{Chembox
| Watchedfields = changed
| verifiedrevid = 477165736
| ImageFile = Cholesterol.svg
| ImageSize = 280
| ImageAlt = Chemical structure of cholesterol
| ImageFile1 = Cholesterol-from-xtal-3D-bs.png
| ImageSize1 = 260
| ImageAlt1 = Ball-and-stick model of cholesterol
| ImageFile2 = Cholesterol-from-xtal-3D-sf.png
| ImageSize2 = 260
| ImageAlt2 = Space-filling model of cholesterol
| ImageFile3 = Sample of Cholesterol.jpg
| ImageSize3 = 200
| ImageAlt3 = Sample of Cholesterol
| IUPACName = Cholest-5-en-3β-ol
| SystematicName = (1''R'',3a''S'',3b''S'',7''S'',9a''R'',9b''S'',11a''R'')-9a,11a-Dimethyl-1-[(2''R'')-6-methylheptan-2-yl]-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1''H''-cyclopenta[''a'']phenanthren-7-ol
| OtherNames = Cholesterin, Cholesteryl alcohol<ref name=pubchem>{{cite web|title=Cholesterol, 57-88-5|url=https://pubchem.ncbi.nlm.nih.gov/compound/5997|publisher=PubChem, National Library of Medicine, US National Institutes of Health|date=9 November 2019|access-date=14 November 2019}}</ref>
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 2718
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 97C5T2UQ7J
| InChI = 1/C27H46O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h9,18-19,21-25,28H,6-8,10-17H2,1-5H3/t19-,21+,22+,23-,24+,25+,26+,27-/m1/s1
| InChIKey = HVYWMOMLDIMFJA-DPAQBDIFBB
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 112570
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C27H46O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h9,18-19,21-25,28H,6-8,10-17H2,1-5H3/t19-,21+,22+,23-,24+,25+,26+,27-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HVYWMOMLDIMFJA-DPAQBDIFSA-N
| CASNo =57-88-5
| CASNo_Ref = {{cascite|correct|CAS}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5775
| PubChem =5997
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00040
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 16113
| SMILES = C[C@H](CCCC(C)C)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
}}
|Section2={{Chembox Properties
| Formula =C<sub>27</sub>H<sub>46</sub>O
| MolarMass =386.65 g/mol
| Appearance = white crystalline powder<ref name=MSDS>{{cite web |url=http://physchem.ox.ac.uk/MSDS/CH/cholesterol.html |title=Safety (MSDS) data for cholesterol |access-date=2007-10-20 |archive-url=https://web.archive.org/web/20070712214801/http://physchem.ox.ac.uk/MSDS/CH/cholesterol.html |archive-date=12 July 2007 |url-status=dead }}</ref>
| Density = 1.052 g/cm<sup>3</sup>
| MeltingPtC = 148 to 150
| MeltingPt_ref =<ref name=MSDS/>
| BoilingPtC = 360
| BoilingPt_notes = (decomposes)
| Solubility = 0.095 mg/L (30&nbsp;°C)<ref name=pubchem/>
| SolubleOther = soluble in [[acetone]], [[benzene]], [[chloroform]], [[ethanol]], [[diethyl ether|ether]], [[hexane]], [[isopropyl myristate]], [[methanol]]
| MagSus = -284.2·10<sup>−6</sup> cm<sup>3</sup>/mol
 }}
|Section7={{Chembox Hazards
| MainHazards =
| FlashPt =209.3 ±12.4&nbsp;°C
| FlashPt_ref =
| AutoignitionPtC =
 }}
}}
{{Fats}}

'''Cholesterol''' is the principal [[sterol]] of all [[higher animals]], distributed in body tissues, especially the [[brain]] and [[spinal cord]], and in [[Animal fat|animal fats and oils]].<ref name="mlp">{{cite web |title=Cholesterol |url=https://medlineplus.gov/cholesterol.html |publisher=MedlinePlus, National Library of Medicine, US National Institutes of Health |access-date=23 August 2023 |date=10 December 2020}}</ref><ref>{{MeshName|Cholesterol|2013}}</ref>

Cholesterol is [[biosynthesis|biosynthesized]] by all animal [[Cell (biology)#Eukaryotic cells|cells]] and is an essential structural component of [[animal]] [[cell membrane]]s. In [[vertebrate]]s, [[hepatocyte|hepatic cells]] typically produce the greatest amounts. In the brain astrocytes produce cholesterol and transport it to neurons.<ref>{{cite journal |last1=Wang |first1=Hao |last2=Kulas |first2=Joshua A. |last3=Wang |first3=Chao |last4=Holtzman |first4=David M. |last5=Ferris |first5=Heather A. |last6=Hansen |first6=Scott B. |title=Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol |journal=Proceedings of the National Academy of Sciences |date=17 August 2021 |volume=118 |issue=33 |doi=10.1073/pnas.2102191118|pmid=34385305 |pmc=8379952 |bibcode=2021PNAS..11802191W |doi-access=free }}</ref> It is absent among [[prokaryote]]s ([[bacteria]] and [[archaea]]), although there are some exceptions, such as ''[[Mycoplasma]]'', which require cholesterol for growth.<ref>{{cite journal | vauthors = Razin S, Tully JG | title = Cholesterol requirement of mycoplasmas | journal = Journal of Bacteriology | volume = 102 | issue = 2 | pages = 306–110 | date = May 1970 | pmid = 4911537 | pmc = 247552 | doi = 10.1128/JB.102.2.306-310.1970 }}</ref> Cholesterol also serves as a [[Precursor (chemistry)|precursor]] for the [[biosynthesis]] of [[steroid hormone]]s, [[bile acid]]<ref name="Hanukoglu_1992">{{cite journal | vauthors = Hanukoglu I | title = Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 43 | issue = 8 | pages = 779–804 | date = December 1992 | pmid = 22217824 | doi = 10.1016/0960-0760(92)90307-5 | url = https://zenodo.org/record/890723 | s2cid = 112729 }}</ref> and [[vitamin D]].

Elevated levels of cholesterol in the blood, especially when bound to [[low-density lipoprotein]] (LDL, often referred to as "bad cholesterol"), may increase the risk of [[cardiovascular disease]].<ref name="Brunzell_2008" />

[[François Poulletier de la Salle]] first identified cholesterol in solid form in [[gallstone]]s in 1769. In 1815, chemist [[Michel Eugène Chevreul]] named the compound "cholesterine".<ref>{{cite journal | vauthors = Chevreul ME | date = 1816 | title = Recherches chimiques sur les corps gras, et particulièrement sur leurs combinaisons avec les alcalis. Sixième mémoire. Examen des graisses d'homme, de mouton, de boeuf, de jaguar et d'oie | trans-title = Chemical researches on fatty substances, and particularly on their combinations o filippos ine kapios with alkalis. Sixth memoir. Study of human, sheep, beef, jaguar and goose fat | language = French | journal = Annales de Chimie et de Physique | volume = 2 | pages = 339–372 [346] | url = https://books.google.com/books?id=DHCz1nhhYL8C&pg=PA346 | quote = Je nommerai ''cholesterine'', de χολη, bile, et στερεος, solide, la substance cristallisée des calculs biliares humains, ... | trans-quote = I will name ''cholesterine'' – from χολη (bile) and στερεος (solid) – the crystalized substance from human gallstones ... }}</ref><ref name="Olson_1998">{{cite journal | vauthors = Olson RE | title = Discovery of the lipoproteins, their role in fat transport and their significance as risk factors | journal = The Journal of Nutrition | volume = 128 | issue = 2 Suppl | pages = 439S–443S | date = February 1998 | pmid = 9478044 | doi = 10.1093/jn/128.2.439S | doi-access = free }}</ref>

== Etymology ==

The word ''cholesterol'' comes from [[Ancient Greek]] ''chole-'' '[[bile]]' and ''stereos'' 'solid', followed by the [[chemical]] [[suffix]] ''-ol'' for an [[Alcohol (chemistry)|alcohol]].

==Physiology==
Cholesterol is essential for all animal life. While most cells are capable of synthesizing it, the majority of cholesterol is ingested or synthesized by hepatocytes and transported in the blood to peripheral cells. The levels of cholesterol in peripheral tissues is dictated by a balance of uptake and export.<ref>{{cite journal |last1=Luo |first1=Jie |last2=Yang |first2=Hongyuan |last3=Song |first3=Bao-Liang |title=Mechanisms and regulation of cholesterol homeostasis |journal=Nature Reviews Molecular Cell Biology |date=April 2020 |volume=21 |issue=4 |pages=225–245 |doi=10.1038/s41580-019-0190-7|pmid=31848472 |s2cid=209392321 }}</ref> Under normal conditions, brain cholesterol is separate from peripheral cholesterol, i.e., the dietary and hepatic cholesterol do not cross the blood brain barrier. Rather, astrocytes produce and distribute cholesterol in the brain.<ref>{{cite journal |last1=Hansen |first1=Scott B. |last2=Wang |first2=Hao |title=The shared role of cholesterol in neuronal and peripheral inflammation |journal=Pharmacology & Therapeutics |date=September 2023 |volume=249 |pages=108486 |doi=10.1016/j.pharmthera.2023.108486|pmid=37390970 |s2cid=259303593 }}</ref>

De novo synthesis, both in astrocytes and hepatocytes, occurs by a complex 37-step process. This begins with the [[mevalonate]] or [[mevalonate pathway|HMG-CoA reductase pathway]], the target of [[statin]] drugs, which encompasses the first 18 steps. This is followed by 19 additional steps to convert the resulting [[lanosterol]] into cholesterol.<ref>{{Cite journal |last1=Bae |first1=Soo-Han |last2=Lee |first2=Joon No |last3=Fitzky |first3=Barbara U. |last4=Seong |first4=Jekyung |last5=Paik |first5=Young-Ki |date=May 1999 |title=Cholesterol Biosynthesis from Lanosterol |url=https://www.jbc.org/article/S0021-9258(19)73136-6/fulltext |journal=[[Journal of Biological Chemistry]] |volume=274 |issue=21 |pages=14624–14631 |doi=10.1074/jbc.274.21.14624 |pmid=10329655 |doi-access=free}}</ref> A human male weighing 68&nbsp;kg (150&nbsp;lb) normally synthesizes about 1 gram (1,000&nbsp;mg) of cholesterol per day, and his body contains about 35 g, mostly contained within the cell membranes.

Typical daily cholesterol dietary intake for a man in the United States is 307&nbsp;mg.<ref name="cdc-calories">{{cite web | title = National Health and Nutrition Examination Survey | publisher = United States Center for Disease Control | url = https://www.cdc.gov/nchs/data/nhanes/databriefs/calories.pdf | access-date = 2012-01-28}}
</ref> Most ingested cholesterol is [[esterified]], which causes it to be poorly absorbed by the gut. The body also compensates for absorption of ingested cholesterol by reducing its own cholesterol synthesis.<ref>
{{cite journal | vauthors = Lecerf JM, de Lorgeril M | title = Dietary cholesterol: from physiology to cardiovascular risk | journal = The British Journal of Nutrition | volume = 106 | issue = 1 | pages = 6–14 | date = July 2011 | pmid = 21385506 | doi = 10.1017/S0007114511000237 | doi-access = free }}</ref> For these reasons, cholesterol in food, seven to ten hours after ingestion, has little, if any effect on concentrations of cholesterol in the blood. Surprisingly, in rats, blood cholesterol is inversely correlated with cholesterol consumption. The more cholesterol a rat eats the lower the blood cholesterol.<ref>{{cite journal |last1=Angel |first1=A |last2=Farkas |first2=J |title=Regulation of cholesterol storage in adipose tissue. |journal=Journal of Lipid Research |date=September 1974 |volume=15 |issue=5 |pages=491–9 |doi=10.1016/S0022-2275(20)36769-9 |pmid=4415522|doi-access=free }}</ref> During the first seven hours after ingestion of cholesterol, as absorbed fats are being distributed around the body within extracellular water by the various [[lipoprotein]]s (which transport all fats in the water outside cells), the concentrations increase.<ref>{{cite journal | vauthors = Dubois C, Armand M, Mekki N, Portugal H, Pauli AM, Bernard PM, Lafont H, Lairon D | display-authors = 6 | title = Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects | journal = Journal of Lipid Research | volume = 35 | issue = 11 | pages = 1993–2007 | date = November 1994 | doi = 10.1016/S0022-2275(20)39946-6 | pmid = 7868978 | doi-access = free }}</ref>

Plants make cholesterol in very small amounts.<ref name="Plant cholesterol">{{cite journal | journal = Journal of Chemical Education | vauthors = Behrman EJ, Gopalan V | title=Cholesterol and Plants | veditors = Scovell WM | volume = 82 | number = 12 | year = 2005 | pages = 1791 | doi = 10.1021/ed082p1791|bibcode=2005JChEd..82.1791B }}</ref> In larger quantities they produce [[phytosterol]]s, chemically similar substances which can compete with cholesterol for reabsorption in the intestinal tract, thus potentially reducing cholesterol reabsorption.<ref name="John_2007">{{cite journal | vauthors = John S, Sorokin AV, Thompson PD | title = Phytosterols and vascular disease | journal = Current Opinion in Lipidology | volume = 18 | issue = 1 | pages = 35–40 | date = February 2007 | pmid = 17218830 | doi = 10.1097/MOL.0b013e328011e9e3 | s2cid = 29213889 }}</ref> When intestinal lining cells absorb phytosterols, in place of cholesterol, they usually excrete the phytosterol molecules back into the [[GI tract]], an important protective mechanism. The intake of naturally occurring phytosterols, which encompass plant [[sterols]] and [[Stanol ester|stanols]], ranges between ≈200–300&nbsp;mg/day depending on eating habits.<ref>{{cite journal | vauthors = Jesch ED, Carr TP | title = Food Ingredients That Inhibit Cholesterol Absorption | journal = Preventive Nutrition and Food Science | volume = 22 | issue = 2 | pages = 67–80 | date = June 2017 | pmid = 28702423 | pmc = 5503415 | doi = 10.3746/pnf.2017.22.2.67 }}</ref> Specially designed vegetarian experimental diets have been produced yielding upwards of 700&nbsp;mg/day.<ref>{{cite journal | vauthors = Agren JJ, Tvrzicka E, Nenonen MT, Helve T, Hänninen O | title = Divergent changes in serum sterols during a strict uncooked vegan diet in patients with rheumatoid arthritis | journal = The British Journal of Nutrition | volume = 85 | issue = 2 | pages = 137–139 | date = February 2001 | pmid = 11242480 | doi = 10.1079/BJN2000234 | doi-access = free }}</ref>

===Function===

====Membranes====
Cholesterol is present in varying degrees in all animal [[cell membrane]]s, but is absent in prokaryotes.<ref>''Biochemistry'',  7th ed., J. M. Berg, J. L. Tymoczko, & L. Stryer, 2010, p. 350. 
</ref> It is required to build and maintain membranes and modulates [[membrane fluidity]] over the range of physiological temperatures. The [[hydroxyl]] group of each cholesterol molecule interacts with water molecules surrounding the membrane, as do the [[Polar molecules|polar]] heads of the [[lipid bilayer|membrane]] [[phospholipid]]s and [[sphingolipid]]s, while the bulky [[steroid]] and the [[hydrocarbon]] chain are embedded in the membrane, alongside the [[Polar molecules#Nonpolar molecules|nonpolar]] [[Fatty acid|fatty-acid chain]] of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which both alters membrane fluidity<ref name="isbn1-4292-4646-4">{{cite book |vauthors=Sadava D, Hillis DM, Heller HC, Berenbaum MR | chapter = Cell Membranes | title = Life: The Science of Biology | edition = 9th | publisher = Freeman | location = San Francisco | year = 2011 | pages = 105–114 | isbn = 978-1-4292-4646-0 }}</ref> and maintains membrane integrity so that animal cells do not need to build cell walls (like plants and most bacteria). The membrane remains stable and durable without being rigid, allowing animal cells to change shape and animals to move.

The structure of the [[tetracyclic]] ring of cholesterol contributes to the fluidity of the cell membrane, as the molecule is in a ''trans'' conformation making all but the side chain of cholesterol rigid and planar.<ref name="Ohvo-Rekilä_2002">{{cite journal | vauthors = Ohvo-Rekilä H, Ramstedt B, Leppimäki P, Slotte JP | title = Cholesterol interactions with phospholipids in membranes | journal = Progress in Lipid Research | volume = 41 | issue = 1 | pages = 66–97 | date = January 2002 | pmid = 11694269 | doi = 10.1016/S0163-7827(01)00020-0 }}</ref> In this structural role, cholesterol also reduces the permeability of the plasma membrane to neutral solutes,<ref name="Yeagle_1991">{{cite journal | vauthors = Yeagle PL | title = Modulation of membrane function by cholesterol | journal = Biochimie | volume = 73 | issue = 10 | pages = 1303–1310 | date = October 1991 | pmid = 1664240 | doi = 10.1016/0300-9084(91)90093-G }}</ref> [[hydrogen]] ions, and [[sodium]] ions.<ref name="Haines_2001">{{cite journal | vauthors = Haines TH | title = Do sterols reduce proton and sodium leaks through lipid bilayers? | journal = Progress in Lipid Research | volume = 40 | issue = 4 | pages = 299–324 | date = July 2001 | pmid = 11412894 | doi = 10.1016/S0163-7827(01)00009-1 | s2cid = 32236169 }}</ref>

====Substrate presentation====
Cholesterol regulates the biological process of [[substrate presentation]] and the enzymes that use substrate presentation as a mechanism of their activation. Phospholipase D2 ([[PLD2]]) is a well-defined example of an enzyme activated by substrate presentation.<ref>{{cite journal | vauthors = Petersen EN, Chung HW, Nayebosadri A, Hansen SB | title = Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D | journal = Nature Communications | volume = 7 | pages = 13873 | date = December 2016 | pmid = 27976674 | pmc = 5171650 | doi = 10.1038/ncomms13873 | bibcode = 2016NatCo...713873P }}</ref> The enzyme is [[palmitoylation|palmitoylated]] causing the enzyme to traffic to cholesterol dependent lipid domains sometimes called "[[lipid rafts]]". The substrate of [[phospholipase D]] is [[phosphatidylcholine]] (PC) which is unsaturated and is of low abundance in lipid rafts. PC localizes to the disordered region of the cell along with the polyunsaturated lipid [[phosphatidylinositol 4,5-bisphosphate]] (PIP2). PLD2 has a PIP2 [[binding domain]]. When PIP2 concentration in the membrane increases, PLD2 leaves the cholesterol-dependent domains and binds to PIP2 where it then gains access to its substrate PC and commences catalysis based on substrate presentation.
[[File:Enzyme translocation.png|thumb|right|upright=2|'''[[Substrate presentation]]'''; PLD (blue oval) is sequestered into cholesterol-dependent lipid domains (green lipids) by [[palmitoylation]]. PLD also binds PIP2(red hexagon) domains (grey shading) located in the disordered region of the cell with phosphatidylcholine (PC). When cholesterol decreases or PIP2 increases in the cell, PLD translocates to PIP2 where it is exposed to and hydrolizes PC to phosphatidic acid (red spherical lipid).]]

====Signaling====
{{Main|Cholesterol signaling}}

Cholesterol is also implicated in cell signaling processes, assisting in the formation of [[lipid raft]]s in the [[plasma membrane]], which brings receptor proteins in close proximity with high concentrations of second messenger molecules.<ref name="Incardona_2000">{{cite journal | vauthors = Incardona JP, Eaton S | title = Cholesterol in signal transduction | journal = Current Opinion in Cell Biology | volume = 12 | issue = 2 | pages = 193–203 | date = April 2000 | pmid = 10712926 | doi = 10.1016/S0955-0674(99)00076-9 }}
</ref> In multiple layers, cholesterol and phospholipids, both electrical insulators, can facilitate speed of transmission of electrical impulses along nerve tissue. For many neuron fibers, a [[myelin]] sheath, rich in cholesterol since it is derived from compacted layers of [[Schwann cell]] or oligodendrocyte membranes, provides insulation for more efficient conduction of impulses.<ref name="isbn0-7817-5056-3">{{cite book |vauthors=Pawlina W, Ross MW | chapter = Supporting Cells of the Nervous System | title = Histology: a text and atlas: with correlated cell and molecular biology | edition = 5th | publisher = Lippincott Williams & Wilkins | location = Philadelphia | year = 2006 | pages = 339 | isbn = 978-0-7817-5056-1 }}</ref> [[Demyelination]] (loss of myelin) is believed to be part of the basis for [[multiple sclerosis]].

Cholesterol binds to and affects the gating of a number of [[ion channel]]s such as the [[nicotinic acetylcholine receptor]], [[GABAA receptor|GABA<sub>A</sub> receptor]], and the [[inward-rectifier potassium channel]].<ref name="LevitanSingh2014">{{cite journal | vauthors = Levitan I, Singh DK, Rosenhouse-Dantsker A | title = Cholesterol binding to ion channels | journal = Frontiers in Physiology | volume = 5 | pages = 65 | year = 2014 | pmid = 24616704 | pmc = 3935357 | doi = 10.3389/fphys.2014.00065 | doi-access = free }}</ref> Cholesterol also activates the [[estrogen-related receptor alpha]] (ERRα), and may be the [[Endogeny (biology)|endogenous]] [[ligand (biochemistry)|ligand]] for the [[receptor (biochemistry)|receptor]].<ref name="WeiSchwaid2016">{{cite journal | vauthors = Wei W, Schwaid AG, Wang X, Wang X, Chen S, Chu Q, Saghatelian A, Wan Y | display-authors = 6 | title = Ligand Activation of ERRα by Cholesterol Mediates Statin and Bisphosphonate Effects | journal = Cell Metabolism | volume = 23 | issue = 3 | pages = 479–491 | date = March 2016 | pmid = 26777690 | pmc = 4785078 | doi = 10.1016/j.cmet.2015.12.010 }}</ref><ref name="Elsevier2017">{{cite book | vauthors = Zuo H, Wan Y | chapter = Nuclear Receptors in Skeletal Homeostasis | veditors = Forrest D, Tsai S |title=Nuclear Receptors in Development and Disease| chapter-url = https://books.google.com/books?id=ZvupDQAAQBAJ&pg=PA88 |year=2017|publisher=Elsevier Science|isbn=978-0-12-802196-5|pages=88 }}</ref> The constitutively active nature of the receptor may be explained by the fact that cholesterol is ubiquitous in the body.<ref name="Elsevier2017" /> Inhibition of ERRα signaling by reduction of cholesterol production has been identified as a key mediator of the effects of [[statin]]s and [[bisphosphonate]]s on [[bone]], [[muscle]], and [[macrophage]]s.<ref name="WeiSchwaid2016" /><ref name="Elsevier2017" /> On the basis of these findings, it has been suggested that the ERRα should be de-orphanized and classified as a receptor for cholesterol.<ref name="WeiSchwaid2016" /><ref name="Elsevier2017" />

==== As a chemical precursor ====
Within cells, cholesterol is also a precursor molecule for several [[Metabolic pathway|biochemical pathway]]s. For example, it is the precursor molecule for the synthesis of [[vitamin D]] in the [[calcium metabolism]] and all [[steroid hormones]], including the [[adrenal gland]] hormones [[cortisol]] and [[aldosterone]], as well as the sex hormones [[progesterone]], [[estrogen]]s, and [[testosterone]], and their derivatives.<ref name="Hanukoglu_1992" /><ref name="Payne_2004">{{cite journal | vauthors = Payne AH, Hales DB | title = Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones | journal = Endocrine Reviews | volume = 25 | issue = 6 | pages = 947–70 | date = December 2004 | pmid = 15583024 | doi = 10.1210/er.2003-0030 | doi-access = free }}</ref>

====Epidermis====
The stratum corneum is the outermost layer of the epidermis.<ref name="Elias-2006">{{cite book | vauthors = Elias PM, Feingold KR | chapter = Stratum Corneum Barrier Function: Defintions and Broad Concepts | veditors = Elias PM |title=Skin barrier |date=2006 |publisher=Taylor & Francis |location=New York |isbn=978-0824758158}}</ref><ref name="Merleev et al-2022" /> It is composed of terminally differentiated and enucleated [[corneocyte]]s that reside within a lipid matrix, like "bricks and mortar."<ref name="Elias-2006" /><ref name="Merleev et al-2022">{{cite journal | vauthors = Merleev AA, Le ST, Alexanian C, Toussi A, Xie Y, Marusina AI, Watkins SM, Patel F, Billi AC, Wiedemann J, Izumiya Y, Kumar A, Uppala R, Kahlenberg JM, Liu FT, Adamopoulos IE, Wang EA, Ma C, Cheng MY, Xiong H, Kirane A, Luxardi G, Andersen B, Tsoi LC, Lebrilla CB, Gudjonsson JE, Maverakis E | display-authors = 6 | title = Biogeographic and disease-specific alterations in epidermal lipid composition and single-cell analysis of acral keratinocytes | journal = JCI Insight | volume = 7 | issue = 16 | date = August 2022 | pmid = 35900871 | pmc = 9462509 | doi = 10.1172/jci.insight.159762 }}</ref> Together with [[ceramide]]s and free fatty acids, cholesterol forms the lipid mortar, a water-impermeable barrier that prevents evaporative water loss. As a rule of thumb, the epidermal lipid matrix is composed of an equimolar mixture of ceramides (≈50% by weight), cholesterol (≈25% by weight), and free fatty acids (≈15% by weight), with smaller quantities of other lipids also being present.<ref name="Elias-2006" /><ref name="Merleev et al-2022" /> Cholesterol sulfate reaches its highest concentration in the granular layer of the epidermis. Steroid sulfate sulfatase then decreases its concentration in the stratum corneum, the outermost layer of the epidermis.<ref>{{cite journal | vauthors = Elias PM, Williams ML, Maloney ME, Bonifas JA, Brown BE, Grayson S, Epstein EH | title = Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis | journal = The Journal of Clinical Investigation | volume = 74 | issue = 4 | pages = 1414–1421 | date = October 1984 | pmid = 6592175 | pmc = 425309 | doi = 10.1172/JCI111552 }}</ref> The relative abundance of cholesterol sulfate in the epidermis varies across different body sites with the heel of the foot having the lowest concentration.<ref name="Merleev et al-2022" />

=== Metabolism ===
Cholesterol is [[Enterohepatic circulation|recycled]] in the body. The liver excretes cholesterol into [[bile|biliary]] fluids, which are then stored in the [[gallbladder]], which then excretes them in a non-[[ester]]ified form (via bile) into the digestive tract. Typically, about 50% of the excreted cholesterol is reabsorbed by the [[small intestine]] back into the bloodstream.

==Biosynthesis and regulation==
===Biosynthesis===
Almost all animal tissues synthesize cholesterol from [[acetyl-CoA]]. All animal cells (exceptions exist within the invertebrates) manufacture cholesterol, for both membrane structure and other uses, with relative production rates varying by cell type and organ function. About 80% of total daily cholesterol production occurs in the [[liver]] and the [[intestines]];<ref>{{Cite news|url=https://www.health.harvard.edu/heart-health/how-its-made-cholesterol-production-in-your-body|title=How it's made: Cholesterol production in your body | publisher = Harvard Health Publishing |access-date=2018-10-18|language=en-US}}</ref> other sites of higher [[biosynthesis|synthesis]] rates include the [[brain]], the [[adrenal gland]]s, and the [[reproductive organ]]s.

Synthesis within the body starts with the [[mevalonate pathway]] where two molecules of [[acetyl CoA]] condense to form [[acetoacetyl-CoA]]. This is followed by a second condensation between [[acetyl CoA]] and [[acetoacetyl-CoA]] to form [[3-hydroxy-3-methylglutaryl CoA]] ([[HMG-CoA]]).<ref name="Mehta">{{cite web|url=http://pharmaxchange.info/press/2013/09/biosynthesis-and-regulation-of-cholesterol-animation/|title=Biosynthesis and Regulation of Cholesterol (with Animation)|website=PharmaXChange.info|date=17 September 2013}}</ref>
[[File:Condensation of Acetyl-CoA to HMG-CoA.gif|center|frameless|500px]]

This molecule is then reduced to [[mevalonate]] by the enzyme [[HMG-CoA reductase]]. Production of [[mevalonate]] is the rate-limiting and irreversible step in cholesterol synthesis and is the site of action for [[statin]]s (a class of cholesterol-lowering drugs).

[[File:Melavonic Acid Synthesis.gif|center|frameless|500px]]
Mevalonate is finally converted to [[isopentenyl pyrophosphate]] (IPP) through two phosphorylation steps and one decarboxylation step that requires [[Adenosine triphosphate|ATP]].

[[File:Melavonate pathway to IPP.gif|center|frameless|500px]]

Three molecules of isopentenyl pyrophosphate condense to form [[farnesyl pyrophosphate]] through the action of geranyl transferase.

[[File:Cation formation from DMAPP.gif|center|frameless|500px]]
[[File:Farnesylpyrophosphate synthase (FPPS) reaction.svg|center|frameless|500px]]

Two molecules of farnesyl pyrophosphate then condense to form [[squalene]] by the action of [[squalene synthase]] in the [[endoplasmic reticulum]].<ref name="Mehta" />
[[File:Squalene Synthesis.gif|center|frameless|500px]]
[[File:Squalene Synthesis 2.gif|center|frameless|500px]]

[[Oxidosqualene cyclase]] then cyclizes squalene to form [[lanosterol]].

[[File:Flavinoid Mechanism.gif|center|frameless|500px]]
[[File:Oxidosqualene.gif|center|frameless|500px]]
[[File:Lanosterol formation.gif|center|frameless|500px]]

Finally, [[lanosterol]] is converted to cholesterol via either of two pathways, the Bloch pathway, or the Kandutsch-Russell pathway.<ref>{{cite web |title=Cholesterol metabolism (includes both Bloch and Kandutsch-Russell pathways) (Mus musculus) – WikiPathways |url=https://www.wikipathways.org/index.php/Pathway:WP4346 |website=www.wikipathways.org |access-date=2 February 2021}}</ref><ref>{{cite journal | vauthors = Singh P, Saxena R, Srinivas G, Pande G, Chattopadhyay A | title = Cholesterol biosynthesis and homeostasis in regulation of the cell cycle | journal = PLOS ONE | volume = 8 | issue = 3 | pages = e58833 | date = 2013 | pmid = 23554937 | pmc = 3598952 | doi = 10.1371/journal.pone.0058833 | doi-access = free | bibcode = 2013PLoSO...858833S }}</ref><ref>{{cite web |title=Kandutsch-Russell pathway |url=https://pubchem.ncbi.nlm.nih.gov/pathway/Reactome:R-HSA-6807062 |website=pubchem.ncbi.nlm.nih.gov |access-date=2 February 2021 |language=en}}</ref><ref>{{cite book | vauthors = Berg J | title = Biochemistry | year = 2002 | publisher = WH Freeman | location = New York | isbn = 978-0-7167-3051-4 | url-access = registration | url = https://archive.org/details/biochemistrychap00jere }}</ref><ref name="isbn0-7167-2009-4">{{cite book |vauthors=Rhodes CM, Stryer L, Tasker R | title = Biochemistry | edition = 4th | publisher = W.H. Freeman | location = San Francisco | year = 1995 | pages = 280, 703 | isbn = 978-0-7167-2009-6 }}</ref>
The final 19 steps to cholesterol contain [[NADPH]] and oxygen to help oxidize [[methyl group]]s for removal of carbons, [[mutase]]s to move [[alkene]] groups, and [[NADH]] to help reduce [[ketones]].
[[File:Cholesterol Synthesis 19 step.gif|center|frameless|700px]]
[[File:Cholesterol Synthesis 12.gif|center|frameless|700px]]

[[Konrad Bloch]] and [[Feodor Lynen]] shared the [[Nobel Prize in Physiology or Medicine]] in 1964 for their discoveries concerning some of the mechanisms and methods of regulation of cholesterol and [[fatty acid metabolism]].<ref>{{Cite web|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/1964/|title=The Nobel Prize in Physiology or Medicine, 1964|publisher=Nobel Prize, Nobel Media }}</ref>

===Regulation of cholesterol synthesis===
Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the [[homeostasis|homeostatic]] mechanisms involved are only partly understood. A higher intake of food leads to a net decrease in endogenous production, whereas a lower intake of 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="Espenshade_2007">{{cite journal | vauthors = Espenshade PJ, Hughes AL | title = Regulation of sterol synthesis in eukaryotes | journal = Annual Review of Genetics | volume = 41 | pages = 401–427 | year = 2007 | pmid = 17666007 | doi = 10.1146/annurev.genet.41.110306.130315 }}</ref> In the presence of cholesterol, SREBP is bound to two other proteins: [[SREBP cleavage-activating protein|SCAP]] (SREBP cleavage-activating protein) and [[INSIG-1]]. When cholesterol levels fall, INSIG-1 dissociates from the SREBP-SCAP complex, which allows the complex to migrate to the [[Golgi apparatus]]. Here SREBP is cleaved by S1P and S2P (site-1 protease and site-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), which stimulates the [[Transcription (genetics)|transcription]] of many genes. Among these are the low-density lipoprotein ([[Low-density lipoprotein|LDL]]) receptor and [[HMG-CoA reductase]]. The LDL receptor scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase in endogenous production of cholesterol.<ref>{{cite journal | vauthors = Brown MS, Goldstein JL | title = The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor | journal = Cell | volume = 89 | issue = 3 | pages = 331–340 | date = May 1997 | pmid = 9150132 | doi = 10.1016/S0092-8674(00)80213-5 | s2cid = 17882616 | doi-access = free }}</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 the expression of many genes that control lipid formation and metabolism and body fuel allocation.

Cholesterol synthesis can also be turned off when cholesterol levels are high. HMG-CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and a membrane domain. The membrane domain senses signals for its degradation. Increasing concentrations of cholesterol (and other sterols) cause a change in this domain's oligomerization state, which makes it more susceptible to destruction by the [[proteasome]]. This enzyme's activity can also be reduced by phosphorylation by an AMP-activated protein [[kinase]]. Because this kinase is activated by AMP, which is produced when ATP is hydrolyzed, it follows that cholesterol synthesis is halted when ATP levels are low.<ref name="isbn0-7167-4955-6">{{cite book | vauthors = Tymoczko JL, Berg T, Stryer L, Berg JM | title = Biochemistry | publisher = W.H. Freeman | location = San Francisco | year = 2002 | pages = [https://archive.org/details/biochemistry200100jere/page/726 726–727] | isbn = 978-0-7167-4955-4 | url =https://archive.org/details/biochemistry200100jere| url-access = registration }}</ref>

===Plasma transport and regulation of absorption===
{{See also|Blood lipids}}

[[File:MetabolismoLipidiE.png|thumb|Lipid logistics: transport of triglycerides and cholesterol in organisms in form of lipoproteins as chylomicrons, VLDL, LDL, IDL, HDL.]]
As an isolated molecule, cholesterol is only minimally soluble in [[water]], or [[hydrophilic]]. Because of this, it dissolves in blood at exceedingly small concentrations. To be transported effectively, cholesterol is instead packaged within [[lipoprotein]]s, complex [[Disk (mathematics)|discoidal]] particles with exterior [[amphiphile|amphiphilic]] proteins and lipids, whose outward-facing surfaces are water-soluble and inward-facing surfaces are lipid-soluble. This allows it to travel through the blood via [[emulsification]]. Unbound cholesterol, being amphipathic, is transported in the monolayer surface of the lipoprotein particle along with phospholipids and proteins. Cholesterol esters bound to fatty acid, on the other hand, are transported within the fatty hydrophobic core of the lipoprotein, along with triglyceride.<ref name="Patton 2010">{{cite book | vauthors = Patton KT, Thibodeau GA |title=Anatomy and Physiology |date=2010 |publisher=Mosby/Elsevier |isbn=978-9996057762 |edition=7th }}{{page needed|date=July 2023}}</ref>

There are several types of lipoproteins in the blood. In order of increasing density, they are [[chylomicron]]s, [[very-low-density lipoprotein]] (VLDL), [[intermediate-density lipoprotein]] (IDL), [[low-density lipoprotein]] (LDL), and [[high-density lipoprotein]] (HDL). Lower protein/lipid ratios make for less dense lipoproteins. Cholesterol within different lipoproteins is identical, although some is carried as its native "free" alcohol form (the cholesterol-OH group facing the water surrounding the particles), while others as fatty acyl esters, known also as cholesterol esters, within the particles.<ref name="Patton 2010"/>

Lipoprotein particles are organized by complex [[apolipoproteins]], typically 80–100 different proteins per particle, which can be recognized and bound by specific receptors on cell membranes, directing their lipid payload into specific cells and tissues currently ingesting these fat transport particles. These surface receptors serve as unique molecular signatures, which then help determine fat distribution delivery throughout the body.<ref name="Patton 2010"/>

Chylomicrons, the least dense cholesterol transport particles, contain [[apolipoprotein B-48]], [[apolipoprotein C]], and [[apolipoprotein E]] (the principal cholesterol carrier in the brain<ref>{{cite journal | vauthors = Mahley RW | title = Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders | journal = Journal of Molecular Medicine | volume = 94 | issue = 7 | pages = 739–746 | date = July 2016 | pmid = 27277824 | pmc = 4921111 | doi = 10.1007/s00109-016-1427-y }}</ref>) in their shells. Chylomicrons carry fats from the intestine to muscle and other tissues in need of fatty acids for energy or fat production. Unused cholesterol remains in more cholesterol-rich chylomicron remnants, and taken up from here to the bloodstream by the liver.<ref name="Patton 2010"/>

VLDL particles are produced by the liver from [[Triglyceride|triacylglycerol]] and cholesterol which was not used in the synthesis of bile acids. These particles contain [[apolipoprotein B100]] and [[apolipoprotein E]] in their shells, and can be degraded by [[lipoprotein lipase]] on the artery wall to IDL. This arterial wall cleavage allows absorption of [[Triglyceride|triacylglycerol]] and increases the concentration of circulating cholesterol. IDL particles are then consumed in two processes: half is metabolized by [[HTGL]] and taken up by the LDL receptor on the liver cell surfaces, while the other half continues to lose triacylglycerols in the bloodstream until they become cholesterol-laden LDL particles.<ref name="Patton 2010"/>

LDL particles are the major blood cholesterol carriers. Each one contains approximately 1,500 molecules of cholesterol ester. LDL particle shells contain just one molecule of [[apolipoprotein B100]], recognized by [[LDL receptor]]s in peripheral tissues. Upon binding of [[apolipoprotein B100]], many LDL receptors concentrate in [[clathrin]]-coated pits. Both LDL and its receptor form vesicles within a cell via [[endocytosis]]. These vesicles then fuse with a [[lysosome]], where the [[Lysosomal lipase|lysosomal acid lipase]] enzyme hydrolyzes the cholesterol esters. The cholesterol can then be used for membrane biosynthesis or esterified and stored within the cell, so as to not interfere with the cell membranes.<ref name="Patton 2010"/>

LDL receptors are used up during cholesterol absorption, and its synthesis is regulated by [[SREBP]], the same protein that controls the synthesis of cholesterol ''de novo'', according to its presence inside the cell. A cell with abundant cholesterol will have its LDL receptor synthesis blocked, to prevent new cholesterol in LDL particles from being taken up. Conversely, LDL receptor synthesis proceeds when a cell is deficient in cholesterol.<ref name="Patton 2010"/>

When this process becomes unregulated, LDL particles without receptors begin to appear in the blood. These LDL particles are oxidized and taken up by [[macrophages]], which become engorged and form foam cells. These foam cells often become trapped in the walls of blood vessels and contribute to [[atheroma|atherosclerotic plaque]] formation. Differences in cholesterol homeostasis affect the development of early atherosclerosis (carotid intima-media thickness).<ref name="Weingärtner_2010">{{cite journal | vauthors = Weingärtner O, Pinsdorf T, Rogacev KS, Blömer L, Grenner Y, Gräber S, Ulrich C, Girndt M, Böhm M, Fliser D, Laufs U, Lütjohann D, Heine GH | display-authors = 6 | title = The relationships of markers of cholesterol homeostasis with carotid intima-media thickness | journal = PLOS ONE| volume = 5 | issue = 10 | pages = e13467 | date = October 2010 | pmid = 20976107 | pmc = 2956704 | doi = 10.1371/journal.pone.0013467 | veditors = Federici M | bibcode = 2010PLoSO...513467W | doi-access = free }}</ref> 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 [[lipoprotein]]) with "bad" cholesterol.<ref name="isbn0-7167-4955-6"/>

HDL particles are thought to transport cholesterol back to the liver, either for excretion or for other tissues that synthesize hormones, in a process known as [[reverse cholesterol transport]] (RCT).<ref name="Lewis_2005">{{cite journal | vauthors = Lewis GF, Rader DJ | title = New insights into the regulation of HDL metabolism and reverse cholesterol transport | journal = Circulation Research | volume = 96 | issue = 12 | pages = 1221–1232 | date = June 2005 | pmid = 15976321 | doi = 10.1161/01.RES.0000170946.56981.5c | doi-access =  }}</ref> Large numbers of HDL particles correlates with better health outcomes,<ref name="Gordon_1989">{{cite journal | vauthors = Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, Jacobs DR, Bangdiwala S, Tyroler HA | display-authors = 6 | title = High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies | journal = Circulation | volume = 79 | issue = 1 | pages = 8–15 | date = January 1989 | pmid = 2642759 | doi = 10.1161/01.CIR.79.1.8 | doi-access = free }}</ref> whereas low numbers of HDL particles is associated with [[atheroma]]tous disease progression in the arteries.<ref>{{cite journal | vauthors = Miller NE, Thelle DS, Forde OH, Mjos OD | title = The Tromsø heart-study. High-density lipoprotein and coronary heart-disease: a prospective case-control study | journal = Lancet | volume = 1 | issue = 8019 | pages = 965–968 | date = May 1977 | pmid = 67464 | doi = 10.1016/s0140-6736(77)92274-7 | s2cid = 140204202 }}</ref>

===Metabolism, recycling and excretion===
Cholesterol is susceptible to oxidation and easily forms oxygenated derivatives called [[oxysterol]]s. Three different mechanisms can form these: autoxidation, secondary oxidation to lipid peroxidation, and cholesterol-metabolizing enzyme oxidation. A great interest in oxysterols arose when they were shown to exert inhibitory actions on cholesterol biosynthesis.<ref name="Kandutsch_1978">{{cite journal | vauthors = Kandutsch AA, Chen HW, Heiniger HJ | title = Biological activity of some oxygenated sterols | journal = Science | volume = 201 | issue = 4355 | pages = 498–501 | date = August 1978 | pmid = 663671 | doi = 10.1126/science.663671 | bibcode = 1978Sci...201..498K }}</ref> This finding became known as the "oxysterol hypothesis". Additional roles for oxysterols in human physiology include their participation in bile acid biosynthesis, function as transport forms of cholesterol, and regulation of gene transcription.<ref name="Russell_2000">{{cite journal | vauthors = Russell DW | title = Oxysterol biosynthetic enzymes | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1529 | issue = 1–3 | pages = 126–35 | date = December 2000 | pmid = 11111082 | doi = 10.1016/S1388-1981(00)00142-6 }}</ref>

In biochemical experiments radiolabelled forms of cholesterol, such as tritiated-cholesterol are used. These derivatives undergo degradation upon storage and it is essential to purify cholesterol prior to use. Cholesterol can be purified using small Sephadex LH-20 columns.<ref name="Hanukoglu_1980">{{cite journal | vauthors = Hanukoglu I, Jefcoate CR | title = Pregnenolone separation from cholesterol using Sephadex LH-20 mini-columns|journal=Journal of Chromatography A | volume = 190 | issue = 1 | year = 1980 | pages = 256–262 | doi = 10.1016/S0021-9673(00)85545-4 | url = https://zenodo.org/record/890904 }}</ref>

Cholesterol is oxidized by the liver into a variety of [[bile acids]].<ref name="Javitt_1994">{{cite journal | vauthors = Javitt NB | title = Bile acid synthesis from cholesterol: regulatory and auxiliary pathways | journal = FASEB Journal | volume = 8 | issue = 15 | pages = 1308–1311 | date = December 1994 | pmid = 8001744 | doi = 10.1096/fasebj.8.15.8001744 | doi-access = free | s2cid = 20302590 }}</ref> These, in turn, are [[phase 2 reaction|conjugated]] with [[glycine]], [[taurine]], [[glucuronic acid]], or [[sulfate]]. A mixture of conjugated and nonconjugated 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 are lost in the feces.<ref name="Wolkoff_2003">{{cite journal | vauthors = Wolkoff AW, Cohen DE | title = Bile acid regulation of hepatic physiology: I. Hepatocyte transport of bile acids | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 284 | issue = 2 | pages = G175–G179 | date = February 2003 | pmid = 12529265 | doi = 10.1152/ajpgi.00409.2002 }}</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 ([[lecithin]] and [[bilirubin]] gallstones also occur, but less frequently).<ref name="Marschall_2007">{{cite journal | vauthors = Marschall HU, Einarsson C | title = Gallstone disease | journal = Journal of Internal Medicine | volume = 261 | issue = 6 | pages = 529–542 | date = June 2007 | pmid = 17547709 | doi = 10.1111/j.1365-2796.2007.01783.x | s2cid = 8609639 | doi-access = free }}</ref> Every day, up to 1 g of cholesterol enters the colon. This cholesterol originates from the diet, bile, and desquamated intestinal cells, and can be metabolized by the colonic bacteria. Cholesterol is converted mainly into [[coprostanol]], a nonabsorbable sterol that is excreted in the feces.{{citation needed|date=March 2019}}

Although cholesterol is a steroid generally associated with mammals, the human pathogen ''[[Mycobacterium tuberculosis]]'' is able to completely degrade this molecule and contains a large number of genes that are regulated by its presence.<ref>{{cite journal | vauthors = Wipperman MF, Sampson NS, Thomas ST | title = Pathogen roid rage: cholesterol utilization by Mycobacterium tuberculosis | journal = Critical Reviews in Biochemistry and Molecular Biology | volume = 49 | issue = 4 | pages = 269–293 | date = 2014 | pmid = 24611808 | pmc = 4255906 | doi = 10.3109/10409238.2014.895700 }}</ref> Many of these cholesterol-regulated genes are [[Homology (biology)|homologues]] of [[fatty acid]] [[β-oxidation]] genes, but have evolved in such a way as to bind large steroid substrates like cholesterol.<ref>{{cite journal | vauthors = Thomas ST, Sampson NS | title = Mycobacterium tuberculosis utilizes a unique heterotetrameric structure for dehydrogenation of the cholesterol side chain | journal = Biochemistry | volume = 52 | issue = 17 | pages = 2895–2904 | date = April 2013 | pmid = 23560677 | pmc = 3726044 | doi = 10.1021/bi4002979 }}</ref><ref>{{cite journal | vauthors = Wipperman MF, Yang M, Thomas ST, Sampson NS | title = Shrinking the FadE proteome of Mycobacterium tuberculosis: insights into cholesterol metabolism through identification of an α2β2 heterotetrameric acyl coenzyme A dehydrogenase family | journal = Journal of Bacteriology | volume = 195 | issue = 19 | pages = 4331–4341 | date = October 2013 | pmid = 23836861 | pmc = 3807453 | doi = 10.1128/JB.00502-13 }}</ref>

==Dietary sources==
[[Animal fat]]s are complex mixtures of [[triglyceride]]s, with lesser amounts of both the [[phospholipid]]s and cholesterol molecules from which all animal (and human) cell membranes are constructed. Since all animal cells manufacture cholesterol, all animal-based foods contain cholesterol in varying amounts.<ref name="isbn0-9531949-5-7">{{cite book|title=Lipid analysis: isolation, separation, identification, and structural analysis of lipids| vauthors = Christie WW |publisher=Oily Press|year=2003|isbn=978-0-9531949-5-7|location=Ayr, Scotland }} {{page needed|date=July 2023}}</ref> Major dietary sources of cholesterol include [[red meat]], [[Yolk|egg yolks]] and whole [[Egg as food|egg]]s, [[liver]], [[kidney]], [[giblets]], [[fish oil]], and [[butter]].<ref name="USDA">{{cite web|url=https://ndb.nal.usda.gov/ndb/nutrients/report?nutrient1=601&nutrient2=&nutrient3=&&max=25&subset=0&offset=0&sort=c&totCount=7211&measureby=g|title=Cholesterol content in foods, rank order per 100 g; In: USDA Food Composition Databases|publisher=United States Department of Agriculture|date=2019|access-date=4 March 2019}}{{dead link|date=October 2022|bot=medic}}{{cbignore|bot=medic}}</ref> Human [[breast milk]] also contains significant quantities of cholesterol.<ref name="ajcn-breastmilk">{{cite journal | vauthors = Jensen RG, Hagerty MM, McMahon KE | title = Lipids of human milk and infant formulas: a review | journal = The American Journal of Clinical Nutrition | volume = 31 | issue = 6 | pages = 990–1016 | date = June 1978 | pmid = 352132 | doi = 10.1093/ajcn/31.6.990 | doi-access = free }}</ref>

Plant cells synthesize cholesterol as a precursor for other compounds, such as [[phytosterols]] and [[steroid]]al [[glycoalkaloid]]s, with cholesterol remaining in plant foods only in minor amounts or absent.<ref name="USDA" /><ref name="sonawane">{{cite journal | vauthors = Sonawane PD, Pollier J, Panda S, Szymanski J, Massalha H, Yona M, Unger T, Malitsky S, Arendt P, Pauwels L, Almekias-Siegl E, Rogachev I, Meir S, Cárdenas PD, Masri A, Petrikov M, Schaller H, Schaffer AA, Kamble A, Giri AP, Goossens A, Aharoni A | display-authors = 6 | title = Plant cholesterol biosynthetic pathway overlaps with phytosterol metabolism | journal = Nature Plants | volume = 3 | issue = 1 | pages = 16205 | date = December 2016 | pmid = 28005066 | doi = 10.1038/nplants.2016.205 | s2cid = 5518449 }}</ref> Some plant foods, such as [[avocado]], [[flax seed]]s and [[peanut]]s, contain phytosterols, which compete with cholesterol for absorption in the intestines, and reduce the absorption of both dietary and bile cholesterol.<ref>{{cite journal | vauthors = De Smet E, Mensink RP, Plat J | title = Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present | journal = Molecular Nutrition & Food Research | volume = 56 | issue = 7 | pages = 1058–1072 | date = July 2012 | pmid = 22623436 | doi = 10.1002/mnfr.201100722 | doi-access =  }}</ref> A typical diet contributes on the order of 0.2 gram of phytosterols, which is not enough to have a significant impact on blocking cholesterol absorption. Phytosterols intake can be supplemented through the use of phytosterol-containing [[functional foods]] or [[dietary supplement]]s that are recognized as having potential to reduce levels of [[low-density lipoprotein|LDL]]-cholesterol.<ref>{{cite web|url=http://www.efsa.europa.eu/en/efsajournal/pub/1813|title=Scientific opinion on the substantiation of health claims related to plant sterols and plant stanols and maintenance of normal blood cholesterol concentrations|year=2010|author=European Food Safety Authority, Journal}}</ref>

===Medical guidelines and recommendations===
In 2015, the scientific advisory panel of [[United States Department of Health and Human Services|U.S. Department of Health and Human Services]] and [[United States Department of Agriculture|U.S. Department of Agriculture]] for the 2015 iteration of the Dietary Guidelines for Americans dropped the previously recommended limit of consumption of dietary cholesterol to 300&nbsp;mg per day with a new recommendation to "eat as little dietary cholesterol as possible" and acknowledging an association between a diet low in cholesterol and reduced risk of cardiovascular disease.<ref>{{Cite web |title=2015-2020 Dietary Guidelines {{!}} health.gov |url=https://health.gov/our-work/nutrition-physical-activity/dietary-guidelines/previous-dietary-guidelines/2015 |access-date=2023-08-23 |website=health.gov}}</ref>

A 2013 report by the American Heart Association and the American College of Cardiology recommended focusing on healthy dietary patterns rather than specific cholesterol limits, as they are hard for clinicians and consumers to implement. They recommend the [[DASH diet|DASH]] and [[Mediterranean diet]], which are low in cholesterol.<ref>{{cite journal | vauthors = Carson JA, Lichtenstein AH, Anderson CA, Appel LJ, Kris-Etherton PM, Meyer KA, Petersen K, Polonsky T, Van Horn L | display-authors = 6 | title = Dietary Cholesterol and Cardiovascular Risk: A Science Advisory From the American Heart Association | journal = Circulation | volume = 141 | issue = 3 | pages = e39–e53 | date = January 2020 | pmid = 31838890 | doi = 10.1161/CIR.0000000000000743 | doi-access = free }}</ref> A 2017 review by the [[American Heart Association]] recommends switching [[saturated fats]] for [[polyunsaturated fats]] to reduce [[cardiovascular disease]] risk.<ref>{{cite journal | vauthors = Sacks FM, Lichtenstein AH, Wu JH, Appel LJ, Creager MA, Kris-Etherton PM, Miller M, Rimm EB, Rudel LL, Robinson JG, Stone NJ, Van Horn LV | display-authors = 6 | title = Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association | journal = Circulation | volume = 136 | issue = 3 | pages = e1–e23 | date = July 2017 | pmid = 28620111 | doi = 10.1161/CIR.0000000000000510 | s2cid = 367602 | doi-access = free }}</ref>

Some supplemental guidelines have recommended doses of phytosterols in the 1.6–3.0&nbsp;grams per day range (Health Canada, EFSA, ATP III, FDA). A meta-analysis demonstrated a 12% reduction in LDL-cholesterol at a mean dose of 2.1&nbsp;grams per day.<ref>{{cite journal | vauthors = Ras RT, Geleijnse JM, Trautwein EA | title = LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies | journal = The British Journal of Nutrition | volume = 112 | issue = 2 | pages = 214–219 | date = July 2014 | pmid = 24780090 | pmc = 4071994 | doi = 10.1017/S0007114514000750 }}</ref> The benefits of a diet supplemented with phytosterols have also been questioned.<ref name="Weingärtner_2009">{{cite journal | vauthors = Weingärtner O, Böhm M, Laufs U | title = Controversial role of plant sterol esters in the management of hypercholesterolaemia | journal = European Heart Journal | volume = 30 | issue = 4 | pages = 404–409 | date = February 2009 | pmid = 19158117 | pmc = 2642922 | doi = 10.1093/eurheartj/ehn580 }}</ref>

==Clinical significance==

===Hypercholesterolemia===
{{Main|Hypercholesterolemia|Lipid hypothesis}}
[[File:ColesterolemiaMortalitaE.png|thumb|Cholesterolemia and mortality for men and women <50 years and >60 years]]
According to the [[lipid hypothesis]], elevated levels of cholesterol in the blood lead to [[atherosclerosis]] which may increase the risk of [[myocardial infarction|heart attack]], [[stroke]], and [[peripheral artery disease]]. Since higher blood LDL – especially higher LDL concentrations and smaller LDL particle size – contributes to this process more than the cholesterol content of the HDL particles,<ref name="Brunzell_2008">{{cite journal | vauthors = Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, Witztum JL | title = Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation | journal = Diabetes Care | volume = 31 | issue = 4 | pages = 811–822 | date = April 2008 | pmid = 18375431 | doi = 10.2337/dc08-9018 | doi-access = free }}</ref> LDL particles are often termed "bad cholesterol". High concentrations of functional HDL, which can remove cholesterol from cells and atheromas, offer protection and are commonly referred to as "good cholesterol". These balances are mostly genetically determined, but can be changed by body composition, [[medication]]s, diet,<ref>{{cite web | url = https://www.heartuk.org.uk/healthy-diets/healthy-diets | archive-url = https://web.archive.org/web/20201029150758/https://www.heartuk.org.uk/healthy-diets/healthy-diets | archive-date = 29 October 2020 | work = Department of Health (UK), NHS Choices | title = More evidence for Mediterranean diet | date = 8 March 2011 | access-date = 11 November 2015 }}</ref> and other factors.<ref name="Durrington_2007">{{cite journal | vauthors = Durrington P | title = Dyslipidaemia | journal = Lancet | volume = 362 | issue = 9385 | pages = 717–731 | date = August 2003 | pmid = 12957096 | doi = 10.1016/S0140-6736(03)14234-1 | s2cid = 208792416 }}</ref> A 2007 study demonstrated that blood total cholesterol levels have an exponential effect on cardiovascular and total mortality, with the association more pronounced in younger subjects. Because cardiovascular disease is relatively rare in the younger population, the impact of high cholesterol on health is larger in older people.<ref name="Lewington_2007">{{cite journal | vauthors = Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, Halsey J, Qizilbash N, Peto R, Collins R | display-authors = 6 | title = Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths | journal = Lancet | volume = 370 | issue = 9602 | pages = 1829–1839 | date = December 2007 | pmid = 18061058 | doi = 10.1016/S0140-6736(07)61778-4 | s2cid = 54293528 }}</ref>

Elevated levels of the lipoprotein fractions, LDL, IDL and VLDL, rather than the total cholesterol level, correlate with the extent and progress of atherosclerosis.<ref name=NCEPIII>{{cite web | title = Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report | publisher = National Institutes of Health. National Heart, Lung and Blood Institute | url = https://www.nhlbi.nih.gov/files/docs/resources/heart/atp-3-cholesterol-full-report.pdf|date=1 September 2002 | access-date = 2008-10-27}}</ref> Conversely, the total cholesterol can be within normal limits, yet be made up primarily of small LDL and small HDL particles, under which conditions atheroma growth rates are high. A ''post hoc'' analysis of the IDEAL and the EPIC prospective studies found an association between high levels of HDL cholesterol (adjusted for apolipoprotein A-I and apolipoprotein B) and increased risk of cardiovascular disease, casting doubt on the cardioprotective role of "good cholesterol".<ref name="van_der_Steeg_2008">{{cite journal | vauthors = van der Steeg WA, Holme I, Boekholdt SM, Larsen ML, Lindahl C, Stroes ES, Tikkanen MJ, Wareham NJ, Faergeman O, Olsson AG, Pedersen TR, Khaw KT, Kastelein JJ | display-authors = 6 | title = High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies | journal = Journal of the American College of Cardiology | volume = 51 | issue = 6 | pages = 634–642 | date = February 2008 | pmid = 18261682 | doi = 10.1016/j.jacc.2007.09.060 | doi-access =  }}</ref><ref name="Robinson_2012">{{cite journal | vauthors = Robinson JG, Wang S, Jacobson TA | title = Meta-analysis of comparison of effectiveness of lowering apolipoprotein B versus low-density lipoprotein cholesterol and nonhigh-density lipoprotein cholesterol for cardiovascular risk reduction in randomized trials | journal = The American Journal of Cardiology | volume = 110 | issue = 10 | pages = 1468–1476 | date = November 2012 | pmid = 22906895 | doi = 10.1016/j.amjcard.2012.07.007 }}</ref>

About one in 250 individuals can have a genetic mutation for the LDL cholesterol receptor that causes them to have familial hypercholesterolemia.<ref name="pmid28864697">{{cite journal | vauthors = Akioyamen LE, Genest J, Shan SD, Reel RL, Albaum JM, Chu A, Tu JV | title = Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis | journal = BMJ Open | volume = 7 | issue = 9 | page = e016461 | date = September 2017 | pmid = 28864697 | pmc = 5588988 | doi = 10.1136/bmjopen-2017-016461 }}</ref> Inherited high cholesterol can also include genetic mutations in the PCSK9 gene and the gene for apolipoprotein B.<ref>{{Cite web|url=https://www.heart.org/en/health-topics/cholesterol/causes-of-high-cholesterol/familial-hypercholesterolemia-fh|title=Familial Hypercholesterolemia (FH)|website=www.heart.org|language=en|access-date=2019-08-02}}</ref>

Elevated cholesterol levels are treatable by a diet that reduces or eliminates saturated fat, trans fats, and high cholesterol foods,<ref name="aha-prev">{{cite web |url=https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia |title=Prevention and Treatment of High Cholesterol (Hyperlipidemia) |publisher=American Heart Association |access-date=23 August 2023 |date=2023}}</ref><ref name="mayo food" /> often followed by one of various [[Lipid-lowering agent|hypolipidemic agents]], such as [[statin]]s, [[fibrate]]s, cholesterol absorption inhibitors, [[monoclonal antibody therapy]] ([[PCSK9]] inhibitors), nicotinic acid derivatives or bile acid sequestrants.<ref name=NICE67>{{NICE|67|Lipid modification|2008}}</ref> There are several international guidelines on the treatment of hypercholesterolemia.<ref name="Mannu_2012">{{cite journal | vauthors = Mannu GS, Zaman MJ, Gupta A, Rehman HU, Myint PK | title = Update on guidelines for management of hypercholesterolemia | journal = Expert Review of Cardiovascular Therapy | volume = 10 | issue = 10 | pages = 1239–1249 | date = October 2012 | pmid = 23190064 | doi = 10.1586/erc.12.94 | s2cid = 5451203}}</ref>

Human trials using [[HMG-CoA reductase]] inhibitors, known as [[statin]]s, have repeatedly confirmed that changing lipoprotein transport patterns from unhealthy to healthier patterns significantly lowers cardiovascular disease event rates, even for people with cholesterol values currently considered low for adults.<ref>{{cite journal | vauthors = Kizer JR, Madias C, Wilner B, Vaughan CJ, Mushlin AI, Trushin P, Gotto AM, Pasternak RC | display-authors = 6 | title = Relation of different measures of low-density lipoprotein cholesterol to risk of coronary artery disease and death in a meta-regression analysis of large-scale trials of statin therapy | journal = The American Journal of Cardiology | volume = 105 | issue = 9 | pages = 1289–1296 | date = May 2010 | pmid = 20403481 | pmc = 2917836 | doi = 10.1016/j.amjcard.2009.12.051 }}</ref> Studies have shown that reducing LDL cholesterol levels by about 38.7&nbsp;mg/dL with the use of statins can reduce cardiovascular disease and stroke risk by about 21%.<ref>{{cite journal | vauthors = Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC, Sperling L, Virani SS, Yeboah J | display-authors = 6 | title = 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines | journal = Circulation | volume = 139 | issue = 25 | pages = e1082–e1143 | date = June 2019 | pmid = 30586774 | pmc = 7403606 | doi = 10.1161/CIR.0000000000000625 }}</ref> Studies have also found that statins reduce atheroma progression.<ref name="Nicholls_2008">{{cite journal | vauthors = Nicholls SJ | title = Rosuvastatin and progression of atherosclerosis | journal = Expert Review of Cardiovascular Therapy | volume = 6 | issue = 7 | pages = 925–933 | date = August 2008 | pmid = 18666843 | doi = 10.1586/14779072.6.7.925 | s2cid = 46419583 }}</ref> As a result, people with a history of cardiovascular disease may derive benefit from statins irrespective of their cholesterol levels (total cholesterol below 5.0&nbsp;mmol/L [193&nbsp;mg/dL]),<ref name="pmid12114036">{{cite journal | title = MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial | journal = Lancet | volume = 360 | issue = 9326 | pages = 7–22 | date = July 2002 | pmid = 12114036 | doi = 10.1016/S0140-6736(02)09327-3 | s2cid = 35836642 | author1 = Heart Protection Study Collaborative Group }}</ref> and in men without cardiovascular disease, there is benefit from lowering abnormally high cholesterol levels ("primary prevention").<ref name="Shepherd_1995">{{cite journal | vauthors = Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ | display-authors = 6 | title = Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group | journal = The New England Journal of Medicine | volume = 333 | issue = 20 | pages = 1301–1307 | date = November 1995 | pmid = 7566020 | doi = 10.1056/NEJM199511163332001 | doi-access = free }}</ref> Primary prevention in women was originally practiced only by extension of the findings in studies on men,<ref name="Grundy_2007">{{cite journal | vauthors = Grundy SM | title = Should women be offered cholesterol lowering drugs to prevent cardiovascular disease? Yes | journal = BMJ | volume = 334 | issue = 7601 | page = 982 | date = May 2007 | pmid = 17494017 | pmc = 1867899 | doi = 10.1136/bmj.39202.399942.AD }}</ref> since, in women, none of the large statin trials conducted prior to 2007 demonstrated a significant reduction in overall mortality or in cardiovascular endpoints.<ref name="Kendrick_2007">{{cite journal | vauthors = Kendrick M | title = Should women be offered cholesterol lowering drugs to prevent cardiovascular disease? No | journal = BMJ | volume = 334 | issue = 7601 | page = 983 | date = May 2007 | pmid = 17494018 | pmc = 1867901 | doi = 10.1136/bmj.39202.397488.AD }}</ref> Meta-analyses have demonstrated significant reductions in all-cause and cardiovascular mortality, without significant heterogeneity by sex.<ref>{{cite journal | vauthors = Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, Westendorp RG, de Craen AJ, Knopp RH, Nakamura H, Ridker P, van Domburg R, Deckers JW | display-authors = 6 | title = The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials | journal = BMJ | volume = 338 | page = b2376 | date = June 2009 | pmid = 19567909 | pmc = 2714690 | doi = 10.1136/bmj.b2376 }}</ref>

{| class="wikitable" style="float:right"
|+Risk for heart disease
|-
! bgcolor ="#cccccc" colspan=2| Level
! bgcolor ="#cccccc" rowspan=2| Interpretation
|-
! bgcolor ="#cccccc"| [[Milligram|mg]]/[[Decilitre|dL]]
! bgcolor ="#cccccc"| [[Mole (unit)|mmol]]/[[Litre|L]]
|-
| < 200
| < 5.2
| Desirable level<br />(lower risk)
|-
| 200–240
| 5.2–6.2
| Borderline high risk
|-
| > 240
| > 6.2
| High risk
|}

The 1987 report of [[National Cholesterol Education Program]], Adult Treatment Panels suggests the total blood cholesterol level should be: < 200&nbsp;mg/dL normal blood cholesterol, 200–239&nbsp;mg/dL borderline-high, > 240&nbsp;mg/dL high cholesterol.<ref name="pmid3422148">{{cite journal | title = Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. The Expert Panel | journal = Archives of Internal Medicine | volume = 148 | issue = 1 | pages = 36–69 | date = January 1988 | pmid = 3422148 | doi = 10.1001/archinte.148.1.36 }}</ref> The [[American Heart Association]] provides a similar set of guidelines for total (fasting) blood cholesterol levels and risk for heart disease:<ref name=aha-prev/> Statins are effective in lowering LDL cholesterol and widely used for [[primary prevention]] in people at high risk of cardiovascular disease, as well as in [[secondary prevention]] for those who have developed cardiovascular disease.<ref name="AlenghatDavis2019">{{cite journal | vauthors = Alenghat FJ, Davis AM | title = Management of Blood Cholesterol | journal = JAMA | volume = 321 | issue = 8 | pages = 800–801 | date = February 2019 | pmid = 30715135 | pmc = 6679800 | doi = 10.1001/jama.2019.0015 }}</ref>

More current testing methods determine LDL ("bad") and HDL ("good") cholesterol separately, allowing cholesterol analysis to be more nuanced. The desirable LDL level is considered to be less than 100&nbsp;mg/dL (2.6 [[Mole (unit)|mmol]]/L).<ref name=AHA>{{cite web|title= How To Get Your Cholesterol Tested|url=https://www.heart.org/en/health-topics/cholesterol/how-to-get-your-cholesterol-tested |publisher=American Heart Association|date=2023|accessdate=23 August 2023 }}</ref><ref name=CDC>{{cite web|url=https://www.cdc.gov/cholesterol/cholesterol_screening.htm |title=About cholesterol |date=20 March 2023 |publisher=US Centers for Disease Control and Prevention|accessdate=23 August 2023 }}</ref>

[[File:Blood values sorted by mass and molar concentration.png|thumb|center|600px|[[Reference ranges for blood tests]], showing usual, as well as optimal, levels of HDL, LDL, and total cholesterol in mass and molar concentrations, is found in orange color at right, that is, among the blood constituents with the highest concentration.]]

Total cholesterol is defined as the sum of HDL, LDL, and VLDL. Usually, only the total, HDL, and triglycerides are measured. For cost reasons, the VLDL is usually estimated as one-fifth of the triglycerides and the LDL is estimated using the Friedewald formula (or a [[Low-density lipoprotein#Estimation of LDL particles via cholesterol content|variant]]): estimated LDL = [total cholesterol] − [total HDL] − [estimated VLDL]. Direct LDL measures are used when triglycerides exceed 400&nbsp;mg/dL. The estimated VLDL and LDL have more error when triglycerides are above 400&nbsp;mg/dL.<ref name="Warnick_1990">{{cite journal | vauthors = Warnick GR, Knopp RH, Fitzpatrick V, Branson L | title = Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints | journal = Clinical Chemistry | volume = 36 | issue = 1 | pages = 15–19 | date = January 1990 | pmid = 2297909 | doi = 10.1093/clinchem/36.1.15 | doi-access = free }}</ref>

In the [[Framingham Heart Study]], each 10&nbsp;mg/dL (0.6 [[Mole (unit)|mmol]]/L) increase in total cholesterol levels increased 30-year overall mortality by 5% and CVD mortality by 9%. While subjects over the age of 50 had an 11% increase in overall mortality, and a 14% increase in cardiovascular disease mortality per 1&nbsp;mg/dL (0.06 [[Mole (unit)|mmol]]/L) year drop in total cholesterol levels. The researchers attributed this phenomenon to [[Correlation does not imply causation|a different correlation]], whereby the disease itself increases risk of death, as well as changes a myriad of factors, such as weight loss and the inability to eat, which lower serum cholesterol.<ref name="Anderson_1987">{{cite journal | vauthors = Anderson KM, Castelli WP, Levy D | url=https://jamanetwork.com/journals/jama/article-abstract/365739 | title = Cholesterol and mortality. 30 years of follow-up from the Framingham study | journal = JAMA | volume = 257 | issue = 16 | pages = 2176–2180 | date = 24 April 1987 | pmid = 3560398 | doi = 10.1001/jama.1987.03390160062027 }}</ref> This effect was also shown in men of all ages and women over 50 in the Vorarlberg Health Monitoring and Promotion Programme. These groups were more likely to die of cancer, liver diseases, and mental diseases with very low total cholesterol, of 186&nbsp;mg/dL (10.3 [[Mole (unit)|mmol]]/L) and lower. This result indicates the low-cholesterol effect occurs even among younger respondents, contradicting the previous assessment among cohorts of older people that this is a marker for frailty occurring with age.<ref name="Ulmer_2004">{{cite journal | vauthors = Ulmer H, Kelleher C, Diem G, Concin H | title = Why Eve is not Adam: prospective follow-up in 149650 women and men of cholesterol and other risk factors related to cardiovascular and all-cause mortality | journal = Journal of Women's Health | volume = 13 | issue = 1 | pages = 41–53 | year = 2004 | pmid = 15006277 | doi = 10.1089/154099904322836447 }}</ref>

===Hypocholesterolemia===
Abnormally low levels of cholesterol are termed ''[[hypocholesterolemia]]''. Research into the causes of this state is relatively limited, but some studies suggest a link with [[depression (mood)|depression]], [[cancer]], and [[cerebral hemorrhage]]. In general, the low cholesterol levels seem to be a consequence, rather than a cause, of an underlying illness.<ref name="Lewington_2007" /> A genetic defect in cholesterol synthesis causes [[Smith–Lemli–Opitz syndrome]], which is often associated with low plasma cholesterol levels. [[Hyperthyroidism]], or any other endocrine disturbance which causes upregulation of the [[LDL receptor]], may result in hypocholesterolemia.<ref>{{cite journal |vauthors=Rizos CV, Elisaf MS, Liberopoulos EN |title=Effects of thyroid dysfunction on lipid profile |journal=The Open Cardiovascular Medicine Journal |volume=5 |issue=1 |pages=76–84 |date=24 February 2011 |pmid=21660244 |pmc=3109527 |doi= 10.2174/1874192401105010076 |doi-access=free}}</ref>

===Testing===
The [[American Heart Association]] recommends testing cholesterol every 4–6 years for people aged 20 years or older.<ref name="urlHow To Get Your Cholesterol Tested">{{cite web |url=http://www.heart.org/HEARTORG/Conditions/Cholesterol/SymptomsDiagnosisMonitoringofHighCholesterol/How-To-Get-Your-Cholesterol-Tested_UCM_305595_Article.jsp |title=How To Get Your Cholesterol Tested |publisher=American Heart Association |access-date=2013-07-10}}</ref> A separate set of [[American Heart Association]] guidelines issued in 2013 indicates that people taking [[statin]] medications should have their cholesterol tested 4–12 weeks after their first dose and then every 3–12 months thereafter.<ref name="mayo" /><ref>{{cite web |url=http://www.cardiosource.org/News-Media/Publications/Cardiology-Magazine/2013/12/Getting-a-Grasp-of-the-Guidelines.aspx |publisher=American College of Cardiology |vauthors=Stone NJ, Robinson J, Goff DC |year=2013 |title=Getting a grasp of the Guidelines |access-date=2 April 2014 |archive-url=https://web.archive.org/web/20140707122736/http://www.cardiosource.org/News-Media/Publications/Cardiology-Magazine/2013/12/Getting-a-Grasp-of-the-Guidelines.aspx |archive-date=7 July 2014 |url-status=dead}}</ref> For men ages 45 to 65 and women ages 55 to 65, a cholesterol test should occur every 1–2 years, and for seniors over age 65, an annual test should be performed.<ref name=mayo/>

A blood sample after 12-hours of [[fasting]] is taken by a [[Health professional|healthcare professional]] from an arm [[vein]] to measure a [[lipid profile]] for a) total cholesterol, b) HDL cholesterol, c) LDL cholesterol, and d) [[triglyceride]]s.<ref name=mlp/><ref name=mayo/> Results may be expressed as "calculated", indicating a calculation of total cholesterol, HDL, and triglycerides.<ref name=mlp/>

Cholesterol is tested to determine for "normal" or "desirable" levels if a person has a total cholesterol of 5.2&nbsp;mmol/L or less (200&nbsp;mg/dL), an HDL value of more than 1&nbsp;mmol/L (40&nbsp;mg/dL, "the higher, the better"), an LDL value of less than 2.6&nbsp;mmol/L (100&nbsp;mg/dL), and a triglycerides level of less than 1.7&nbsp;mmol/L (150&nbsp;mg/dL).<ref name=mayo/><ref name=mlp/> Blood cholesterol in people with lifestyle, aging, or cardiovascular risk factors, such as [[diabetes mellitus]], [[hypertension]], family history of [[coronary artery disease]], or [[angina]], are evaluated at different levels.<ref name=mayo/>

==Interactive pathway map==
{{StatinPathway WP430|highlight=Cholesterol}}

==Cholesteric liquid crystals==
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 it changes colour when its temperature changes. This makes cholesterol derivatives useful for indicating temperature in [[liquid-crystal display]] [[thermometer]]s and in temperature-sensitive paints.{{Citation needed|date=August 2017}}

==Stereoisomers==
[[File:Cholesterol and ent-cholesterol.svg|200px|thumb|right|Natural cholesterol (top) and ''ent''-cholesterol (bottom)]]
Cholesterol has 256 [[stereoisomer]]s that arise from its eight stereocenters, although only two of the stereoisomers have biochemical significance (''nat''-cholesterol and ''ent''-cholesterol, for ''natural'' and ''enantiomer'', respectively),<ref name="Westover_2003">{{cite journal | vauthors = Westover EJ, Covey DF, Brockman HL, Brown RE, Pike LJ | title = Cholesterol depletion results in site-specific increases in epidermal growth factor receptor phosphorylation due to membrane level effects. Studies with cholesterol enantiomers | journal = The Journal of Biological Chemistry | volume = 278 | issue = 51 | pages = 51125–51133 | date = December 2003 | pmid = 14530278 | pmc = 2593805 | doi = 10.1074/jbc.M304332200 | doi-access = free }}</ref><ref name="Kristiana_2012">{{cite journal | vauthors = Kristiana I, Luu W, Stevenson J, Cartland S, Jessup W, Belani JD, Rychnovsky SD, Brown AJ | display-authors = 6 | title = Cholesterol through the looking glass: ability of its enantiomer also to elicit homeostatic responses | journal = The Journal of Biological Chemistry | volume = 287 | issue = 40 | pages = 33897–33904 | date = September 2012 | pmid = 22869373 | pmc = 3460484 | doi = 10.1074/jbc.M112.360537 | doi-access = free }}</ref> and only one occurs naturally (''nat''-cholesterol).

==Additional images==
<gallery>
File:ConversColest.png|Cholesterol units conversion
File:Steroidogenesis.svg|[[Steroidogenesis]], using cholesterol as building material
File:Cholesterol Spacefill.jpeg|[[Space-filling model]] of the Cholesterol molecule
File:Steroid numbering.svg|Numbering of the [[steroid]] nuclei
</gallery>

== See also ==
{{Portal|Biology}}
{{col div|colwidth=30em}}
* [[Arcus senilis]] "Cholesterol ring" in the eyes
* [[Cardiovascular disease]]
* [[Cholesterol embolism]]
* [[Cholesterol total synthesis]]
* [[Familial hypercholesterolemia]]
* [[Hypercholesterolemia]] "High Cholesterol"
* [[Hypocholesterolemia]] "Low Cholesterol"
* [[Janus-faced molecule]]
* [[List of cholesterol in foods]]
* [[Niemann–Pick disease]] Type C
* [[Oxycholesterol]]
* [[Remnant cholesterol]]
{{colend}}

== References ==
{{reflist|30em|refs=

<ref name="mayo">{{cite web |url=https://www.mayoclinic.org/tests-procedures/cholesterol-test/about/pac-20384601 |publisher=Mayo Clinic |date=15 May 2021 |title=Cholesterol test |access-date=2 September 2023}}</ref>

<ref name="mayo food">{{cite web |url=https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/cholesterol/art-20045192 |publisher=Mayo Clinic |date=2023 |title=Cholesterol: Top foods to improve your numbers |access-date=23 August 2023}}</ref>

}}

== External links ==
* {{Commons category-inline}}

{{Vascular diseases}}
{{Sterols}}
{{Cholesterol and steroid intermediates}}
{{Estrogen-related receptor modulators}}
{{GABAA receptor positive allosteric modulators}}
{{Ion channel modulators}}
{{Authority control}}

[[Category:Cholestanes]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:Lipid disorders]]
[[Category:Neurosteroids]]
[[Category:Nutrition]]
[[Category:Receptor agonists]]
[[Category:Sterols]]
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