Editing Cholesterol (section)

===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|access-date=19 September 2013|archive-date=7 January 2018|archive-url=https://web.archive.org/web/20180107234818/http://pharmaxchange.info/press/2013/09/biosynthesis-and-regulation-of-cholesterol-animation/|url-status=dead}}</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).{{cn|date=December 2024}}

[[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>