{"id":1848,"date":"2020-08-18T13:26:46","date_gmt":"2020-08-18T13:26:46","guid":{"rendered":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-cholesterol\/"},"modified":"2021-11-15T07:47:01","modified_gmt":"2021-11-15T05:47:01","slug":"synthesis-of-cholesterol","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-cholesterol\/","title":{"rendered":"Synthesis of Cholesterol"},"content":{"rendered":"\n<p class=\"wp-block-paragraph\"><div class=\"intro\"> Cholesterol is found in every cell, playing a major role in maintaining cell membrane flexibility, and in the production of precursors of bile acid and steroid hormones <\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>70-80 % of the cholesterol is present in esterificated form<\/li><li>poorly soluble in water (hydrophobic)<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><\/div><\/p>\n\n\n<span class=\"block-heading\" id=\"header_1\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Mevalonate pathway<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n\n<div id=\"attachment_19175\" class=\"wp-block-image\"><figure class=\"alignright size-large is-resized\"><a href=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17.png\" target=\"_blank\" title=\"Synthesis of Cholesterol\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17-548x1024.png\" alt=\"\" class=\"wp-image-8091\" width=\"274\" height=\"512\" srcset=\"https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17-548x1024.png 548w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17-161x300.png 161w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17-768x1434.png 768w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17-823x1536.png 823w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17-1097x2048.png 1097w, https:\/\/meddists.com\/learn\/wp-content\/uploads\/2021\/11\/LIPID17.png 857w\" sizes=\"auto, (max-width: 274px) 100vw, 274px\" \/><\/a><figcaption><strong>Figure 1. Synthesis of Cholesterol (step by step)<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n<p class=\"has-white-background-color has-background wp-block-paragraph\">The synthesis of cholesterol is also known as the&nbsp;<strong>mevalonate pathway<\/strong>&nbsp;due to the synthesizing mevalonate molecule (<strong>Figure 1<\/strong>).<\/p>\n\n\n\n<p class=\"has-background wp-block-paragraph\" style=\"background-color:#cfffec\">The synthesis occurs<strong> in the cytosol<\/strong>, with some of the enzymes located within the cytosol, and some fixed to the ER.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">We start with Acetyl-CoA,&nbsp; where all carbon originates.<\/p>\n\n\n\n<p class=\"has-background wp-block-paragraph\" style=\"background-color:#c6f6e3\">The synthesis of the ketone bodies is similar to that of the initiation of acetoacetyl-CoA by thiolase from 2 acetyl-CoA and then condensed with an acetyl-CoA by the addition of HMG-CoA synthase to form <strong>HMG-CoA <\/strong>(3-hydroxy- 3-methyl-glutaryl).<\/p>\n\n\n\n<p class=\"has-white-background-color has-background wp-block-paragraph\">This is converted to mevalonic acid by the reduction of an alcoholic OH group, CoA is released (HMG-CoA reductase in ER) \u2013 this is a rate-determining step requiring NADPH.<\/p>\n\n\n\n<p class=\"has-background wp-block-paragraph\" style=\"background-color:#b9f1db\">A<strong> <\/strong>single molecule of cholesterol requires: <br><strong>18 acetyl CoA,\u00a036 ATP\u00a0and\u00a016 NADPH\u00a0(18 ATPs 18 acetyl CoA)<\/strong><\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Regulation<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<p class=\"has-background wp-block-paragraph\" style=\"background-color:#dcecf9\">Cholesterol synthesis is regulated primarily through\u00a0<strong>HMG-CoA reductase, and the product (cholesterol) itself is<\/strong> the main regulator \u2014 inhibiting the synthesis.<\/p>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"pure-table\"><tbody><tr><td>Some hormones can inhibit the synthesis \u2014\u00a0<strong>insulin<\/strong>,\u00a0<strong>glucagon,\u00a0<\/strong>and\u00a0<strong>cortisol<\/strong><\/td><\/tr><tr><td>Phosphorylation of the enzymes inhibits synthesis, while <strong>dephosphorylation activates it<\/strong><\/td><\/tr><tr><td>Intracellular cholesterol can be reduced by bile acids, leading to increased synthesis<\/td><\/tr><tr><td><em>Cholesterol synthesis is highest at midnight<\/em><\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h2 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">References<\/h2>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<p class=\"wp-block-paragraph\">S<span style=\"font-size: revert; color: initial;\">nider MDS. Devlin\u2019s <strong>Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley &amp; Sons, Incorporated, 2020; 2019.<\/span>  <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Mevalonate pathway<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">Regulation<\/h2><h2 class=\"wp-block-heading\" class=\"wp-block-heading\">References<\/h2><\/div>","protected":false},"excerpt":{"rendered":"<p>Mevalonate pathway The synthesis of cholesterol is also known as the&nbsp;mevalonate pathway&nbsp;due to the synthesizing mevalonate molecule (Figure 1). The synthesis occurs in the cytosol, with some of the enzymes located within the cytosol, and some fixed to the ER. We start with Acetyl-CoA,&nbsp; where all carbon originates. The synthesis of the ketone bodies is [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":1712,"menu_order":11,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1848","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Synthesis of Cholesterol &#8211; Meddists<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-cholesterol\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/meddists.com\\\/learn\\\/pre-clinical\\\/biochemistry\\\/biochemistry-of-the-metabolism\\\/lipid-metabolism\\\/synthesis-of-cholesterol\\\/\",\"url\":\"https:\\\/\\\/meddists.com\\\/learn\\\/pre-clinical\\\/biochemistry\\\/biochemistry-of-the-metabolism\\\/lipid-metabolism\\\/synthesis-of-cholesterol\\\/\",\"name\":\"Synthesis of Cholesterol &#8211; 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