{"id":543,"date":"2017-10-26T14:40:04","date_gmt":"2017-10-26T14:40:04","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/sunynutrition\/?post_type=chapter&#038;p=543"},"modified":"2017-11-13T20:05:58","modified_gmt":"2017-11-13T20:05:58","slug":"6-35-cholesterol-synthesis","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/chapter\/6-35-cholesterol-synthesis\/","title":{"raw":"6.35 Cholesterol Synthesis","rendered":"6.35 Cholesterol Synthesis"},"content":{"raw":"<div class=\"AHA Heart Attack Risk Assessment - http:\/\/www.heart.org\/HEARTORG\/Conditions\/HeartAttack\/HeartAttackToolsResources\/Heart-Attack-Risk-Assessment_UCM_303944_Article.jsp#.WKy1vjsrJaRDashing Hopes, Study Shows a Cholesterol Drug Had No Effect on Heart Health - http:\/\/www.nytimes.com\/2016\/04\/04\/health\/dashing-hopes-study-shows-cholesterol-drug-has-no-benefits.html?Tests of Cholesterol Drugs Offer Hope of Reducing Heart Attacks and Strokes - www.nytimes.com\/2015\/03\/16\/business\/tests-of-cholesterol-drugs-offer-hope-of-reducing-heart-attacks-and-strokes.html?\">\r\n\r\nAcetyl-CoA is also used to synthesize cholesterol. As shown below, there are a large number of reactions and enzymes involved in cholesterol synthesis.\r\n<div>\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"461\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/2569\/2017\/10\/26143848\/10000000000001CD0000025887014678.png\" alt=\"\" width=\"461\" height=\"600\" \/> Figure 6.351 Cholesterol synthesis pathway<sup>1<\/sup>[\/caption]\r\n\r\n<\/div>\r\nSimplifying this, acetyl-CoA is converted to acetoacetyl-CoA (4 carbons) before forming 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA is converted to mevalonate by the enzyme HMG-CoA reductase. This enzyme is important because it is the rate-limiting enzyme in cholesterol synthesis.\r\n<div>\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"1140\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/2569\/2017\/10\/26143850\/100000000000047400000296B4A9B457.png\" alt=\"\" width=\"1140\" height=\"662\" \/> Figure 6.352 Cholesterol synthesis simplified<sup>2<\/sup>[\/caption]\r\n\r\n<\/div>\r\nA rate-limiting enzyme is like a bottleneck in a highway, as shown below, that determines the flow of traffic past it.\r\n<div>\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"451\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/2569\/2017\/10\/26143851\/10000201000001C300000257BB9F655F.png\" alt=\"\" width=\"451\" height=\"599\" \/> Figure 6.353 Bottleneck in traffic<sup>3<\/sup>[\/caption]\r\n\r\n<\/div>\r\nRate-limiting enzymes limit the rate at which a metabolic pathway proceeds. The pharmaceutical industry has taken advantage of this knowledge to lower people's LDL levels with drugs known as statins. These drugs inhibit HMG-CoA reductase and thus decrease cholesterol synthesis. Less cholesterol leads to lower LDL levels, and hopefully a lower risk of cardiovascular disease.\r\n\r\nThe brand name of the statins approved for use in the US are<sup>4<\/sup>:\r\n<ul>\r\n \t<li>Lipitor<\/li>\r\n \t<li>Lescol<\/li>\r\n \t<li>Mevacor<\/li>\r\n \t<li>Pravachol<\/li>\r\n \t<li>Crestor<\/li>\r\n \t<li>Zocor<\/li>\r\n \t<li>Livalo<\/li>\r\n<\/ul>\r\nThe first link below talks about the new cholesterol guidelines, in which statins are prescribed at set therapeutic doses based on assessed cardiovascular risk rather than treating LDL and HDL to target levels. The second link is to the online calculator that can be used to estimate individual\u2019s risk based on results from the Framingham Heart Study. The third link talks about a drug that was effective at lowering LDL, increasing HDL, but did not improve cardiovascular disease outcomes. This finding is consistent with the new cholesterol guidelines deemphasizing HDL and LDL target levels. The fourth link below describes some new cholesterol lowering drugs, which have shown some promising preliminary results.\r\n<table><colgroup> <col \/><\/colgroup>\r\n<tbody>\r\n<tr>\r\n<td><b>Web Links<\/b>\r\n\r\n<a href=\"http:\/\/well.blogs.nytimes.com\/2013\/11\/12\/3-things-to-know-about-the-new-cholesterol-guidelines\/?\"><u>3 Things to Know About the New Cholesterol Guidelines<\/u><\/a>\r\n\r\n<a href=\"http:\/\/www.heart.org\/HEARTORG\/Conditions\/HeartAttack\/HeartAttackToolsResources\/Heart-Attack-Risk-Assessment_UCM_303944_Article.jsp#.WKy1vjsrJaR\"><u>AHA Heart Attack Risk Assessment<\/u><\/a>\r\n\r\n<a href=\"http:\/\/www.nytimes.com\/2016\/04\/04\/health\/dashing-hopes-study-shows-cholesterol-drug-has-no-benefits.html?partner=rss&amp;emc=rss&amp;_r=0\"><u>Dashing Hopes, Study Shows a Cholesterol Drug Had No Effect on Heart Health<\/u><\/a>\r\n\r\n<a href=\"http:\/\/www.nytimes.com\/2015\/03\/16\/business\/tests-of-cholesterol-drugs-offer-hope-of-reducing-heart-attacks-and-strokes.html?\"><u>Tests of Cholesterol Drugs Offer Hope of Reducing Heart Attacks and Strokes<\/u><\/a>-<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\nThe body synthesizes approximately 1 gram of cholesterol a day, whereas it is recommended that we consume less than 0.3 gram a day. A number of tissues synthesize cholesterol, with the liver accounting for ~20% of synthesis. The intestine is believed to be the most active among the other tissues that are responsible for the other 80% of cholesterol synthesis<sup>5<\/sup>.\r\n\r\n<b>References &amp; Links<\/b>\r\n\r\n1. https:\/\/en.wikipedia.org\/wiki\/Statin#\/media\/File:HMG-CoA_reductase_pathway.png\r\n\r\n2. http:\/\/en.wikipedia.org\/wiki\/File:Squalene.svg\r\n\r\n3. http:\/\/en.wikipedia.org\/wiki\/File:Bottleneck.svg\r\n\r\n4. http:\/\/www.medicinenet.com\/statins\/page3.htm\r\n\r\n5. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.\r\n\r\n<b>Links<\/b>\r\n\r\n3 Things to Know About the New Cholesterol Guidelines - http:\/\/well.blogs.nytimes.com\/2013\/11\/12\/3-things-to-know-about-the-new-cholesterol-guidelines\/\r\n\r\n<\/div>","rendered":"<div class=\"AHA Heart Attack Risk Assessment - http:\/\/www.heart.org\/HEARTORG\/Conditions\/HeartAttack\/HeartAttackToolsResources\/Heart-Attack-Risk-Assessment_UCM_303944_Article.jsp#.WKy1vjsrJaRDashing Hopes, Study Shows a Cholesterol Drug Had No Effect on Heart Health - http:\/\/www.nytimes.com\/2016\/04\/04\/health\/dashing-hopes-study-shows-cholesterol-drug-has-no-benefits.html?Tests of Cholesterol Drugs Offer Hope of Reducing Heart Attacks and Strokes - www.nytimes.com\/2015\/03\/16\/business\/tests-of-cholesterol-drugs-offer-hope-of-reducing-heart-attacks-and-strokes.html?\">\n<p>Acetyl-CoA is also used to synthesize cholesterol. As shown below, there are a large number of reactions and enzymes involved in cholesterol synthesis.<\/p>\n<div>\n<div style=\"width: 471px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/2569\/2017\/10\/26143848\/10000000000001CD0000025887014678.png\" alt=\"\" width=\"461\" height=\"600\" \/><\/p>\n<p class=\"wp-caption-text\">Figure 6.351 Cholesterol synthesis pathway<sup>1<\/sup><\/p>\n<\/div>\n<\/div>\n<p>Simplifying this, acetyl-CoA is converted to acetoacetyl-CoA (4 carbons) before forming 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA is converted to mevalonate by the enzyme HMG-CoA reductase. This enzyme is important because it is the rate-limiting enzyme in cholesterol synthesis.<\/p>\n<div>\n<div style=\"width: 1150px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/2569\/2017\/10\/26143850\/100000000000047400000296B4A9B457.png\" alt=\"\" width=\"1140\" height=\"662\" \/><\/p>\n<p class=\"wp-caption-text\">Figure 6.352 Cholesterol synthesis simplified<sup>2<\/sup><\/p>\n<\/div>\n<\/div>\n<p>A rate-limiting enzyme is like a bottleneck in a highway, as shown below, that determines the flow of traffic past it.<\/p>\n<div>\n<div style=\"width: 461px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/2569\/2017\/10\/26143851\/10000201000001C300000257BB9F655F.png\" alt=\"\" width=\"451\" height=\"599\" \/><\/p>\n<p class=\"wp-caption-text\">Figure 6.353 Bottleneck in traffic<sup>3<\/sup><\/p>\n<\/div>\n<\/div>\n<p>Rate-limiting enzymes limit the rate at which a metabolic pathway proceeds. The pharmaceutical industry has taken advantage of this knowledge to lower people&#8217;s LDL levels with drugs known as statins. These drugs inhibit HMG-CoA reductase and thus decrease cholesterol synthesis. Less cholesterol leads to lower LDL levels, and hopefully a lower risk of cardiovascular disease.<\/p>\n<p>The brand name of the statins approved for use in the US are<sup>4<\/sup>:<\/p>\n<ul>\n<li>Lipitor<\/li>\n<li>Lescol<\/li>\n<li>Mevacor<\/li>\n<li>Pravachol<\/li>\n<li>Crestor<\/li>\n<li>Zocor<\/li>\n<li>Livalo<\/li>\n<\/ul>\n<p>The first link below talks about the new cholesterol guidelines, in which statins are prescribed at set therapeutic doses based on assessed cardiovascular risk rather than treating LDL and HDL to target levels. The second link is to the online calculator that can be used to estimate individual\u2019s risk based on results from the Framingham Heart Study. The third link talks about a drug that was effective at lowering LDL, increasing HDL, but did not improve cardiovascular disease outcomes. This finding is consistent with the new cholesterol guidelines deemphasizing HDL and LDL target levels. The fourth link below describes some new cholesterol lowering drugs, which have shown some promising preliminary results.<\/p>\n<table>\n<colgroup>\n<col \/><\/colgroup>\n<tbody>\n<tr>\n<td><b>Web Links<\/b><\/p>\n<p><a href=\"http:\/\/well.blogs.nytimes.com\/2013\/11\/12\/3-things-to-know-about-the-new-cholesterol-guidelines\/?\"><u>3 Things to Know About the New Cholesterol Guidelines<\/u><\/a><\/p>\n<p><a href=\"http:\/\/www.heart.org\/HEARTORG\/Conditions\/HeartAttack\/HeartAttackToolsResources\/Heart-Attack-Risk-Assessment_UCM_303944_Article.jsp#.WKy1vjsrJaR\"><u>AHA Heart Attack Risk Assessment<\/u><\/a><\/p>\n<p><a href=\"http:\/\/www.nytimes.com\/2016\/04\/04\/health\/dashing-hopes-study-shows-cholesterol-drug-has-no-benefits.html?partner=rss&amp;emc=rss&amp;_r=0\"><u>Dashing Hopes, Study Shows a Cholesterol Drug Had No Effect on Heart Health<\/u><\/a><\/p>\n<p><a href=\"http:\/\/www.nytimes.com\/2015\/03\/16\/business\/tests-of-cholesterol-drugs-offer-hope-of-reducing-heart-attacks-and-strokes.html?\"><u>Tests of Cholesterol Drugs Offer Hope of Reducing Heart Attacks and Strokes<\/u><\/a>&#8211;<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<p>The body synthesizes approximately 1 gram of cholesterol a day, whereas it is recommended that we consume less than 0.3 gram a day. A number of tissues synthesize cholesterol, with the liver accounting for ~20% of synthesis. The intestine is believed to be the most active among the other tissues that are responsible for the other 80% of cholesterol synthesis<sup>5<\/sup>.<\/p>\n<p><b>References &amp; Links<\/b><\/p>\n<p>1. https:\/\/en.wikipedia.org\/wiki\/Statin#\/media\/File:HMG-CoA_reductase_pathway.png<\/p>\n<p>2. http:\/\/en.wikipedia.org\/wiki\/File:Squalene.svg<\/p>\n<p>3. http:\/\/en.wikipedia.org\/wiki\/File:Bottleneck.svg<\/p>\n<p>4. http:\/\/www.medicinenet.com\/statins\/page3.htm<\/p>\n<p>5. Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.<\/p>\n<p><b>Links<\/b><\/p>\n<p>3 Things to Know About the New Cholesterol Guidelines &#8211; http:\/\/well.blogs.nytimes.com\/2013\/11\/12\/3-things-to-know-about-the-new-cholesterol-guidelines\/<\/p>\n<\/div>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-543\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>Kansas State University Human Nutrition Flexbook. <strong>Authored by<\/strong>: Brian Lindshield. <strong>Provided by<\/strong>: Kansas State University. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"http:\/\/goo.gl\/vOAnR\">http:\/\/goo.gl\/vOAnR<\/a>. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">CC BY: Attribution<\/a><\/em><\/li><\/ul><\/div>\n\t\t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t <\/section>","protected":false},"author":44985,"menu_order":18,"template":"","meta":{"_candela_citation":"[{\"type\":\"cc\",\"description\":\"Kansas State University Human Nutrition Flexbook\",\"author\":\"Brian Lindshield\",\"organization\":\"Kansas State University\",\"url\":\"goo.gl\/vOAnR\",\"project\":\"\",\"license\":\"cc-by\",\"license_terms\":\"\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-543","chapter","type-chapter","status-publish","hentry"],"part":442,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/pressbooks\/v2\/chapters\/543","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/wp\/v2\/users\/44985"}],"version-history":[{"count":6,"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/pressbooks\/v2\/chapters\/543\/revisions"}],"predecessor-version":[{"id":1735,"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/pressbooks\/v2\/chapters\/543\/revisions\/1735"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/pressbooks\/v2\/parts\/442"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/pressbooks\/v2\/chapters\/543\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/wp\/v2\/media?parent=543"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/pressbooks\/v2\/chapter-type?post=543"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/wp\/v2\/contributor?post=543"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-herkimer-nutritionflex\/wp-json\/wp\/v2\/license?post=543"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}