{"id":1851,"date":"2020-08-18T13:29:51","date_gmt":"2020-08-18T13:29:51","guid":{"rendered":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-ketone-bodies\/"},"modified":"2021-11-17T00:25:37","modified_gmt":"2021-11-16T22:25:37","slug":"synthesis-of-ketone-bodies","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/pre-clinical\/biochemistry\/biochemistry-of-the-metabolism\/lipid-metabolism\/synthesis-of-ketone-bodies\/","title":{"rendered":"Synthesis of Ketone bodies"},"content":{"rendered":"\n

Ketone Body Synthesis and Utilisation<\/h3>\n<\/span>\n\n\n

The ketone bodies that could supply energy in different tissues are acetone<\/strong>, acetoacetate<\/strong>, and \u00df-hydroxybutyrate<\/strong>. <\/div><\/p>\n\n\n\n

The synthesis of ketone bodies goes through the initial mevalonate pathway until HGM-CoA is produced (Figure 1<\/strong>).<\/p>\n\n\n<\/span>\n

Ketone body synthesis<\/h2>\n<\/span>\n\n\n

Ketone body synthesis takes place in the mitochondrial matrix and starts with the condensation of two acetyl CoA molecules to form acetoacetyl CoA.<\/p>\n\n\n\n

\"\"<\/a>
Figure 1. Synthesis of ketone bodies<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n

The enzymes involved:<\/p>\n\n\n\n

HMG-CoA synthase<\/strong> catalyzes the condensation of acetoacetyl CoA with another molecule of acetyl CoA to form \u03b2 hydroxy-\u03b2-methyl glutaryl coenzyme A (HMG-CoA)<\/p>\n\n\n\n

HMG CoA lyase<\/strong> then cleaves HMG CoA to yield acetoacetate and acetyl CoA.<\/p>\n\n\n\n

Acetoacetate can instantly get into the blood or could be reduced by a \u03b2-hydroxybutyrate dehydrogenase<\/strong> to \u03b2-hydroxybutyrate, which enters the blood.<\/p>\n\n\n\n

The ratio of \u03b2-hydroxybutyrate to acetoacetate in the blood is around 1:1.<\/em><\/p>\n\n\n\n

Acetone formation is spontaneous and minimal under normal circumstances, but at high concentrations of acetoacetate, which could happen in severe diabetic ketoacidosis, acetone can achieve levels sufficient to be detectable in the breath.<\/p>\n\n\n\n

Acetoacetate and \u03b2-hydroxybutyrate synthesized by the liver cells are perfect energy sources for most non-hepatic tissues.<\/p>\n\n\n\n

During extended fasting, ketone bodies substitute glucose as an energy resource, especially in the brain, which starts to use ketone bodies after 2-3 days of fasting.<\/p>\n\n\n<\/span>\n

Metabolisation of ketone bodies<\/h2>\n<\/span>\n\n\n

Ketone bodies are metabolized in the mitochondria of non-hepatic tissues.<\/p>\n\n\n\n

\"\"<\/a>
Figure 2. Metabolisation of ketone bodies<\/strong><\/figcaption><\/figure><\/div>\n\n\n\n

\u03b2-hydroxybutyrate dehydrogenase<\/strong>\u00a0converts \u03b2-hydroxybutyrate to acetoacetate by NAD-linked oxidation.<\/p>\n\n\n\n

Acetoacetate is then converted by succinyl-CoA transferase<\/strong>, which is present in tissues that use ketone bodies but are not present in the liver. <\/p>\n\n\n\n

Succinyl-CoA can serve as the source of CoA.\u00a0\u03b2-ketothiolase<\/strong>\u00a0converts the acetoacetyl CoA into two acetyls CoAs, which enter the tricarboxylic acid cycle for energy production. <\/p>\n\n\n\n

The energy generated from the oxidation of acetoacetate is equivalent to the yield for oxidation of 2 acetyl CoA in the TCA cycle (20 ATP<\/strong>). <\/p>\n\n\n\n

Oxidation of \u03b2-hydroxybutyrate produces one further NADH. Hence, the net energy yield from one molecule of \u03b2-hydroxybutyrate is around 21.5 molecules of ATP.<\/p>\n\n\n\n

The critical enzymes of ketone body synthesis, HMG-CoA synthase<\/strong> and HMG-CoA lyase<\/strong>, are present in the liver but not in other tissues. The critical enzyme of ketone body utilisation, acetoacetate: succinyl-CoA transferase<\/strong>, is found in many tissues, but not in the liver. These differences ensure that ketone bodies are made in the liver and utilised in other tissues (Figure 2<\/strong>).<\/p>\n\n\n<\/span>\n

References<\/h2>\n<\/span>\n\n\n

Snider MDS. Devlin\u2019s Textbook of Biochemistry with Clinical Correlations<\/strong>, the 8th Edition. John Wiley & Sons, Incorporated, 2020; 2019.<\/span> <\/p>\n<\/span>

Ketone Body Synthesis and Utilisation<\/h3>

Ketone body synthesis<\/h2>

Metabolisation of ketone bodies<\/h2>

References<\/h2><\/div>","protected":false},"excerpt":{"rendered":"

Ketone Body Synthesis and Utilisation The synthesis of ketone bodies goes through the initial mevalonate pathway until HGM-CoA is produced (Figure 1). Ketone body synthesis Ketone body synthesis takes place in the mitochondrial matrix and starts with the condensation of two acetyl CoA molecules to form acetoacetyl CoA. The enzymes involved: HMG-CoA synthase catalyzes the condensation […]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":1712,"menu_order":14,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-1851","page","type-page","status-publish","hentry"],"yoast_head":"\nSynthesis of Ketone bodies – 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-ketone-bodies\/\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" 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