Cholesterol biosynthesis,



All animal cells manufacture cholesterol with relative production rates varying by cell type and organ function. About 20–25% of total daily cholesterol production occurs in the liver; other sites of higher synthesis rates include the intestines, adrenal glands, and reproductive organs. Synthesis within the body starts with one molecule of acetyl CoA and one molecule of acetoacetyl-CoA, which are hydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA).[34] This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. This is the regulated, rate-limiting and irreversible step in cholesterol synthesis and is the site of action for the statin drugs (HMG-CoA reductase competitive inhibitors).

Mevalonate is then converted to 3-isopentenyl pyrophosphate in three reactions that require ATP. Mevalonate is decarboxylated to isopentenyl pyrophosphate, which is a key metabolite for various biological reactions. Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum.[34] Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Finally, lanosterol is converted to cholesterol through a 19-step process.[35][36]

Konrad Bloch and Feodor Lynen shared the Nobel Prize in Physiology or Medicine in 1964 for their discoveries concerning the mechanism and regulation of cholesterol and fatty acid metabolism.


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