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The rate-determining stage in cholesterol production is the conversion of HMG-CoA by HMG-CoA reductase to mevalonate.
Compounds that are successful at lowering serum cholesterol levels target the enzyme HMG-CoA reductase (HMGR).
What is cholesterol synthesis?
Beginning with acetyl-CoA, which is mostly produced from an oxidation event in the mitochondria, the biosynthesis of cholesterol typically occurs in the endoplasmic reticulum of hepatic cells. Acetyl-CoA synthetase can also produce acetyl-CoA via the cytoplasmic oxidation of ethanol.
In a multistep, intricate process, 3-hydroxy-methylglutaryl-CoA reductase (HMG-CoA-R) mediates the rate-limiting stage that catalyzes the conversion of HMG-CoA to mevalonic acid, which is how cholesterol produced from acetyl-CoA.
In both healthy tissues and tumors, both the concentration of cholesterol and the rate of cholesterol biosynthesis are higher. Inhibiting cholesterol biosynthesis prevents cell development, suggesting a connection between cholesterol and DNA synthetic pathways. Cholesterol biosynthesis occurs far earlier than DNA synthesis.
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