Biosynthesis of cholesterol
Synthesis within the body starts with the mevalonate pathway where two molecules of acetyl CoA condense to form acetoacetyl-CoA. This is followed by a second condensation between acetyl CoA and acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. Production of mevalonate is the rate-limiting and irreversible step in cholesterol synthesis and is the site of action for statins. Acetyl-CoA is coming from Citric Acid Cycle. Mevalonate pathway Step 1 Acetoacetyl-CoA thiolase Step 2 hydroxymethylglutaryl-CoA synthase or HMG-CoA synthase; EC 2.3.3.10 Step 3 HMG-CoA Reductase Step 4 Mevalonate kinase Step 5 Phosphomevalonate kinase
Step 6 Mevalonate-5-pyrophosphate decarboxylase Diphosphomevalonate decarboxylase (EC 4.1.1.33), most commonly referred to in scientific literature as mevalonate diphosphate decarboxylase.
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