Biosynthesis of cholesterol
Synthesis within the body starts with the mevalonate pathway where two molecules of condense to form . This is followed by a second condensation between acetyl CoA and acetoacetyl-CoA to form . This molecule is then reduced to 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 Acetoacetyl-CoA thiolase 2 => . Hydroxymethylglutaryl-CoA synthase or HMG-CoA synthase; EC 2.3.3.10 + => . HMG-CoA Reductase Mevalonate kinase Phosphomevalonate kinase
Mevalonate-5-pyrophosphate decarboxylase Diphosphomevalonate decarboxylase (EC 4.1.1.33), most commonly referred to in scientific literature as mevalonate diphosphate decarboxylase. Isopentenyl pyrophosphate isomerase Isopentenyl pyrophosphate isomerase (EC 5.3.3.2, IPP isomerase), also known as Isopentenyl-diphosphate delta isomerase Mevalonate is finally converted to isopentenyl pyrophosphate. Next steps of Cholesterol Biosynthesis Geranyl transferase Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Other names in common use include:
Squalene synthase Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum. Oxidosqualene cyclase Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Finally, lanosterol is converted to cholesterol via either of two pathways, the Bloch pathway, or the Kandutsch-Russell pathway. |
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