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

Acetoacetyl-CoA thiolase

hydroxymethylglutaryl-CoA synthase or HMG-CoA synthase; EC 2.3.3.10

HMG-CoA Reductase

Mevalonate kinase

Phosphomevalonate kinase

  • The Crystal Structure of Human Phosphomavelonate Kinase At 1.8 A Resolution 3ch4

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


Crystal Structure of HMG-CoA, (PDB code 1dq8)

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ReferencesReferences

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Alexander Berchansky