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

• Acetoacetyl-CoA thiolase

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

• 1xpk

HMG-CoA Reductase

• HMG-CoA Reductase

Mevalonate kinase

• 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.

• Mevalonate Diphosphate Decarboxylase

Isopentenyl pyrophosphate isomerase

Isopentenyl pyrophosphate isomerase (EC 5.3.3.2, IPP isomerase), also known as Isopentenyl-diphosphate delta isomerase

• Isopentenyl-diphosphate delta-isomerase

Mevalonate is finally converted to isopentenyl pyrophosphate.

Geranyl transferase

Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase.

• Farnesyl diphosphate synthase