Which of the following is the rate limiting step in cholesterol synthesis?
Initially in cholesterol synthesis, two molecules of acetyl-CoA condense to form acetoacetyl-CoA catalyzed by cytosolic thiolase. Acetoacetyl-CoA condenses with a fuher molecule of acetyl-CoA catalyzed by HMG-CoA synthase to form HMG-CoA, which is reduced to mevalonate by NADPH in a reaction catalyzed by HMG-CoA reductase. This last step is the principal regulatory step in the pathway of cholesterol synthesis and is the site of action of the most effective class of cholesterol-lowering drugs, the statins, which are HMG-CoA reductase inhibitors. Ref: Botham K.M., Mayes P.A. (2011). Chapter 26. Cholesterol Synthesis, Transpo, & Excretion. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds), Harper's Illustrated Biochemistry, 29e.
HMG CoA synthase
HMG CoA reductase
Thiokinase
Mevalonate kinase