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What is Which of the following compounds directly inhibits the expression of the HMG-CoA reductase gene? and explain in detail?
The major regulatory enzyme of cholesterol metabolism, HMG-CoA reductase, is regulated by three distinct mechanisms. The first is phosphorylation by a cAMP dependent protein kinase. Phosphorylation of HMG-CoA reductase inactivates the enzyme. The other two mechanisms involve the levels of cholesterol. The degradation of the enzyme is controlled by cholesterol levels. a) The half-life of HMG-CoA reductase is regulated by cholesterol levels with high concentrations of cholesterol leading to a shoer half-life. b) The final regulatory mechanism involves control of the expression of the HMG-CoA reductase gene. High levels of cholesterol lead to a decrease in the mRNA levels coding for HMG-CoA reductase. 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.