A 44-year-old man sustains a myocardial infarction, and is admitted to the hospital from the emergency room. Serum chemistries reveal two-fold elevation of his LDL cholesterol. He is prescribed lovastatin, which acts by inhibiting which of the following enzymes?
Hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase) catalyzes the rate-limiting step in cholesterol synthesis, in which HMG-CoA (formed from 3 acetyl-CoA molecules) is reduced to mevalonic acid, using 2 NADPH. Lovastatin and pravastatin reduce cholesterol synthesis and lower serum cholesterol levels by inhibiting this enzyme. Lovastatin is metabolized by the CYP3A isoform of cytochrome P450. In contrast, gemfibrozil and clofibrate lower cholesterol by increasing the activity of lipoprotein lipase, which is produced by the endothelial cells of the vasculature of adipose and muscle tissue. Acetyl-CoA carboxylase catalyzes the first step in fatty acid synthesis. Carbamoyl phosphate synthetase catalyzes the rate-limiting step in urea synthesis. Pyruvate dehydrogenase catalyzes the transition step between glycolysis and the TCA (Krebs) cycle. Ref: Baron R.B. (2013). Chapter 28. Lipid Disorders. In M.A. Papadakis, S.J. McPhee, M.W. Rabow (Eds), CURRENT Medical Diagnosis & Treatment 2013.
Acetyl-CoA carboxylase
Carbamoyl phosphate synthetase I
Hydroxymethyl glutaryl-CoA reductase
Pyruvate dehydrogenase