A 45-year-old man with familial hypercholesterolemia has xanthomas and a markedly elevated LDL. He is started on a statin. The primary mechanism by which statins lower plasma LDL is:
- A Competitive inhibition of HMG-CoA reductase, upregulating hepatic LDL receptors ✓
- B Inhibition of intestinal cholesterol absorption
- C Activation of lipoprotein lipase in peripheral tissues
- D Promotion of reverse cholesterol transport by HDL
Correct answer: A. Competitive inhibition of HMG-CoA reductase, upregulating hepatic LDL receptors
Explanation
Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway for cholesterol biosynthesis. Reduced intrahepatic cholesterol synthesis depletes hepatocyte cholesterol pools, triggering SREBP-2-mediated upregulation of LDL receptor expression on hepatocyte surfaces. The increased LDL receptors clear LDL particles from plasma by receptor-mediated endocytosis, lowering circulating LDL cholesterol.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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