Lipoproteins: PCSK9 inhibition: practice question

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Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. It prevents PCSK9 from directing LDL receptors to lysosomal degradation, so more receptors recycle to the hepatocyte surface

Proprotein convertase subtilisin/kexin type 9 binds the LDL receptor and targets it for lysosomal destruction after endocytosis. Evolocumab is a monoclonal antibody against PCSK9, so receptors are spared and recycle, which increases LDL uptake by the liver. This is useful in heterozygous familial hypercholesterolaemia that responds poorly to statins.

Option by option

• A. It blocks the intestinal NPC1L1 transporter and reduces cholesterol absorption from the gut

  NPC1L1 blockade is the mechanism of ezetimibe, which the patient already takes.

• B. It prevents PCSK9 from directing LDL receptors to lysosomal degradation, so more receptors recycle to the hepatocyte surface (correct)

  Preserving LDL receptors increases hepatic clearance of LDL from plasma.

• C. It inhibits microsomal triglyceride transfer protein and reduces hepatic VLDL assembly

  Microsomal triglyceride transfer protein inhibition is the mechanism of lomitapide, used in homozygous familial hypercholesterolaemia.

• D. It binds bile acids in the intestine and interrupts their enterohepatic circulation

  Bile acid binding is the mechanism of resins such as cholestyramine.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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