A 50-year-old woman with hypothyroidism is found to have elevated LDL cholesterol. Thyroid hormone normally upregulates hepatic LDL receptor expression. In her hypothyroid state, LDL clearance is reduced. Which intracellular mechanism, when LDL enters a cell via its receptor, normally prevents cholesterol overload?

• A LDL-cholesterol activates SREBP-2, which increases HMG-CoA reductase transcription
• B LDL-cholesterol suppresses SREBP-2 processing and reduces HMG-CoA reductase expression, while activating ACAT to esterify excess cholesterol ✓
• C LDL-cholesterol is directly exported from the cell by ABCA1 transporters
• D LDL-cholesterol inhibits lysosomal acid lipase, preventing release of free cholesterol from LDL

Explanation

When LDL is internalized via receptor-mediated endocytosis and lysosomes release free cholesterol, intracellular cholesterol homeostasis is maintained through three coordinated responses: (1) suppression of SREBP-2 cleavage, reducing HMG-CoA reductase transcription (less de novo synthesis); (2) activation of ACAT (acyl-CoA:cholesterol acyltransferase) to esterify and store excess cholesterol; and (3) downregulation of LDL receptor expression. This triple regulation prevents cellular cholesterol overload.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.