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Biochemistry · Cholesterol metabolism: HMG-CoA reductase
Sample itemIn a sterol-depleted hepatocyte, SREBP-2 travels to the Golgi, is cleaved, and enters the nucleus. Transcription of the LDL receptor gene rises, along with that of which rate-limiting enzyme of cholesterol synthesis?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. HMG-CoA reductase
SREBP-2 is the sterol-responsive transcription factor and upregulates both LDL receptor uptake and cholesterol synthesis genes, chiefly the rate-limiting enzyme. Statins use this loop, because lower sterol content triggers SREBP-2 and more LDL receptors. ACAT is not induced because there is no cholesterol excess to store.
Option by option
A. Acyl-CoA cholesterol acyltransferase
Cholesterol esterification would be reduced, not induced, when sterol content is low.
B. Lanosterol synthase
Lanosterol synthase is not the rate-limiting enzyme of the pathway.
C. Squalene epoxidase
Squalene epoxidase is a late enzyme and is not the principal SREBP-2 target for flux control.
D. HMG-CoA reductase (correct)
Correct. SREBP-2 raises transcription of this rate-limiting enzyme together with the LDL receptor.
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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