HMG-CoA reductase catalyzes the rate-limiting step in cholesterol biosynthesis. Its activity is regulated at multiple levels. Which of the following represents post-translational regulation of this enzyme?

• A Insulin increases HMG-CoA reductase mRNA transcription via SREBP-2
• B Statins competitively inhibit the enzyme by mimicking mevalonate
• C Bile acids suppress CYP7A1, reducing cholesterol conversion to bile salts
• D Sterols accelerate ERAD-mediated degradation of HMG-CoA reductase protein ✓

Explanation

HMG-CoA reductase undergoes post-translational regulation by accelerated proteasomal degradation when cellular sterols are high. Sterols signal the retention of INSIG proteins in the ER, which recruit the gp78 E3 ubiquitin ligase to ubiquitinate HMG-CoA reductase, targeting it for ERAD (ER-associated degradation). This is a rapid, post-translational mechanism distinct from transcriptional regulation by SREBP-2 (which is a transcriptional mechanism). Statin inhibition is pharmacological competitive inhibition, not physiological post-translational control.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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