How is HMG-CoA reductase activity regulated?

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Multiple Choice

How is HMG-CoA reductase activity regulated?

HMG-CoA reductase is controlled both by its phosphorylation state and by transcriptional signals that respond to cholesterol levels. When energy is low, AMP-activated protein kinase (AMPK) phosphorylates the enzyme and inactivates it, slowing cholesterol synthesis to conserve energy. At the same time, cholesterol levels feed back on transcription through SREBP-2: when cholesterol is scarce, SREBP-2 is activated and promotes transcription of HMG-CoA reductase, boosting production; when cholesterol is abundant, SREBP-2 processing is inhibited, reducing transcription. This combination—rapid, post-translational inhibition by AMPK and longer-term transcriptional regulation via the SREBP pathway—accurately describes how the enzyme’s activity is regulated.

HMG-CoA reductase is controlled both by its phosphorylation state and by transcriptional signals that respond to cholesterol levels. When energy is low, AMP-activated protein kinase (AMPK) phosphorylates the enzyme and inactivates it, slowing cholesterol synthesis to conserve energy. At the same time, cholesterol levels feed back on transcription through SREBP-2: when cholesterol is scarce, SREBP-2 is activated and promotes transcription of HMG-CoA reductase, boosting production; when cholesterol is abundant, SREBP-2 processing is inhibited, reducing transcription. This combination—rapid, post-translational inhibition by AMPK and longer-term transcriptional regulation via the SREBP pathway—accurately describes how the enzyme’s activity is regulated.

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