Feedback inhibition of cholesterol synthesis and uptake

✍ Scribed by John C. Stanley

• Book ID: 102468261
• Publisher: Wiley (John Wiley & Sons)
• Year: 2008
• Tongue: English
• Weight: 135 KB
• Volume: 20
• Category: Article
• ISSN: 0956-666X
• DOI: 10.1002/lite.200700098

✦ Synopsis

Abstract

Cells can obtain the cholesterol they need for membrane function either by synthesizing it or by taking it up from the circulation. Both processes are regulated by feedback inhibition. The capacity for synthesis can be changed by changing the amount of the enzyme HMG‐CoA reductase while the capacity for uptake can be changed by changing the amount of the LDL receptor. Transcription factors called SREBPs regulate synthesis of both proteins. SREBPs are synthesized as inactive precursors which are retained in the endoplasmic reticulum (er) when membrane cholesterol levels are high. However, when membrane cholesterol levels begin to fall SREBPs are released from the er, activated in the Golgi apparatus and stimulate the synthesis of both proteins in the nucleus. The Nobel Prize winners Michael Brown and Joseph Goldstein have established the molecular mechanism for this example of feedback inhibition. This has led to the discovery of cellular proteins such as SCAP which can monitor membrane cholesterol content.