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Updated: Jun 28, 2026
07:54
Cholesterol Efflux Assay
Published on: March 6, 2012
Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL
Michael S Brown1, Joseph L Goldstein
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390-9046, USA. mike.brown@utsouthwestern.edu
Journal of Lipid Research
|November 1, 2008
Summary
Cholesterol synthesis is tightly regulated. Over 75 years, research progressed from basic balance studies to molecular discoveries like sterol regulatory element-binding proteins (SREBPs) and Scap, revealing key feedback mechanisms.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Cholesterol biosynthesis is a highly regulated cellular process.
- Feedback regulation ensures cellular cholesterol homeostasis.
- Historical context traces back 75 years to Rudolf Schoenheimer's studies.
Observation:
- Cholesterol feeding in mice demonstrated feedback inhibition of synthesis.
- Sterol regulatory element-binding proteins (SREBPs) were identified as key regulators.
- Scap, a cholesterol-sensing escort protein, plays a crucial role.
Findings:
- SREBPs mediate feedback regulation of cholesterol synthesis.
- The Scap protein contains a critical sterol-sensing hexapeptide, MELADL.
- The discovery of SREBPs and Scap elucidated the molecular basis of cholesterol feedback.
Implications:
- Understanding cholesterol feedback is vital for membrane biology.
- Insights impact strategies for regulating plasma cholesterol levels.
- This research has implications for preventing cardiovascular diseases like atherosclerosis, heart attacks, and strokes.
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