Cholesterol feedback: From Schoenheimer's bottle to Scap's MELADL

Research output: Contribution to journalReview article

303 Scopus citations

Abstract

Cholesterol biosynthesis is among the most intensely regulated processes in biology. Synthetic rates vary over hundreds of fold depending on the availability of an external source of cholesterol. Studies of this feedback regulatory process have a rich history. The field began 75 years ago when Rudolf Schoenheimer measured cholesterol balance in mice in a bottle. He found that cholesterol feeding led to decreased cholesterol synthesis, thereby introducing the general phenomenon by which end products of biosynthetic pathways inhibit their own synthesis. Recently, cholesterol feedback has been explained at a molecular level with the discovery of membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs), and an appreciation of the sterol-sensing role of their partner, an escort protein called Scap. The key element in Scap is a hexapeptide sequence designated MELADL (rhymes with bottle). Thus, over 75 years, Schoenheimer's bottle led to Scap's MELADL. In addition to their basic importance in membrane biology, these studies have implications for the regulation of plasma cholesterol levels and consequently for the development of atherosclerotic plaques, myocardial infarctions, and strokes. In this article we review the major milestones in the cholesterol feedback story.

Original languageEnglish (US)
Pages (from-to)S15-S27
JournalJournal of lipid research
Volume50
Issue numberSUPPL.
DOIs
StatePublished - Apr 1 2009

Keywords

  • Cholesterol biosynthesis
  • CopII-coated vesicles
  • HMG-CoA reductase
  • Historical aspects
  • Insig
  • LDL receptor
  • Membrane proteins
  • Oxysterols
  • SREBP pathway

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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