Dietary cholesterol, membrane cholesterol and cholesterol synthesis.
After describing the main steps of cholesterol biosynthesis the author recalls that the cholesterogenesis rate is feedback-inhibited by dietary cholesterol and examines the various processes of modulation. Hydroxy-3-methylglutaryl (HMG) CoA reductase, the key rate-limiting enzyme, is a 97 kDa endoplasmic reticulum glycoprotein, anchored 7-fold in this membrane. The N-terminal membrane-bound domain plays a fundamental role in the modulation of reductase activity. This modulation is essentially mediated by decreased gene transcription and enhanced degradation of the protein. The possible modulation by a bicyclic cascade system involving phosphorylation (inactivation) and dephosphorylation (activation) of reductase does not seem to play an essential role in vivo. Finally, recent data show that the lipid composition (C/P molar ratio) of some reticular membranes (fibroblasts, for example) can strongly modulate the activity of this ubiquitous enzyme.
Lutton
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Laboratoire de Physiologie de la Nutrition, Université Paris Sud, Orsay, France.
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D005246:Feedback; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008563:Membrane Lipids / Q000096:biosynthesis*; D010766:Phosphorylation
D002791:Cholesterol, Dietary; D008563:Membrane Lipids; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases