Contribution of cholesterol 7alpha-hydroxylase to the regulation of lipoprotein metabolism.
Clinical studies have clearly established a relationship between bile acid synthesis and plasma LDL-cholesterol concentrations. Interruption of the enterohepatic circulation of bile acids leads to increased bile acid synthesis and a reduction in plasma LDL-cholesterol concentrations. New studies indicate that genetic variation in cholesterol 7alpha-hydroxylase activity accounts for a significant fraction of the inter-individual variation in plasma LDL-cholesterol concentrations in the general population, and a specific CYP7A1 allele associated with increased plasma LDL-cholesterol concentrations has been identified. Studies in which cholesterol 7alpha-hydroxylase was transiently overexpressed in hamsters and mice indicate that direct manipulation of cholesterol 7alpha-hydroxylase leads to changes in plasma LDL-cholesterol concentrations. Interestingly, targeted inactivation of the gene encoding cholesterol 7alpha-hydroxylase does not lead to increased plasma LDL-cholesterol concentrations in mice.
Cohen
J C
JC
The Centre for Human Nutrition and Department of Internal Medicine, University of Texas Southwestern Medical Centre, Dallas 75235-9052, USA. cohen@crcdec.swmed.edu
D000818:Animals; D002790:Cholesterol 7-alpha-Hydroxylase / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics
D008078:Cholesterol, LDL; D008074:Lipoproteins; D002790:Cholesterol 7-alpha-Hydroxylase