title: Regulation of hepatic cholesterol metabolism in man.
abstract: The liver is a key element in regulating the amount of low density lipoprotein (LDL) cholesterol in plasma. The interference of cholestyramine treatment in the enterohepatic circulation of bile acids stimulates the activity of the rate limiting enzymatic step in bile acid biosynthesis (cholesterol 7 alpha-hydroxylase). This increases demand for cholesterol which is met by enhanced cholesterol biosynthesis (through the enzyme 3-hydroxy-3-methylglutaryl coenzyme A [HMG CoA] reductase) and by an increased expression of LDL receptors. Inhibition of HMG CoA reductase activity by treatment with specific inhibitors such as pravastatin enhances LDL receptor binding activity. Combination of the two treatments results in a significant stimulation of LDL receptor expression and a drastic reduction in the concentration of plasma LDL cholesterol. Thus, selective interference with bile acid enterohepatic circulation and cholesterol biosynthesis may be utilised to regulate plasma lipoprotein metabolism.
authors.affiliation: Department of Medicine, Huddinge University Hospital, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Angelin
mesh_terms: D002769:Cholelithiasis / Q000188:drug therapy / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D002792:Cholestyramine Resin / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009281:Naphthalenes / Q000627:therapeutic use; D017035:Pravastatin; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009281:Naphthalenes; D011973:Receptors, LDL; D002792:Cholestyramine Resin; D002784:Cholesterol; D017035:Pravastatin