PHRM 211 Lecture Notes - Lecture 3: Combined Hyperlipidemia, Lipoprotein Lipase Deficiency, Familial Hypercholesterolemia
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Free cholesterol : sits on outer membrane; hydroxyl group points out to surface (hydrophilic) Cmr : reduced tg relative to cm, more cholesterol. Vldl : tg rich (but less than cm), dense. Compare 4 ammonium of cholestyramine versus 2 & 3 amines of colestipol. Bind to bile acids primarily through ionic interactions in git. Greatly increase fecal elimination of glycocholic & taurocholic acids. With increased conversion of cholesterol to bile acids (i. e. decrease in hepatic cholesterol), compensatory mechanisms to increase cholesterol levels occur: Transient increase in vldl (persistent rise for hypertriglyceridemia patients) Microsomal enzyme (anchored to er) found mainly in the liver. Catalyzes stereospecific conversion of (s)-hmg to (r)-mevalonic acid rate-limiting step in cholesterol biosynthesis. Reduction involves transfer of 4 electron equivalents (2h-) provided by 2 nadph. Transition state is stabilized by a network of active site residues. Discovered as metabolites isolated from penicillin, monascus and aspergillus fungi. Found to be competitive inhibitors of hmg-coa reductase.
