Inhibitors of sterol synthesis. Oleate ester of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one as a substrate for pancreatic cholesterol esterase.
5 alpha-Cholest-8(14)-en-3 beta-yl-15-one oleate (15-ketosteryl oleate), the oleate ester of a compound with the capacity to lower serum cholesterol, was effectively hydrolyzed by partially purified porcine pancreatic cholesterol esterase with an apparent Km of 0.28 +/- 0.01 mM and a Vmax of 0.62 +/- 0.01 mumol/min per mg protein compared to an apparent Km of 0.19 +/- 0.02 mM and a Vmax of 0.37 +/- 0.02 mumol/min per mg protein for cholesteryl oleate. The 15-ketosteryl oleate was also hydrolyzed by highly purified rat pancreatic cholesterol esterase with an apparent Km of 0.20 +/- 0.01 mM and a Vmax of 86.7 +/- 3.0 mumol/min per mg protein compared to an apparent Km of 0.43 +/- 0.01 mM and a Vmax of 119.8 +/- 2.6 mumol/min per mg protein for cholesteryl oleate. 15-Ketosteryl oleate is, therefore, a good substrate for pancreatic cholesterol esterase from either source. The 15-ketosterol is a weak competitive inhibitor of partially purified porcine pancreatic cholesterol esterase when cholesteryl oleate is the substrate.
Stephens
T W
TW
Department of Biochemistry, Rice University, Houston, TX.
Schroepfer
G J
GJ
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002782:Cholestenes / Q000378:metabolism*; D002783:Cholestenones / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D010179:Pancreas / Q000201:enzymology*; D051381:Rats; D002787:Sterol Esterase / Q000378:metabolism*; D013261:Sterols / Q000096:biosynthesis*; D013552:Swine
D002782:Cholestenes; D002783:Cholestenones; D002788:Cholesterol Esters; D013261:Sterols; C058054:cholest-8(14)-en-3-yl-15-one oleate; C014409:cholesteryl oleate; C015073:cholest-8(14)-en-3-ol-15-one; D002265:Carboxylic Ester Hydrolases; D002787:Sterol Esterase