The participation of sterol carrier protein2 in the conversion of cholesterol to cholesterol ester by rat liver microsomes.
The purification of sterol carrier protein2 (SCP2), purified 1500-fold to homogeneity from the 303,000 x g supernatant (S303) of rat liver, has recently been described (Noland, B. J., Arebalo, R. E., Hansbury, E., and Scallen T. J. (1980) J. Biol. Chem, 255, 4282-4289). Since SCP2 is required for the synthesis of cholesterol by microsomal membranes, it was decided to test the hypothesis that SCP2 might also participate in enzymatic reactions which utilize cholesterol as a substrate. The reaction studied in the present investigation was the conversion of cholesterol to cholesterol ester (acyl-CoA cholesterol acyltransferase) by rat liver microsomes. The results show that when exogenously added [4-14C]cholesterol is the substrate, SCP2 produces a striking increase in cholesterol ester biosynthesis by rat liver microsomes. Although the effect of SCP2 was most clearly seen with exogenously added cholesterol, it was also demonstrated when [1-14C]oleoyl-CoA was the labeled substrate and the incorporation of labeled oleate into cholesterol ester was determined. Although it was demonstrated that microsomes could bind large amounts of cholesterol in the absence of SCP2, the bound cholesterol was ineffective as a substrate for microsomal acyl-CoA cholesterol acyltransferase. However, the microsomally bound cholesterol became an effective substrate for the enzyme upon the addition of SCP2. The results demonstrate that SCP2 participates in the utilization of cholesterol via the microsomal conversion of cholesterol to cholesterol ester. We also conclude that SCP2 may participate in the intracellular transport of cholesterol, in particular, the delivery of either exogenous (dietary) cholesterol or endogenous cholesterol to acyl-CoA cholesterol acyltransferase in the endoplasmic reticulum.
D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000096:biosynthesis*; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010940:Plant Proteins; D051381:Rats; D013261:Sterols / Q000302:isolation & purification / Q000378:metabolism*
D002352:Carrier Proteins; D002788:Cholesterol Esters; D010940:Plant Proteins; D013261:Sterols; C072087:sterol carrier proteins; D002784:Cholesterol