Y. Lange et al., ROLE OF THE PLASMA-MEMBRANE IN CHOLESTEROL ESTERIFICATION IN RAT HEPATOMA-CELLS, The Journal of biological chemistry, 268(19), 1993, pp. 13838-13843
The source of the cholesterol used for ester synthesis by cultured rat
hepatoma cells was examined. The activities synthesizing and esterify
ing cholesterol codistributed with RNA at a high buoyant density, pres
umably in the rough endoplasmic reticulum (RER). Cholesterol mass was
undetectable in the RER, and the transfer of cholesterol synthesized i
n the RER to the cell surface was more than 100 times greater than was
its esterification. Similarly, essentially all of the cholesterol lib
erated from ingested intracellular lipoproteins was recovered at the c
ell surface. The plasma membranes, which contained approximately 87% o
f cell cholesterol, provided >100 times more cholesterol for esterific
ation in the RER than did nascent cholesterol. The supply of cholester
ol was rate-limiting for esterification in cell homogenates. Prior oxi
dation of plasma membrane cholesterol in intact cells reduced the acyl
-CoA:chlosterol acyltransferase activity in isolates proportionately.
Finally, cholesterol in hepatoma plasma membranes was a far better sub
strate for in vitro esterification than was that in fibroblast plasma
membranes, red blood cell ghosts, or liposomes. We conclude that the l
evel of saturation of acyl-CoA:cholesterol acyltransferase, controlled
principally through the bidirectional movement of the substrate betwe
en plasma membranes and RER, plays a major role in the regulation of c
holesterol esterification.