Bile salt-dependent, neutral cholesteryl ester hydrolase of rat liver: possible relationship with pancreatic cholesteryl ester hydrolase

Abstract

Homogenates of the livers of outbred, Sprague-Dawley rats contain a neutral cholesteryl ester hydrolase activity that requires millimolar concentrations of bile salts for maximal activity. Previous studies showed that this activity had the unusual property of being highly variable among individual rats. The present studies were conducted to define further the nature of this enzymic activity and to explore the possible basis for the variability. Individual liver homogenates from inbred Fisher-344 rats showed the same range and magnitude of activity as outbred rats, suggesting that genetic heterogeneity was not a factor in determining the enzyme activity. Tissue distribution studies showed the presence of a very similar enzyme activity in serum, bile and intestinal homogenates, with the specific activity in intestine being 25-500-times greater than that in liver. Moreover, the enzymic properties of the activity in serum, liver and intestine were identical to those of purified rat pancreatic cholesteryl ester hydrolase (EC 3.1.1.13). Monospecific, anti-pancreatic hydrolase IgG specifically and completely inhibited the cholesteryl ester hydrolase activity in rat serum, intestine and liver. The results raise the possibility that the neutral, bile salt-dependent cholesteryl ester hydrolase activity of rat liver homogenates may be due to the uptake of enzyme originating in the pancreas. This, in turn, may explain the dramatic variation in activity observed among individual rat livers.