Hepatic zonation of the formation and hydrolysis of cholesteryl esters in periportal and perivenous parenchymal cells

The periportal (PP) and perivenous (PV) zones of the liver acinus differ in enzyme complements and capacities for cholesterol and bile acid synthesis and other metabolic processes. The aim of this investigation was to determi ne the acinar distribution of the catalytic activity of the enzymes governi ng the formation and hydrolysis of cholesteryl esters using PP and PV hepat ocytes from normal or cholestyramine-fed rats. The hepatocyte subpopulation s were isolated by centrifugal elutriation, characterized according to the distribution pattern of a number of cell parameters and marker enzymes, and assayed for acyl-CoA:cholesterol acyltransferase (ACAT) and lysosomal, cyt osolic and microsomal cholesteryl ester hydrolase (CEH). In normally fed ra ts, no zonation was found in the activity of lysosomal CEH and ACAT, and th e activity of both cytosolic and microsomal CEH zonated toward the PV zone of the acinus. Concentrations of free and esterified cholesterol in homogen ates, cytosol, and microsomes of PP and PV cells were, however, similar. Ch olestyramine raised significantly the PV/PP ratio of ACAT because of an exc lusive PP reduction of activity and abolished the heterogeneity in microsom al CEH because of a greater inhibitory PV response, whereas the PV dominanc e of cytosolic CEH and the homogeneous distribution of lysosomal CEH were u naffected. These results demonstrated homogeneity within the liver acinus f or the enzymatic degradation of endocyted lipoprotein-derived cholesteryl e sters, a structural zonation of the cytosolic CEH and a dynamic zonation of ACAT and the microsomal CEH, with a PV dominance of the enzymatic capacity for the degradation of stored cholesteryl esters in normal livers.