Hepatic uptake and metabolism of chylomicron retinyl esters: probable role of plasma membrane/endosomal retinyl ester hydrolases

E H Harrison,M Z Gad,A C Ross

doi:10.1016/s0022-2275(20)39737-6

Abstract

Previous studies have indicated the presence of both neutral and acid, bile salt-independent retinyl ester hydrolases associated with plasma membrane and endosome fractions of rat liver homogenates. In the present studies, chylomicrons containing tritium-labeled retinyl esters were injected intravenously into rats in order to study the initial metabolism of retinyl esters during and after uptake into the liver. At various times after chylomicron injection, plasma was obtained and the liver was homogenized and subjected to analytical subcellular fractionation. Labeled retinyl esters were rapidly cleared from plasma (half-time approximately 10 min) and appeared in the liver. Within the liver, label first appeared in plasma membrane/endosomal fractions that were also enriched in both neutral and acid, bile salt-independent retinyl ester hydrolase activities. At no time were the labeled esters significantly associated with fractions enriched in lysosomes. Rather, it appeared that the labeled esters were hydrolyzed and/or transferred to fractions enriched in endoplasmic reticulum. These studies demonstrate the co-localization of newly delivered retinyl esters and bile salt-independent retinyl ester hydrolase enzyme activities and thus, suggest a probable role for these enzymes in the initial hepatic metabolism of chylomicron retinyl esters. This conclusion was further supported by the observation that plasma membrane/endosomal fractions were active in catalyzing the hydrolysis of chylomicron remnant retinyl esters in vitro.

Highlights

Previous studies have indicated the presence of both neutral and acid, bile salt-independentretinyl ester hydrolases associated with plasma membrane and endosome fractions of rat liver homogenates
Less than 15% of the injected chylomicrons were initially sequestered at sites other than the liver. After this initial hepatic uptake, which reached a maximum near 30 min, 3H in liver thereafter steadily declined; between 30 min and 2 h about 30% of the injected dose was lost from the liver and could not be accounted for by reappearance in the lOOr
In experiments in which 1251-labeled asialofetuin was injected simultaneously with labeled chylomicrons, we observed that the asialoglycoprotein was cleared from the plasma and taken up by the liver more rapidly than the labeledchylomicrons.Our data for asialofetuinwere nearly identical to those reported previously for this ligand, known to be internalized by receptor-mediated endocytosis after binding to the asialoglycoproteinreceptor on hepatocyte plasma membranes [24,25].the asialoglycoprotein was cleared from the plasma with a half-timeof less than 5 min

Summary

Introduction

Previous studies have indicated the presence of both neutral and acid, bile salt-independentretinyl ester hydrolases associated with plasma membrane and endosome fractions of rat liver homogenates. Label first appeared in plasma membrane/endosomal fractions that were enriched in both neutral and acid, bile salt-independentretinyl ester hydrolase activities. M These studies demonstrate the co-localization of newly delivered retinyl esters and bile salt-independent retinyl ester hydrolase enzyme activities and suggest a probable role for these enzymes in the initial hepatic metabe lism of chylomicron retinyl esters. This conclusion was further supported by the observation that plasma membrane/endosomal fractions were active in catalyzing the hydrolysis of chylomicron remnant retinyl esters in vitro.-Harrison, E.

Methods

Results

Conclusion