HEPATIC-UPTAKE AND METABOLISM OF CHYLOMICRON RETINYL ESTERS - PROBABLE ROLE OF PLASMA-MEMBRANE ENDOSOMAL RETINYL ESTER HYDROLASES

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 pres ent studies, chylomicrons containing tritium-labeled retinyl esters we re injected intravenously into rats in order to study the initial meta bolism of retinyl esters during and after uptake into the liver. At va rious times after chylomicron injection, plasma was obtained and the l iver was homogenized and subjected to analytical subcellular fractiona tion. Labeled retinyl esters were rapidly cleared from plasma (half-ti me approximate to 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 signif icantly associated with fractions enriched in lysosomes. Rather, it ap peared that the labeled esters were hydrolyzed and/or transferred to f ractions enriched in endoplasmic reticulum. These studies demonstrate the co-localization of newly delivered retinyl esters and bile salt-in dependent 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 i n catalyzing the hydrolysis of chylomicron remnant retinyl esters in v itro.