|Van Bennekum, Ariette|
Submitted to: Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/25/1998
Publication Date: N/A
Citation: N/A Interpretive Summary: This work used genetic engineering techniques to show that a particular enzyme (called carboxyl ester lipase or CEL) secreted by the pancreas and liver was not involved in the metabolism of dietary vitamin A in the liver. Since this enzyme has long been studied as a retinyl ester hydrolase in vitro this work is significant in that it rules out a physiological role for the enzyme in vitamin A metabolism in the liver. This work contributes to an understanding of the whole body economy of this essential vitamin. The work will be useful to scientists studying the metabolism and function of vitamin A and may ultimately aid in our understanding of how the vitamin is stored in and released from the liver.
Technical Abstract: In order to study the role of carboxyl ester lipase (CEL) in hepatic retinoid (vitamin A) metabolism, we investigated uptake and hydrolysis of chylomicron (CM)-retinyl esters by rat hepatoma (McArdle-RH7777) cells stably transfected with a rat CEL cDNA. We also studied tissue uptake of CM-retinyl ester in CEL-deficient mice generated by targeted disruption of the CEL gene. CEL transfected cells secreted active enzyme into the medium. However, both control and CEL-transfected cells accumulated exogenously added CM- or CM remnant (CMR)-derived retinyl ester in equal amounts. Serum clearance of intravenously-injected CM-retinyl ester and cholesteryl ester were not different between wild type and CEL-deficient mice. Also, the uptake of the two compounds by the liver and other tissues did not diff. These data indicate that the lack of CEL expression does not affect the uptake of dietary CM-retinyl ester in the liver or other tissues. Moreover, the percentage of retinol formed in the liver after CM-retinyl ester uptake, the level of retinol and retinol-binding protein (RBP) in serum, and retinoid levels in various tissues did not differ, indicating that CEL deficiency does not affect hepatic retinoid metabolism. Surprisingly, in both pancreas and liver of wild type, heterozygous and homozygous CEL-deficient mice the level of bile salt-dependent retinyl ester hydrolase (REH) activity was similar. This indicates that in the mouse pancreas and liver an REH enzyme activity, active in the presence of bile salt and distinct from CEL, is present.