Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 (RE) by rat hepatoma (McArdle-RH7777) cells stably transfected with a rat CEL cDNA. We also studied tissue uptake of CM-RE 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-RE or CM remnant (CMR)-derived RE in equal amounts. Serum clearance of intravenously injected CM-RE 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 differ. These data indicate that the lack of CEL expression does not affect the uptake of dietary CM-RE by the liver or other tissues. Moreover, the percentage of retinol formed in the liver after CM-RE uptake, the levels of retinol and retinol-binding protein in serum, and retinoid levels in various tissues did not differ, indicating that CEL deficiency does not affect hepatic retinoid metabolism and retinoid distribution throughout the body. Surprisingly, in both pancreas and liver of wild-type, heterozygous, and homozygous CEL-deficient mice, the levels of bile salt-dependent retinyl ester hydrolase (REH) activity were 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, compatible with the results from our accompanying paper that the intestinal processing and absorption of RE were unimpaired in CEL-deficient mice.
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PMID:Carboxyl ester lipase overexpression in rat hepatoma cells and CEL deficiency in mice have no impact on hepatic uptake or metabolism of chylomicron-retinyl ester. 1019 31

Retinoids function through conformational alterations of ligand-dependent nuclear transcription factors, the retinoic acid receptors, and retinoid X receptors. 9-cis-Retinoic acid is a known biological ligand for retinoid X receptors, but its synthesis pathway in vivo is largely unknown. Recently, we identified a cis-retinol dehydrogenase (cRDH) that oxidizes 9-cis-retinol to 9-cis-retinal. Since both the expression of cRDH mRNA and its substrate are found in liver, we studied 9-cis-retinol metabolism and 9-cis-retinoic acid biosynthesis in two hepatic-derived cell types, Hep G2 hepatoma cells and HSC-T6 stellate cells. Both cell lines accumulate similar amounts of 9-cis-retinol provided in the medium. However, Hep G2 cells preferentially incorporate all-trans-retinol when equimolar concentrations of all-trans- and 9-cis-retinol were provided. In contrast, HSC-T6 cells did not exhibit a preference between all-trans- and 9-cis-retinol under the same conditions. Esterification of 9-cis-retinol occurred in both cell types, likely by acyl-CoA:retinol acyltransferase and lecithin:retinol acyltransferase. In vitro enzyme assays demonstrated that both cell types can hydrolyze 9-cis-retinyl esters via retinyl ester hydrolase(s). In Hep G2 cells, 9-cis-retinoic acid synthesis was strongly inhibited by high concentrations of 9-cis-retinol, which may explain the low levels of 9-cis-retinol in liver of mice. Cell homogenates of Hep G2 can convert all-trans-retinol to 9-cis-retinal, suggesting that the free form of all-trans-retinol may be used as a source for 9-cis-retinol and, thus, 9-cis-retinoic acid synthesis. Our studies provide the basis for identification of additional pathways for the generation of 9-cis-retinoic acid in specialized tissues.
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PMID:9-cis-retinoids: biosynthesis of 9-cis-retinoic acid. 1089 Oct 90