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CARBOXYL ESTER LIPASE (CEL) IS A MAJOR ENZYME RESPONSIBLE FOR THE HYDROLYSIS OF CHOLESTERYL ESTERS IN THE SELECTIVE UPTAKE PATHWAY OF THE LIVER

by Chapman, Jamie M

Abstract (Summary)
Carboxyl ester lipase (CEL) is primarily a pancreatic enzyme that is also expressed in other tissues, including the mammary gland. Its expression and activity in the liver has been debated for many years. Our primary goal has been to link this enzyme's activity with the selective uptake pathway in the liver. Cholesterol esters that are accepted into cholesterol rich microdomains, termed caveolae, are preferentially shunted to the bile though a series of loosely defined endosomes and vesicles. These cholesterol esters must be hydrolyzed into free cholesterol before they are excreted into the bile. The site of this hydrolysis, and the enzyme responsible have not been identified. Our data indicate that CEL has activity in the liver, and that it is associated with caveolae. Mice deficient in this gene, have a mild increase (~20%) in cholesterol, both in the liver and in the serum, suggesting that cholesterol metabolism is altered in some way. Data also show that the hydrolysis of cholesterol esters at the level of caveolae is markedly decreased (> 2 fold) in the knockout animal, however, the liver's ability to take up cholesterol through this pathway does not appear to be altered. Excretion of cholesterol into the bile is increased two fold in the CEL knockout animals, and a statistically significant increase in phospholipid concentration and the bile acid, taurocholate, is also seen. Histological sectioning of CEL knockout liver shows a marked increase in the amount of neutral lipid in the liver. These data taken together indicate that CEL serves an important role in the metabolism of selectively internalized cholesterol esters. The data also show that this enzyme has its activity at the level of caveolae where the uptake of cholesterol esters through the selective pathway initiates.
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School:University of Cincinnati

School Location:USA - Ohio

Source Type:Master's Thesis

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Date of Publication:01/01/2000

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