Carboxyl ester lipase: structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis.
Carboxyl ester lipase (CEL), previously named cholesterol esterase or bile salt-stimulated (or dependent) lipase, is a lipolytic enzyme capable of hydrolyzing cholesteryl esters, tri-, di-, and mono-acylglycerols, phospholipids, lysophospholipids, and ceramide. The active site catalytic triad of serine-histidine-aspartate is centrally located within the enzyme structure and is partially covered by a surface loop. The carboxyl terminus of the protein regulates enzymatic activity by forming hydrogen bonds with the surface loop to partially shield the active site. Bile salt binding to the loop domain frees the active site for accessibility by water-insoluble substrates. CEL is synthesized primarily in the pancreas and lactating mammary gland, but the enzyme is also expressed in liver, macrophages, and in the vessel wall. In the gastrointestinal tract, CEL serves as a compensatory protein to other lipolytic enzymes for complete digestion and absorption of lipid nutrients. Importantly, CEL also participates in chylomicron assembly and secretion, in a mechanism mediated through its ceramide hydrolytic activity. Cell culture studies suggest a role for CEL in lipoprotein metabolism and oxidized LDL-induced atherosclerosis. Thus, this enzyme, which has a wide substrate reactivity and diffuse anatomic distribution, may have multiple functions in lipid and lipoprotein metabolism, and atherosclerosis.
Hui
David Y
DY
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA. huidy@email.uc.edu
Howles
Philip N
PN
D001161:Arteriosclerosis / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D001665:Binding Sites; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002914:Chylomicrons / Q000378:metabolism; D018360:Crystallography, X-Ray; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D013329:Structure-Activity Relationship; D014815:Vitamins / Q000378:metabolism
D001647:Bile Acids and Salts; D002914:Chylomicrons; D008074:Lipoproteins; D014815:Vitamins; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase