cDNA cloning of human milk bile-salt-stimulated lipase and evidence for its identity to pancreatic carboxylic ester hydrolase

Department of Molecular Biology, University of Göteborg, Sweden.
European Journal of Biochemistry (Impact Factor: 3.58). 10/1990; 192(2):543-50.
Source: PubMed


We have isolated and sequenced cDNA clones covering the entire coding sequence of human-milk bile-salt-stimulated lipase, as well as 996 nucleotides of the 3' end of the pancreatic enzyme carboxylic ester hydrolase. The deduced amino acid sequence of the lipase starts with a 23-residue leader peptide. The open reading frame continues with 722 amino acid residues. The sequence contains in the C-terminal part a proline-rich repeat, 16 repeats of 11 amino acid residues each. The mRNA was estimated to be approximately 2500 nucleotides from Northern blot and of similar size in mammary and pancreatic tissues. Data obtained indicate that the lipase and the carboxylesterase are identical and coded for by the same gene. The cDNA is 2428 bases long, which indicates that a near full-length copy of the transcript has been isolated. Comparisons with other enzymes show that the lipase is a new member of the supergene family of serine hydrolases. It is not only closely related (and in its N-terminal half virtually identical) to lysophospholipase from rat pancreas and cholesterol esterase from bovine pancreas, but also shows a high degree of similarity to several esterases, e.g. acetylcholine esterase. In contrast, no such similarity could be found to typical lipases.

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    • "Cholesterol esterase is produced by the pancreas and by the mammary glands in higher mammals, and if present in milk or yogurt could take part in the hydrolysis of esters (Hui & Howles, 2002). Nevertheless, it is unlikely that considerable concentrations of this enzyme would be present in milk or yogurt used in this study, since the commercial sterilization processing (UHT) of milk would inactivate this enzyme (Nilsson et al., 1990). "
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    ABSTRACT: Addition of lutein to dairy products is an alternative that widens the range of foods which could be lutein sources. However, bioaccessibility is an essential aspect to be considered during the development of products with added bioactive substances. We evaluated the in vitro bioaccessibility of lutein esters added to milk and yogurt with different fat contents, and determined the efficiency of enzymatic hydrolysis of the esters during digestion. Bioaccessibility of lutein and efficiency of hydrolysis were significantly lower in skimmed products than semi-skimmed and whole products, indicating that a minimal amount of fat is required to allow micellization and hydrolysis. The efficiency of ester hydrolysis ranged between 12 and 35%, which was attributed to pancreatic lipase. Whole and semi-skimmed samples were shown to be good vehicles for the addition of lutein, since presented bioaccessibility indices (38.3–47.5%) are similar to those found in natural food sources of xanthophylls.
    Full-text · Article · Nov 2014 · Food Research International
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    • "Human CEL is expressed predominantly in the lactating mammary gland and beta cells of the exocrine pancreas, where the enzyme contributes significantly to triglyceride, cholesterol ester and vitamin ester metabolism [5] [6] [7] [8] [9] [10]. CEL also promotes large chylomicron production in the intestine, and its presence in plasma supports interactions with cholesterol and oxidized lipoproteins [11] which may influence atherosclerosis progression [12]. "
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    ABSTRACT: Bile-salt activated carboxylic ester lipase (CEL) is a major triglyceride, cholesterol ester and vitamin ester hydrolytic enzyme contained within pancreatic and lactating mammary gland secretions. Bioinformatic methods were used to predict the amino acid sequences, secondary and tertiary structures and gene locations for CEL genes, and encoded proteins using data from several vertebrate genome projects. A proline-rich and O-glycosylated 11-amino acid C-terminal repeat sequence (VNTR) previously reported for human and other higher primate CEL proteins was also observed for other eutherian mammalian CEL sequences examined. In contrast, opossum CEL contained a single C-terminal copy of this sequence whereas CEL proteins from platypus, chicken, lizard, frog and several fish species lacked the VNTR sequence. Vertebrate CEL genes contained 11 coding exons. Evidence is presented for tandem duplicated CEL genes for the zebrafish genome. Vertebrate CEL protein subunits shared 53-97% sequence identities; demonstrated sequence alignments and identities for key CEL amino acid residues; and conservation of predicted secondary and tertiary structures with those previously reported for human CEL. Phylogenetic analyses demonstrated the relationships and potential evolutionary origins of the vertebrate CEL family of genes which were related to a nematode carboxylesterase (CES) gene and five mammalian CES gene families.
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    • "Besides the pancreas, this enzyme has also been identified in other organs, where it plays different physiological roles. The lactating mammary gland synthesizes and secretes an enzyme named human-milk bilesalt–stimulated lipase, which is identical to pancreatic CEL (Wang 1988; Nilsson et al. 1990; Christie et al. 1991) and, after specific activation by primary bile salts, contributes to the breast-fed infant's endogenous capacity for intestinal fat digestion (Bernbäck et al. 1990). In addition, an enzyme identical to CEL has been found in endothelial cells lining the wall of vessels, where it is thought to be involved in mechanisms leading to the accumulation of atherogenic lipoproteins (Brodt-Eppley et al. 1995; Li and Hui 1998). "
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    ABSTRACT: Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells.
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