Cholesterol esterase lipase

R. J. Kazlauskas, A. N. E. Weissfloch, A. T. Rappaport, L. A. Cuccia, A Rule to Predict Which Enantiomer of a Secondary Alcohol Reacts Faster in Reactions Catalyzed by Cholesterol Esterase, Lipase from Pseudomonas cepacia, and Lipase From Candida rugosa, J. Org. Chem. 1991, 56, 2655 - 2665. 

R.. Kazlauskas, A.N.E. Weissfloch, A. Rappaport, L. Cuccia, A rule to predict which enantiomer of a secondary alcohol reacts faster in reactions catalyzed by cholesterol esterase, lipase from Pseudomonas cepacia, and lipase from Candida rugosa,. Oig. Chem. 56 (1991) 2656-2665. 

R. M. Stroud, Structure of Bovine Pancreatic Cholesterol Esterase at 1.6 A Novel Structural Features Involved in Lipase Activation , Biochemistry 1998, 37, 5107-5117. 

Fig. 7.4. A simple topographical model showing the absolute configuration of the acetates reacting faster with cholesterol esterase and lipase (modified from [19]). S = smaller group ...

Figure 8. Enzymatic preparation of (S)- and (R)-furyl methyl carbinol. TADH, Thermoanaerobium brokii alcohol dehydrogenase (NADPH was regenerated by glucose/glucose dehydrogenase from Bacillus cereus obtained from Amano.) CCL, lipase from Candida cvlindraceae ChE, cholesterol esterase from Pseudomonas.

In a like manner, a co-polymer of styrene and acryloxysuccinimide with a 10 to 1 ratio was prepared. Enzymes immobilized on this type of polymer had different physical properties. They are soluble in organic solvents such as dioxane and DMF, but insoluble in aqueous solutions. Lipases and cholesterol esterase immobilized on this type of polymer are very stable and active in several organic solvents, and have been used in several enantioselective transformations. The protocols for the immobilization are depicted in Figure 13. 

A rule, similar to Prelog s rule, has been proposed for the enzyme-mediated hydrolysis of the esters of secondary alcohols. Esters of the enantiomers 31 usually react faster. This rule correctly predicted the configuration of 14 out of 15 substrates when cholesterol esterase was used, 63 out of 64 substrates with a lipase from Pseudomonas cepacia, and of 51 out of 55 cyclic substrates using a lipase from Candida rugosa24°. 

TIL Thermomyces lanuginosus lipase, RdL Rhizopus delemar lipase, RnL Rhizopus niveus lipase, MmE Mucor miehei esterase, PsL Pseudomonas sp. lipase, MmL Mucor miehei lipase, RoL Rhizopus orvzae lipase, CaLA Candida antarctica lipase A, CaLB Candida antarctica lipase B, PLE Pig liver esterase, EP Enteropeptidase, PKA Porcine kidney acylase, CE Cholesterol esterase Figure 8.1 (S)-Selective enzyme hits from hydrolase screening. ... 

In the duodenum, dietary lipids are degraded by pancreatic enzymes triacylglycerol by pancreatic lipase, phospholipids by phospholipase A2 and lysophospholipase, and cholesteryl esters by cholesterol esterase. Enzyme release from the pancreas is controlled by cholecystokinin, produced by cells in the intestinal mucosa. 

Howies, P.N., Carter, C.P., and Hui, D.Y. 1996. Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice. J. Biol. Chem. 271, 7196-7202. 

The search for intestinal cholesterol transporters extended for many years, beginning with a debate about whether or not it was even a protein-facilitated process (4, 5). The pancreatic enzyme carboxyl ester lipase (CEL, also called cholesterol esterase) was believed to be important to this process (6,7) and several companies devoted considerable resources to the development and testing of compounds to inhibit CEL, with mixed results (8-10). These efforts were abandoned in the mid-1990s, however, after studies with gene-knockout mice demonstrated that the enzyme was important only for absorption of cholesteryl ester (11, 12), which is a minor component of dietary cholesterol and is present at very low levels in bile. Interestingly, CEL is also found in liver where it has been shown to affect HDL metabolism (13). Thus, it may ultimately play an important role in cholesterol metabolism and may yet prove to be a useful drug target for CVD treatment (Camarota and Howies, unpublished). 

While it was previously thought that the lipase of pancreatic origin, the classical lipase, was responsible for the digestion of most dietary fat, it has become clear in recent years that lipolysis in the gastrointestinal rat is a result of the conceited action of four different types of lipases gastric Kpase, classical pancreatic lipase, pancreatic carboxyl ester lipase (identical to cholesterol esterase), and phos-... 

The esterases are involved in the hydrolysis of ester linkages of various types. The products formed are acid and alcohol. These enzymes may hydrolyze triglycerides and include several lipases for instance, phospholipids are hydrolyzed by phospholipases, and cholesterol esters are hydrolyzed by cholesterol esterase. The carboxylesterases are enzymes that hydrolyze triglycerides such as tributyrin. They can be distinguished from lipases because they hydrolyze soluble substrates, whereas lipases only act at the water-lipid interfaces of emulsions. Therefore, any condition that results in increased surface area of the water-lipid interface will increase the activity of the enzyme. This is the reason that lipase activity is much greater in homogenized (not pasteurized) milk than in the non-homogenized product. Most of the lipolytic enzymes are specific for either the acid or the alcohol moiety of the substrate, and, in the case of esters of polyhydric alcohols, there may also be a positional specificity. 

Cholesterol esterase, 10000 U/l lipase 20000 U/l and phospholipase A2 (from Naja naja venom 10000 U/l Sigma Chemicals, U.K.). /J-Eleostearic acid (internal standard [18 3(9,11,13-cw)]) from Alltech Associates, U.K. 

Enzymes that hydrolyze lysophospholipids are found in nearly all tissues and organisms. They seem to be non-specific esterases of the serine-histidine type (25) and hardly deserve the name lysophospholipase because they also hydrolyze esters other than phospholipids. They should probably be considered together with such enzymes as cholesterol esterases and monoglyceride lipases as amphiphilic carboxyl ester hydrolases. These non-specific esterases have a preference for amphiphilic (hydrophilic-lipophilic) substrates. Such an enzyme may perhaps hydrolyze lysophospholipis, monoglycerides, diglycerides, and cholesterol esters. 

Lipolysis starts at the water/emulsion interphase. The major enzymes involved are pancreatic lipase, pancreatic phospholipase A2, and pancreatic cholesterol esterase, the latter also named bile-salt-dependent lipase. 

Bile Salt-Activated Lipase (Cholesterol Esterase)... 

The ll-palm-A -THC can be hydrolyzed to II-OH-A -thc by cholesterol esterase and triacylglycerol lipase but not by phospholipase A, acetylesterase or phosphotransacetylase (16). An attempt to modify the retention of fatty acid-conjugated DDT metabolites was carried out by injecting the DDT-treated rats with sodium salt of various bile acids, heparin or lecithin of which all were known to affect the esterification or ester hydrolysis by the cholesterol esterase system. The results Indicated a significant decrease in the retention of the conjugated DDT metabolites in the rat liver and spleen (17). 

Pancreatic carboxylester lipase, secreted by the pancreas as an active enzyme without proteolytic activation, displays broad substrate specificity and has therefore received many names in the literature carboxylesterase, bile salt-stimulated (or activated or dependent) lipase (due to its absolute requirement for bile salts to hydrolyze insoluble substrates), carboxylester lipase or hydrolase, cholesterol esterase, lysophospholipase, nonspecific lipase, and monoglyceride lipase. The IUPAC classification of the enzyme has been either EC.3.1.1.1 (carboxylester hydrolase) or EC.3.1.1.13 (cholesterolester hydrolase) (Table 2). 

Figure 9 The pancreolauryl test allows an indirect assessing of exocrine pancreatic function. Orally administered fluorescein dilaurate is hydrolyzed by carboxylester lipase (identical to cholesterol esterase) liberating lauric acid and free, water-soluble fluorescein. The latter is readily absorbed in the small intestine, partly conjugated in the liver, and excreted in urine mainly as fluorescein glucuronide. By measuring the concentration of fluorescein in the urine over a period of, for instance, 10 hours, the total quantity of this dye is determined. (From Ref. 52.)...

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