Esterase cholesterol

Page 1093 (Figure 26 9c) is adapted from crystallographic coordinates deposited with the Protein Data Bank PDB ID ICLE Ghosh D Wawrzak Z Pletnev V Z Li N Kaiser R Pangbom W Jornvall H Erman M Duax W L Structure of Un complexed and Linoleate Bound Candida Cholesterol Esterase To be published... 

Free cholesterol can also be determined, if cholesterol esterase is omitted. 

Parameter Cholesterol oxidase (CO) Cholesterol esterase (CE) Glucose oxidase (GOD) Peroxidase (POD)... 

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

Cholesterol Cholesterol esterase and cholesterol oxidase Medical care... 

A.L. Crumbliss, J.Z. Stonehuerner, R.W. Henkens, J. Zhao, and J.P. O Daly, A carrageenan hydrogel stabilized colloidal gold multi-enzyme biosensor electrode utilizing immobilized horseradish peroxidase and cholesterol oxidase/cholesterol esterase to detect cholesterol in serum and whole blood. Biosens. Bioelectron. 8, 331-337 (1993). 

Sterol esterase Steryl-ester acylhydrolase, cholesterol esterase Steryl esters... 

The overall metabolism of vitamin A in the body is regulated by esterases. Dietary retinyl esters are hydrolyzed enzymatically in the intestinal lumen, and free retinol enters the enterocyte, where it is re-esterified. The resulting esters are then packed into chylomicrons delivered via the lymphatic system to the liver, where they are again hydrolyzed and re-esterified for storage. Prior to mobilization from the liver, the retinyl esters are hydrolyzed, and free retinol is complexed with the retinol-binding protein for secretion from the liver [101]. Different esterases are involved in this sequence. Hydrolysis of dietary retinyl esters in the lumen is catalyzed by pancreatic sterol esterase (steryl-ester acylhydrolase, cholesterol esterase, EC 3.1.1.13) [102], A bile salt independent retinyl-palmitate esterase (EC 3.1.1.21) located in the liver cell plasma hydrolyzes retinyl esters delivered to the liver by chylomicrons. Another neutral retinyl ester hydrolase has been found in the nuclear and cytosolic fractions of liver homogenates. This enzyme is stimulated by bile salts and has properties nearly identical to those observed for... 

The intestinal absorption of dietary cholesterol esters occurs only after hydrolysis by sterol esterase steryl-ester acylhydrolase (cholesterol esterase, EC 3.1.1.13) in the presence of taurocholate [113][114], This enzyme is synthesized and secreted by the pancreas. The free cholesterol so produced then diffuses through the lumen to the plasma membrane of the intestinal epithelial cells, where it is re-esterified. The resulting cholesterol esters are then transported into the intestinal lymph [115]. The mechanism of cholesterol reesterification remained unclear until it was shown that cholesterol esterase EC 3.1.1.13 has both bile-salt-independent and bile-salt-dependent cholesterol ester synthetic activities, and that it may catalyze the net synthesis of cholesterol esters under physiological conditions [116-118], It seems that cholesterol esterase can switch between hydrolytic and synthetic activities, controlled by the bile salt and/or proton concentration in the enzyme s microenvironment. Cholesterol esterase is also found in other tissues, e.g., in the liver and testis [119][120], The enzyme is able to catalyze the hydrolysis of acylglycerols and phospholipids at the micellar interface, but also to act as a cholesterol transfer protein in phospholipid vesicles independently of esterase activity [121],... 

J. Hyun, C. R. Treadwell, G. V. Vahouny, Pancreatic Juice Cholesterol Esterase. Studies on Molecular Weigth and Bile Salt-Induced Polymerization , Arch. Biochem. Bio-phys. 1972, 752, 233-242. 

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. 

L. L. Gallo, S. B. Clark, S. Myers, G. V. Vahouny, Cholesterol Absorption in Rat Intestine Role of Cholesterol Esterase and Acyl Coenzyme A Cholesterol Acyltransferase , J. Lipid Res. 1984, 25, 604-612. 

E. M. Kyger, D. J. S. Riley, C. A. Spilburg, L. G. Lange, Pancreatic Cholesterol Esterases. 3. Kinetic Characterization of Cholesterol Ester Resynthesis by Pancreatic Cholesterol Esterases , Biochemistry 1990, 29, 3853-3858. 

There are a few reported cases of esterases that catalyze not only hydrolysis but also the reverse reaction of ester formation, in analogy with the global reaction described for serine peptidases (Fig. 3.4). Thus, cholesterol esterase can catalyze the esterification of oleic acid with cholesterol and, more importantly in our context, that of fatty acids with haloethanols [54], Esterification and transesterification reactions are also mediated by carboxyleste-rases, as discussed in greater detail in Sect. 7.4. 

J. A. Doom, T. T. Talley, C. M. Thompson, R. J. Richardson, Probing the Active Site of Butyrylchohnesterase and Cholesterol Esterase with Isomalathion Conserved Stereoselective Inactivation of Serine Hydrolases Structurally Related to Acetylchohnesterase , Chem. Res. Toxicol. 2001, 14, 807-813. 

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 ...

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. 

L. D. Sutton, J. S. Stout, D. M. Quinn, Dependence of Transition-State Structure on Acyl Chain Length for Cholesterol Esterase Catalyzed Hydrolysis of Lipid p-Nitrophen-yl Esters ,./. Am. Chem. Soc. 1990, 112, 8398-8403. 

All of the above examples are acetates of active alcohols. Here, we also mention the acetate of a phenol, namely the provitamin a-tocopheryl acetate, whose natural enantiomer of absolute configuration (2R,47 ,87 ) is shown as 8.73. a-Tocopheryl acetate is a substrate of cholesterol esterase (EC 3.1.1.13), and was hydrolyzed in rats faster than its (2S,47 ,87 )-epimer. In vitro experiments required a-tocopheryl acetate to be dispersed as a micellar pseudosolution, and the nature of the bile salt used to prepare micelles had a profound effect on the substrate stereoselectivity of the reaction [95] [96], Only when the micelle composition approximated that of the gastrointestinal tract did the in vitro substrate stereoselectivity resemble that seen in vivo. 

A. N. J. Moore, P. J. Dutton, H. A. Zahalka, G. W. Burton, K. U. Ingold, Bile Salt Modulated Stereoselection in the Cholesterol Esterase-Catalyzed Hydrolysis of alpha-To-copheryl Acetates ,./. Am. Chem. Soc. 1995, 117, 5677-5686. 

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. 

This enzyme [EC 3.1.1.13] (also known as cholesterol esterase, sterol esterase, cholesterol ester synthase, and triterpenol esterase) catalyzes the hydrolysis of a steryl ester to produce a sterol and a fatty acid anion. This class represents a group of enzymes exhibiting broad specificity. They act on esters of sterols and long-chain fatty acids, and may also bring about the esterification of sterols. These enzymes are typically activated by bile salts. See also Esterases D. P. Hajjar (1994) Adv. Enzymol. 69, 45. 

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°. 

The resolution of racemic FTC butyrate (34) was required for the synthesis of the antiviral drug emtricitabine (Emtriva) (Scheme 7.15) a nucleoside reverse transcriptase inhibitor targeted for treatment of human immunodeficiency virus (HIV) and hepatitis infections [35]. The racemic FTC butyrate ester (34) was treated with immobilized cholesterol esterase, which cleaved the required isomer to the corresponding alcohol (-) 35 with 91% and 52% conversion [36]. The product was isolated as the hydrochloride salt to give 31% yield (98% ) from the 8 kg demonstration. The esterase was immobilized by precipitation onto an accurel polypropylene support using acetone followed by cross linking with glutaralde-... 

Assays for the determination of cholesterol in routine clinical laboratories include cholesterol esterase and thus quantify total cholesterol (i.e., unesterified and es-terified cholesterol). However, specific assays are also available that lack cholesterol esterase and hence allow the determination of unesterified or free cholesterol. The difference between total and unesterified cholesterol gives the concentration of cholesterol esters. 

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. ... 

The endoplasmic reticulum is composed of a convoluted network of channels and so has a large surface area. Apart from cytochromes P-450, the endoplasmic reticulum has many enzymes and functions, besides the metabolism of foreign compounds. These include the synthesis of proteins and triglycerides and other aspects of lipid metabolism and fatty acid metabolism. Specific enzymes present on the endoplasmic reticulum include cholesterol esterase, azo reductase, glucuronosyl transferase, NADPH cytochromes P-450 reductase and NADH cytochrome b5 reductase and cytochrome b5. A FAD-containing monooxygenase is also found in the endoplasmic reticulum, and this is discussed later in this chapter. 

Cholesteryl ester degradation Most dietary cholesterol is present in the free (nonesterified) form, with ten to fifteen percent present in the esterified form. Cholesteryl esters are hydrolyzed by pancreatic cholesterol ester hydrolase (cholesterol esterase), which produces cholesterol plus free fatty acids (see Figure 15.2). Cholesteryl esteh hydrolase activity is greatly increased in the presence of bile salts. ... 

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