Esterases carboxyl esterase

The action of esterases consists essentially in the hydrolysis (or synthesis) of carboxylic acid esters according to the equation ... 

Chirazymes. These are commercially available enzymes e.g. lipases, esterases, that can be used for the preparation of a variety of optically active carboxylic acids, alcohols and amines. They can cause regio and stereospecific hydrolysis and do not require cofactors. Some can be used also for esterification or transesterification in neat organic solvents. The proteases, amidases and oxidases are obtained from bacteria or fungi, whereas esterases are from pig liver and thermophilic bacteria. For preparative work the enzymes are covalently bound to a carrier and do not therefore contaminate the reaction products. Chirazymes are available form Roche Molecular Biochemicals and are used without further purification. 

This group was designed as an enzymatically cleavable protective group. Cleavage is achieved using an esterase present in mouse plasma or hog liver carboxylate esterase. " ... 

Hayama et al.132 discussed the catalytic effects of silver ion-polyacrylic add systems toward the hydrolyses of 2,4-dinitrophenylvinylacetate 84 (DNPVA) by using the weak nudeophilicity of carboxylic groups and the change-transfer interactions between olefinie esters and silver ions133Metal complexes of basic polyelectrolytes are also stimulating as esterase models. Hatano etal. 34, 13S) reported that some copper(II)-poly-L-lysine complexes were active for the hydrolyses of amino acid esters, such as D- and L-phenylalanine methyl ester 85 (PAM). They... 

A different task was pursued by the CM of CsA with various maleates 339 [ 148]. The CM demanded in this case the highly active Hoveyda catalyst D, that exhibits potency not reached by the phosphine-containing catalysts C and E. Under the conditions given in Scheme 65, metathesis with maleates 339 led (E)-selectively to the a,/J-unsaturated ester derivatives 340 in high yield. Compounds 340 still demonstrated activity comparable to that of CsA and are thus potential soft drugs via esterase-mediated biotransformation to the corresponding inactive carboxylic acids 341. 

Fluorescein absorbance is sensitive to pH. This property is utilized to measure cytosolic pH changes. Fluorescein derivatives that contain esters on the carboxyl groups have been constructed. These compounds partition through the cell membrane and, once inside the cell, the esters are cleaved by nonspecific esterases in the cytosol, leaving free carboxyl groups thus the probe cannot diffuse out of the cell (or at least does so slowly). Commonly used derivatives are 6-carboxyfluorescein (21-23) and the more recently developed probe 2, 7 -bis(2-carboxyethyl)-5(and-6)-carboxyfluorescein (13, 24,25). 

Esterase Cleavage of esters of carboxylic adds Acetyldigoxin... 

Irinotecan is a prodmg, and hydrolysis of irinotecan by the high-affinity carboxyl-esterase-2 enzyme in many normal tissues and tumors is responsible for activa-... 

Carboxylesterases and amidases catalyze hydrolysis of carboxy esters and carboxy amides to the corresponding carboxylic acids and alcohols or amines. In general those enzymes capable of catalyzing hydrolysis of carboxy esters are also amidases, and vice versa (110). The role of these enzymes in metabolsim of drugs and insecticides has been reviewed (111, 112). In addition to the interest in mammalian metabolism of drugs and environmental chemicals, microbial esterases have been used for enantioselective hydrolyses (113, 114). 

Estane, commercial block copolymer, 7 648t Ester—acid interchange, 10 492-493 Ester—alcohol interchange, 10 491—492 Esterases, 3 675-676 Ester bonds, in the wood cell wall, 21 15 Ester carboxylates, 24 144, 145 Ester-ester interchange, 10 493 Ester hydrolysis, 10 497, 502—503 Esterifiable acids, 10 490 Esterification, 9 283, 320 10 471-496. 

There are few drugs that are thioesters, but you may recall that one of the intermediates in the oxidation of aldehydes by aldehyde dehydrogenase is a thioester involving the thiol of the enzyme (Fig. 30 in Chapter 4), which is readily hydrolyzed back to the native form of the enzyme, a thiol, and the carboxylic acid product. Some drugs that are carboxylic acids, such as enaloprilate, are administered as ester prodrugs (enalopril), which are more readily absorbed from the intestine than the carboxylic acid and are then readily hydrolyzed to the active drug by esterases as mentioned in Chapter 1 (Fig. 1 in Chapter 1). 

An example of esterase behaviour is provided by a catalytic antibody developed by Tramontano et al. (1988), using a phosphonate transition state analogue [53] as the hapten. The antibody cleaves the carboxylic ester [54, R = Me] with enzyme-like efficiency (kc/ku = 6.25 X 106 = 1.5 mM ... 

We must stress that organo-phosphorus compounds are not specific inhibitors for the cholinesterases, but are rather inhibitors for enzymes possessing carboxylic esterase activity. All the enzymes mentioned below will hydrolyse carboxylic esters. However, not all esterases are inhibited, for example, A-esterase which hydrolyses phenyl acetate is not inhibited by organo-phosphorus compounds. 

A selection of carboxylic ester hydrolases (EC 3.1.1) of major or more-modest significance in xenobiotic metabolism is given in Table 2.5. The recommendations of the Enzyme Nomenclature Committee on the classification of esterases cannot be considered completely satisfactory, but, even after decades of debate, a more satisfactory classification system remains to be proposed [56] [57], The main difficulties with esterase classification have been summarized as follows [58],... 

Carboxylesterase Carboxylic ester hydrolase, nonspecific carboxylesterase, ali-esterase, B-esterase Aliphatic esters... 

B. Kleingeist, R. Bocker, G. Geisslinger, R. Brugger, In vitro Metabolism of Flumaze-nil by a Human Liver Carboxyl Esterase and Cytochrome P450 , Exp. Toxicol. Pathol. 1996, 48(Suppl. II), 194-201. 

Another therapeutic class to be briefly discussed is that of the lipid-lowering agents known as fibrates, e.g., clofibrate and fenofibrate (8.5). Here also, the acidic metabolite is the active form clofibrate (an ethyl ester) is rapidly hydrolyzed to clofibric acid by liver carboxylesterases and blood esterases [11], Human metabolic studies of fenofibrate (8.5), the isopropyl ester of fenofibric acid, showed incomplete absorption after oral administration, while hydrolysis of the absorbed fraction was quantitative [12], This was followed by other reactions of biotransformation, mainly glucuronidation of the carboxylic acid group. 

Phosphinates are a class of organophosphorus compounds, the metabolism of which has received less attention than that of phosphates (see above) or phosphorothioates and P-halidc compounds (see below). Many phosphinates are rapid but transient inhibitors of acetylcholinesterase and carboxyl-esterases. And like organophosphates and phosphonates, phosphinates are substrates of arylesterases (EC 3.1.1.2). This is exemplified by 4-nitrophen-yl ethyl(phenyl)phosphinate (9.62), whose (-)-enantiomer was hydrolyzed by rabbit serum arylesterase almost 10 times faster than the (+)-enantiomer [133],... 

In one case, a small peptide with enzyme-like capability has been claimed. On the basis of model building and conformation studies, the peptide Glu-Phe-Ala-Ala-Glu-Glu-Phe-Ala-Ser-Phe was synthesized in the hope that the carboxyl groups in the center of the model would act like the carboxyl groups in lysozyme 17). The kinetic data in this article come from assays of cell wall lysis of M. lysodeikticus, chitin hydrolysis, and dextran hydrolysis. All of these assays are turbidimetric. Although details of the assay procedures were not given, the final equilibrium positions are apparently different for the reaction catalyzed by lysozyme and the reaction catalyzed by the decapeptide. Similar peptide models for proteases were made on the basis of empirical rules for predicting polypeptide conformations. These materials had no amidase activity and esterase activity only slightly better than that of histidine 59, 60). 

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