Carboxylesterase carboxyl esters

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

T. L. Huang, A. Szekacs, T. Uematsu, E. Kuwano, A. Parkinson, B. D. Hammock, Hydrolysis of Carbonates, Thiocarbonates, Carbamates, and Carboxylic Esters of a-Naph-thol, /LNaphthol, and p-Nitrophenol by Human, Rat, and Mouse Liver Carboxylesterases , Pharm. Res. 1993, 10, 639 - 648. 

In addition to these various phosphatases, carboxylic ester hydrolases interact with phosphates and/or phosphonates. The carboxylesterases (EC... 

Various esterases exist in mammalian tissues, hydrolyzing different types of esters. They have been classified as type A, B, or C on the basis of activity toward phosphate triesters. A-esterases, which include arylesterases, are not inhibited by phosphotriesters and will metabolize them by hydrolysis. Paraoxonase is a type A esterase (an organophosphatase). B-esterases are inhibited by paraoxon and have a serine group in the active site (see chap. 7). Within this group are carboxylesterases, cholinesterases, and arylamidases. C-esterases are also not inhibited by paraoxon, and the preferred substrates are acetyl esters, hence these are acetylesterases. Carboxythioesters are also hydrolyzed by esterases. Other enzymes such as trypsin and chymotrypsin may also hydrolyze certain carboxyl esters. 

Carboxylesterase Plants, moulds Carboxylic ester Alcohol + carboxylic acid... 

Mechanism of interaction of A- and B-esterases with OPC is similar. B-esterases initially form Michaelis complex with an OPC inhibitor producing phosphorylated or inhibited enzyme that either reactivates very slowly or does not reactivate at all (Figure 3) [1], However, after forming Michaelis complex with OPC A-esterases perform intensive and permanent hydrolysis of OPC and their catalytic activity and turnover rate are very high. It was already shown that carboxylesterases, as a typical B-esterase, can hydrolyze carboxylic esters that serve as functional groups in OPC such as malathion thus performing detoxication of the compound [26, 27]. 

Malathion (chemathion, mala-spray) requires conversion to malaoxon (replacement of a sulfur atom with oxygen in vivo, conferring resistance to mammalian species). Malathion can be detoxified by hydrolysis of the carboxyl ester linkage by plasma carboxylesterases, and plasma car-boxylesterase activity dictates species resistance to malathion. The detoxification reaction is much more rapid in mammals and birds than in insects. Malathion has been employed in aerial spraying of relatively populous areas for control of Mediterranean fruit flies and mosquitoes that harbor and transmit viruses harmful to human beings (e.g.. West Nile encephalitis virus). Evidence of acute toxicity from malathion arises only with suicide attempts or deliberate poisoning. 

Carboxylesterase 3.1.1.1 esters, alcohols alcohols, carboxylic acids, alcohols >100... 

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). 

In comprehensive studies, the hydrolysis of some 30 naphthyl esters by human, rat, and mouse liver carboxylesterases was investigated [43], A general trend that was apparent was that the rate of hydrolysis of a- and /3-naphthyl carbonates (7.21, R = alkyl or arylalkyl) catalyzed by human microsomes or rat hydrolases showed a tendency to decrease with increasing lipophilic-ity (range ca. 2 to 5). A similar trend was not seen with naphthyl aryl carbonates nor with a-naphthyl carboxylates. These results tell us that, even with purified enzymes and large series of substrates, it is very difficult indeed to discern sound structure-hydrolysis relationships due to the complexity of the structural and enzymatic factors involved. 

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. 

The term carboxylesterase refers to a wide variety of enzymes with both esterase and amidase activity. They cleave carboxylesters, carboxylamides, and car-boxylthioesters, producing a carboxylic acid and an alcohol or phenol (Figure 8), amine, or mercaptan, respectively. There are many different esterases, some of which are important for the hydrolysis and detoxication of toxic organophosphate esters. In general, esterases are present in almost all mammalian tissues, occur as multiple isozymes, and are concentrated in the liver. The esterase activity present in plasma is normally due to the release of these enzymes from liver. 

Based on these data, it is concluded that monoterpene esters will undergo in vivo hydrolysis in animals to yield the corresponding alcohols and carboxylic acids. Given that the carboxylesterases and lipases catalysing ester hydrolysis are present in all animals, including fish, it is concluded that monoterpene esters will be hydrolysed to yield monoterpene alcohols and simple aliphatic and aromatic acids. Once hydrolysed, the component alcohols and acids are subject to further oxidative metabolism and/or conjugation. 

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