Carboxyl esterase

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. " ... 

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-... 

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. 

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. 

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],... 

UGTIAI has an important role in the metabolism of irinotecan, etoposide, epiru-bicine, and tipifamib. Irinotecan is a camptothecin derivative used in the treatment of metastatic colon cancer. Irinotecan is a prodrug since it is activated to Ethyl-10-hydroxycamptothecin (SN-38) by carboxyl esterase to exert its antitumor activity mediated by the inhibition of topoisomerase I. SN-38 undergoes UGTIAI-catalyzed glucuronide conjugation to form the inactive SN-38 glucuronide (SN-38G). 

Carboxylic esterases and carboxylic lipases have been tested with phosphate esters, but without success. This is easy to understand on the basis of the mechanism which... 

Figure 2.3 Carboxyl esterases and carboxyl lipases both act on carboxylic...

The hydrolysis of some amides may be catalyzed by a liver microsomal carboxyl esterase, as is the case with phenacetin (Fig. 4.44). Hydrolysis of the acetylamino group, resulting in deacetylation, is known to be important in the toxicity of a number of compounds. For example, the deacetylated metabolites of phenacetin are thought to be responsible for its toxicity, the oxidation of hemoglobin to methemoglobin. This toxic effect occasionally occurs in subjects taking therapeutic doses of the drug and who have a deficiency in the normal pathway of metabolism of phenacetin to paracetamol. Consequently, more phenacetin is metabolized by deacetylation and subsequent oxidation to toxic metabolites (chap. 5, Fig. 24). 

Figure 5 Production of S-ibuprofen with a racemization step and an enzymatic conversion using the carboxyl esterase enzyme.

Lipases (triacylglycerol acyl hydrolases, EC 3.1.1.3), have been well established as a valuable catalyst in organic synthesis.12 They are usually distinguished from carboxyl esterases (EC 3.1.1.1) by their substrate spectra, i.e. esterases prefer water soluble substrates and lipases show significantly higher activity towards their natural substrates,... 

Extrahepatic / renal Variable (e.g., plasma carboxyl-esterases, intestinal CYP3A4) RES (vascular endothelium and phagocytic blood cells)... 

Thus far no sex pheromone has been described in the Phasmida. Some phasmids produce toxic monoterpenes in typical Class III integumentary glands located behind the head (e.g. Happ et al., 1966). The glands exhibit lipid reserves, carboxylic esterases, phosphatases, alcohol dehydrogenase, and a mevalonate kinase, all of which are suggested to be involved in the production of the toxic compounds (Happ et al., 1966). 

There emerges a very complex picture of three hormones synthesized and secreted at variable rates, competing for carrier binding proteins, presumed receptor proteins, epoxide hydratase and carboxyl esterase enzymes (35,36). It is possible experimentally to measure tEe timing of critical periods for larval determination and to measure total levels of JH at these critical periods although both measurements involve extreme difficulty. Approaches to this were described recently by G.B. Staal (3 7) using third instar larvae of the tobacco hornworm moth, Manduca sexta, which were allatectomized and raised on JH impregnated diets as an experimentally reproducible method of JH therapy. 

Deeth, H.C. 1978. Fluorimetric detection of carboxyl-esterase activity in milk. Proc. 20th Int. Dairy Cong. (Paris) E, 364-365. 

During natural evolution, a broad variety of enzymes has been developed, which are classified according to the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB). Thus, for each type of characterized enzyme an EC (Enzyme Commission) number has been provided (see http // www.expasy.ch/enzyme/). For instance, all hydrolases have EC number 3 and further subdivisions are provided by three additional digits, e.g. all lipases (official name triacylglycerol lipases) have the EC number 3.1.1.3 and are thus distinguished from esterases (official name carboxyl esterases) having the EC number 3.1.1.1. This classification is based on the substrate (and cofactor) specificity of an enzyme only, however often very similar amino acid sequences and also related three-dimensional structures can be observed. 

Fig. 11. Electrophoretic distribution in agar of gastric mucosal extract protein (A) protease activity at pH 2.2 (B) carboxylic esterase activity (C) and immuno-electrophoretic pattern (D). The relative mobility is shown at the bottom (UR) with 0 representing the location of the uncharged dextran, levan and 1 the migration of human serum albumin. The zones of mobility (Z), arbitrarily defined on the basis of protein distribution, are indicated at the top. Each antigen and enzyme is designated by the zone in which it is found. The antigens are alsc designated by a letter. From Kushner et al. (K32).

Rapp with Burtin (R1) found 5 carboxylesterases in the gastric human mucosa on agar gel electrophoresis (see Fig. 11) using special substrates. These carboxyl esterases were decreased and differently distributed in the gastric mucosa of patients with gastric cancer. 

In subsequent work, Rapp and Burtin (Rla) studied the gastric mucosa extract from 30 controls and 7 cancerous stomachs by immunoelectro-phoresis. In the extracts of cancerous stomachs, the first 2 anodic fractions disappeared, fractions 3, 6, and 7 decreased, while the most centrally located fraction (4) was increased. Three out of five zones of carboxylic esterase activity disappeared in cancer juices, while all of the 4 zones of proteolytic activity were either absent or markedly decreased. The adjacent gastric mucosa, not revealing the carcinomatous infiltration, showed similar abnormalities. 

Table 5 Enzymatic Resolution of Alcohols by Transesterification with Hog Liver Carboxylate Esterase (HLCE)...

Stott WT, McKenna MJ. 1985. Hydrolysis of several glycol ether acetates and acrylate esters by nasal mucosal carboxyl-esterase in vitro. Fundam. Appl. Toxicol. 5 399 104... 

As families containing the double displacement glycohydrolases can also contain transglycosylases, so CE 1, which contains double-displacement carboxyl esterases, also contains transacylases. Trehalose [a-D-Glcp-(l<->l)-a-D-Glcp] esterified on 06 with mycolic acid plays a role in maintaining the hydrophobic exteriors of the tubercle bacterium Mycobacterium tuberculosis, and the crystal structure of three related mycoloyl transesterases are... 

Chatthopadhay DP, Dighe SK, Nashikkar AB et al. (1986). Species differences in the in vitro inhibition of grain acetylcholinesterase and carboxyl esterase by mipafox, paraoxon and soman. Pest Biochem Physiol, 26, 202-208. 

Metabolism of the local anaesthetic procaine provides an example of esterase action, as shown in figure 4.42. This hydrolysis may be carried out by both a plasma esterase and a microsomal enzyme. The insecticide malathion is metabolized by a carboxyl esterase in mammals, rather than undergoing oxidative desulphuration as in insects (figure 5,10). 

The juvenile hormones are easily degraded by membrane-bound epoxide hydrolases and carboxyl esterases. The degradation products have no hormone activity and are excreted as sulfates. A carrier protein protects it from degradation, and its concentration is important for the regulation of the amount of active JH. 

Many pesticides are esters or amides that can be activated or inactivated by hydrolysis. The enzymes that catalyze the hydrolysis of pesticides that are esters or amides are esterases and amidases. These enzymes have the amino acid serine or cysteine in the active site. The catalytic process involves a transient acylation of the OH or SH group in serin or cystein. The organo-phosphorus and carbamate insecticides acylate OH groups irreversibly and thus inhibit a number of hydrolases, although many phosphorylated or carbamoylated esterases are deacylated very quickly, and so serve as hydrolytic enzymes for these compounds. An enzyme called arylesterase splits paraoxon into 4-nitrophenol and diethyl-phosphate. This enzyme has cysteine in the active site and is inhibited by mercury(ll) salts. Arylesterase is present in human plasma and is important to reduce the toxicity of paraoxon that nevertheless is very toxic. A paraoxon-splitting enzyme is also abundant in earthworms and probably contributes to paraoxon s low earthworm toxicity. Malathion has low mammalian toxicity because a carboxyl esterase that can use malathion as a substrate is abundant in the mammalian liver. It is not present in insects, and this is the reason for the favorable selectivity index of this pesticide. 

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