Aryl ester hydrolase

Arylesterase Aryl-ester hydrolase, A-esterase Aromatic esters... 

Monoamine oxidase and aryl-ester hydrolase are marker enzymes of mitochondria (outer membranes) and microsomes, respectively. Values are expressed as nmol / min per mg protein and are means S.E.M (n. (X)4 4)... 

As shown in Table 1, crude mitochondrial fractions prepared by differential centrifugation (as other slightly different conventional methods) appeared to exhibit pronounced aryl-ester hydrolase (EC 3.1.1.2) activity. As this activity was found specifically in microsomes, mitochondrial fractions prepared conventionally are always contaminated by microsomes. In mitochondrial fractions isolated on Percoll gradient imder the conditions precisely described in the Materials and Methods section, the above microsomal activity was extremely low. The pattern was similar for acyl-CoA Hgase (ACL), its specific activity was very high in microsomal fractions and almost negligible in PercoU-purified mitochondrial fractions (Fig. 1). Taking into account the specific activity of aryl-ester hydrolase in microsomal fractions, the amount of microsomal protein present in purified mitochondrial fractions could be estimated around 2% and was sufficient to account for the residual ACL activity in these fractions. It was, therefore, clear that a totally pure liver mitochondrial fraction could not esterify fatty acids with CoA. 

Tarzia et al. [69, 70] have recently reported the FAAH inhibitory activity of a series of alkylcarbamic acid aryl esters. The starting point for their studies was the known serine hydrolase inhibitor carbamyl (51) that had no activity at FAAH. Replacement of the small methyl group of carbamyl (51) with more lipophilic groups and, in particular, bulky lipophilic groups resulted in increased affinity at FAAH (Table 6.6). Exploration of replacements of the naphthyl moiety revealed that replacement with a biphenyl group resulted in improved affinity and in particular, the 3-biphenylyl group proved effective... 

Two examples of aryl esters are given in Table 8.5, namely the 4-chloro-phenyl and 4-nitrophenyl esters of nicotinic acid (8.33). Under physiological conditions of pH and temperature, these two compounds were clearly much more susceptible to chemical hydrolysis than the alkyl and arylalkyl esters in Table 8.5. Their affinity for carboxylesterase and human plasma hydrolases, as assessed by the Michaelis constant Km, was generally higher, while nothing can be said regarding Vmax values. 

Tarzia, G., Duranti, A., Tontini, A., Piersanti, G., Mor, M., Rivara, S., Plazzi, P. V., Park, C., Kathuria, S., and Piomelli, D. (2003). Design, synthesis, and structure-activity relationships of alkylcarbamic acid aryl esters, a new class of fatty acidamide hydrolase inhibitors. J. Med. Chem. 

S, Piomelli D (2003) Design, synthesis, and structure-activity relationships of alkylcar-bamic acid aryl esters, a new class of fatty acid amide hydrolase inhibitors. J Med Chem 46 2352-2360... 

Acetylsalicylate deacetylase Aspirin esterase, aspirin hydrolase Acetyl esters of aryl alcohols, negatively charged esters... 

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. 

Simple alkyl or aryl thioesters are commonly assayed as substrates of hydrolases, witness the hydrolysis of phenyl thioesters by horse serum carbox-ylesterase [150], For most substrates investigated, e.g., phenyl thioacetate, phenyl thiopropionate, and phenyl thiobutyrate (7.66, R = Me, Et, and Bu, respectively), kcat values were found, which were a few times larger than those of corresponding nitrophenyl esters, whereas the affinities were lower by approximately one order of magnitude. Methyl and phenyl esters of various linear thioacids were also found to be good substrates of mammalian liver carboxylesterases and serum cholinesterases [151]. 

The types of enzymes that bring about hydrolysis are hydrolase enzymes. Like most enzymes involved in the metabolism of xenobiotic compounds, hydrolase enzymes occur prominently in the liver. They also occur in tissue lining the intestines, nervous tissue, blood plasma, the kidney, and muscle tissue. Enzymes that enable the hydrolysis of esters are called esterases, and those that hydrolyze amides are amidases. Aromatic esters are hydrolyzed by the action of aryl esterases and alkyl esters by aliphatic esterases. Hydrolysis products of xenobiotic compounds may be either more or less toxic than the parent compounds. 

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