Aryl esterase

In 1982, the Schaap group demonstrated that chemiluminescence can be induced by the addition of a base to dioxetanes bearing a phenolic substituent [11]. Herein, the same group presents a method utilizing aryl esterase to catalyze the cleavage of a naphthyl acetate-substituted dioxetane in aqueous buffer at ambient... 

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. 

Haley RW, Kurt TL, Horn ] Is there a Gulf War syndrome Searching for syndromes by factor analysis of symptoms. JAMA 277 215-222, 1997b Haley RW, Billecke S, La Du BN Association of low PON1 Type Q (Type A) aryl-esterase activity with neurologic symptom complexes in Gulf War veterans. Toxicol Appl Pharmacol 157 227-233, 1999... 

Schaap, A. P., Handley, R. S., and Giri, B. P., Chemical and enzymatic triggering of 1,2-dioxetanes 1 Aryl esterase-catalyzed chemiluminescence from a naphthyl acetate-substituted dioxetane. Tetrahedron Lett. 28, 935-938 (1987). 

Mammalian PON1 (serum paraoxonase) Lipo-lactonase - aliphatic 5-, PON1 Aryl esterase (phenyl 91,92... 

Aryl esterase (2-naphthyl acetate, 88, 87 500) lactonase (dihydrocoumarin, 6.5 x 10 )... 

Organophosphate Ester Hydraulic Fluids. In a study of nonspecific monocyte esterase staining, humans who were exposed to aryl phosphates occupationally showed very slight esterase inhibition (Mandel et al. 1959). 

Mammalian esterases have been classified into three groups according to specificity for substates and inhibitors (110). In terms of overall hydrolytic activity in mammals, the most important class of esterases is that of the B-esterases, which are principally active with aliphatic esters and amides. A-Esterases are important for aromatic esters and organophosphorus esters, and C-esterases are active with acetyl esters. In general, the specificity of mammalian esterases is determined by the nature of substituent groups (acetyl, alkyl, or aryl) rather than the heteroatom (O, N, or S) that is adjacent to the carboxy group. That is, the same esterase would likely catalyze hydrolysis of an ester, amide, or thioester as long as the substituents were identical except for the heteroatom (110). 

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

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

The mechanism by which A-esterases hydrolyze organophosphates is not completely understood. Involvement of a phosphorylated active-site cysteine and displacement of an activated H20 molecule are two possible hypotheses (see Sect. 3.7.1) [56], A-Esterases comprise enzymes that hydrolyze aryl esters, paraoxon (2.2) and related organophosphate pesticides, and diisopropyl-fluorophosphate (DFP, diisopropyl phosphorofluoridate, 2.3) and related compounds, including nerve gases. These enzymes are found in the current nomenclature listed under arylesterases, aryldialkylphosphatase, and diisop-ropyl-fluorophosphatase. 

Frechet and coworkers have popularized poly(aryl ether) dendrimers and polyester dendrimers (Fig. 13.7), which have been widely used (Hawker and Frechet 1990 Dire et al. 1998). Addition of the aromatic rings adds rigidity to the dendiimer framework that is lacking in the PPI and PAMAM dendrimers. The polyester dendrimers may be more like the PPIs and PAMAMs in terms of rigidity, but the ester linkages enable degradation of the polyester dendrimers by esterases in vivo. Thus, the biological stability of the PAMAMs and the polyester frameworks is quite different. 

Carbamates are substituted esters of carbamic acid (NH2COOH) with aliphatic or aromatic substituents on the oxygen and nitrogen atoms. Carbamate insecticides have an aryl or oxime N-methylcarbamate structure, and their mode of action is based on the inhibition of the enzyme acethylcholine esterase (1). However, this inhibition is reversible, and recovery from sublethal doses occurs rapidly. Some carbamate fungicides have a dithio, bisdithio, or benzimidazole carbamate basic structure, and dithiocarbamate fungicides inhibit the enzyme aldehyde deshydro-genase (2). The herbicides have an /V-alkylthiocarbamate or A-phenylcarbamate structure and interfere with photosynthetic activity or affect meristematic activity or lipid metabolism (3). Representative structures of carbamate pesticides are shown in Fig. 1. 

Cyclodextrins and their derivatives are already known to catalyse an enormous variety of biochemical and non-biochemical transformations. The basis of the catalysis by native (unmodified) cyciodextrins is the positioning of the reactive secondary hydroxyl groups directly at the entrance to the molecular cavity. One of the most effective reactions catalysed by cyclodextrins is the hydrolysis of aryl and phosphate esters (esterase activity). For example, the rate of hydrolysis of p-nitrophenol esters is increased by factors of up to 750 000 by /TCD. The mechanism of action of the cyclodextrin is shown in Scheme 12.2.1... 

Esterase Activity. NAD -free GAPDH catalyzes the hydrolysis of aryl esters (e.g., p-nitrophenyl acetate) at rates up to five times that of chymotrypsin (185). This reaction also proceeds via a thiolester intermediate with Cys-149 (99) and is, therefore, inhibited by iodoacetate. 

Figure 5 Two groups of NTE inhibitors Group A (upper) Induce delayed neuropath/1 Group B (lower) protect against the neuropathic potency of the upper group. R and R may be alkyl, aryl or heterocyclic substituents X is the leaving group which is ejected when the inhibitor reacts covalently with the enzyme Redrawn from Johnson, M.K., 1974 A comparison of the stmetures of inhibitors of "neurotoxic esterase". J Neurochemistry 23 786, Fig 1, Raven Press, N.Y ...

Perigaud has extended his work on the synthesis and biological activities of phosphotriester derivatives of AZT bearing a phenyl group or L-tyrosinyl residues. The novel AZT-derivatives (21a-d) also incorporating one S-pivaloyl-2-thioethyl residue were obtained via either P(III) or P(V) chemistry from the appropriate aryl precursors and evaluated for their in vitro anti-HIV activity. ECso values for their ability to inhibit HIV-1 replication in various cell culture experiments ranged between micro- and the nanomolar concentrations. S-Pivaloyl-2-thioethyl aryl phosphotriester derivatives of AZT were able to allow the efficient intracellular delivery of the parent nucleotide via their successive intracellular hydrolysis by an esterase and a phosphodiesterase. ... 

Furthermore, a useful way of assessing the magnitude of promiscuous activities is the rate acceleration iKsa/Kncm) or catalytic proficiency ( cat/- M/ uncat)- These parameters are indicative because they take into account the inherent reactivity of the substrate. In many cases, promiscuous activities occur, or are measured, with highly reactive substrates. Such activities are in a way expected. However, there are many cases in which promiscuous activities take place with substrates that are less activated than the native one. Examples include, the amidase activity of esterases such as lipases (Table 1, entry 7), the phosphodiesterase activities of P. diminuta PTE and alkaline phosphatase (Table 1, entries 10 and 8), and the PTE activities or various lactonases (Table 1, entries 11-13 and the notable fact that some of these lactonases do not hydrolyze the more activated aryl esters). In such cases, the chemical challenge posed by a less activated substrate is reflected in the more favorable comparisons of rate accelerations, or catalytic proficiencies, for the native versus the promiscuous substrates. 

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