Arylesterases

Mackness, M.I., Thompson, H.M., and Walker, C.H. (1987). Distinction between A esterases and arylesterases and implications for esterase classification. Biochemical Journal 245, 293-296. 

Haley, R., W., Billecke, S., S., and La Du, B., N., Association of low PON1 type Q (type A) arylesterase activity with neurological symptom complexes in Gulf War veterans, Toxicol. Appl. Pharmacol., 1999, 157,227-33. 

Arylesterase Aryl-ester hydrolase, A-esterase Aromatic 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. 

The distinction between aryldialkylphosphatase, also called paraoxonase (Sect. 2.5.6 and 3.7), and arylesterase was introduced in the last printed revision of the nomenclature recommendations [1], Arylesterases (EC 3.1.1.2) act on many phenolic esters [66] [67] aryldialkylphosphatases (aryltriphos-... 

K. N. Gan, A. Smolen, H. W. Eckerson, B. N. La Du, Purification of Human Serum Paraoxonase/Arylesterase. Evidence for One Esterase Catalyzing Both Activities , Drug Metab. Dispos. 1991,19, 100-106. 

S. L. Primo-Parmo, R. C. Sorenson, J. Teiber, B. N. La Du, The Human Serum Para-oxonase/Arylesterase Gene (PON1) is One Member of a Multigene Family , Genomics 1996, 33, 498-507. 

A variety of hydrolases catalyze the hydrolysis of acetylsalicylic acid. In humans, high activities have been seen with membrane-bound and cytosolic carboxylesterases (EC 3.1.1.1), plasma cholinesterase (EC 3.1.1.8), and red blood cell arylesterases (EC 3.1.1.2), whereas nonenzymatic hydrolysis appears to contribute to a small percentage of the total salicylic acid formed [76a] [82], A solution of serum albumin also displayed weak hydrolytic activity toward the drug, but, under the conditions of the study, binding to serum albumin decreased chemical hydrolysis at 37° and pH 7.4 from tm 12 1 h when unbound to 27 3 h for the fully bound drug [83], In contrast, binding to serum albumin increased by >50% the rate of carboxylesterase-catalyzed hydrolysis, as seen in buffers containing the hydrolase with or without albumin. It has been postulated that either bound acetylsalicylic acid is more susceptible to enzyme hydrolysis, or the protein directly activates the enzyme. 

In vitro studies were also conducted to discover the enzymes responsible for bioactivation of benazepril. With different preparations and eserine as an inhibitor, the involvement of arylesterases (EC 3.1.1.2) and cholinesterases (EC 3.1.1.8) was ruled out, while that of carboxylesterases (EC 3.1.1.1) was... 

Recent studies with quinoline-4-carboxylic acid angiotensin II receptor antagonists have confirmed the interest of (oxodioxolyl)methyl esters as prodrugs with improved oral bioavailability and efficacy in laboratory animals [79], Olmesartan, another angiotensin II receptor antagonist, has also been derivatized to a (5-methyl-2-oxo-l,3-dioxol-4-yl)methyl carboxylate designated as olmesartan medoxomil [80], In this case, both human serum albumin and arylesterase (presumably EC 3.1.1.2, although paraoxonase cannot be excluded) were shown to be involved in hydrolysis. 

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],... 

A. F. Hernandez, M. C. Gonzalvo, F. Gil, E. Villanueva, A. Pla, Divergent Effects of Classical Inducers on Rat Plasma and Microsomal Fraction Paraoxonase and Arylesterase , Environ. Toxicol. Pharmacol. 1997, 3, 83-86. 

Other metabolic enzymes that show polymorphic differences in that they can occur as genetic high-activity and low-activity variants include acetylcholinesterase, butyrylcholinesterases, flavin-dependent monooxygenase, alcohol dehydrogenase, epoxide hydrolase, and arylesterase (Beltoft et al. 2001). 

C. T. Yuen, R. G. Price, A. C. Richardson, and P. F. G. Praill, The assay of arylesterase in serum using two new colorimetric substrates, (n-nitrostyrylacetate and propionate, Clin. Chem. Acta (1981) 99—105. 

A-type carboxylic ester hydrolases (arylesterases EC 3.1.1.2), which hydrolyse aromatic esters, e.g. phenylacetate they show little activity on tributyrin, and are not inhibited by organophosphates. 

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 Arylesterase Triacylglycerol lipase Phospholipase A2 Lysophospholipase Acetylesterase Acetylcholinesterase Cholinesterase... 

Gan, K.N., et al. 1991. Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos 19 100. 

Haagen, L., and A. Brock. 1992. A new automated method for phenotyping arylesterase (EC 3.1.1.2) based upon inhibition of enzymatic hydrolysis of 4-nitrophenyl acetate by phenyl acetate. Eur J Clin Chem Clin Biochem 30 391. 

B.N. La Du, S. Adkins, Analysis of Serum Para-oxonase/Arylesterase Polymorphism in Some Sudanese Families , in Ethnic Differences in Reactions to Drugs and Xenobiotics, eds. W. Kalow, H.W. Goedde, D.P. Agarwal, Alan R. Liss, New York, 87-98,1986. 

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