Multiple Forms of Esterase in Vertebrate Blood Plasma*

Augustinsson, Klas‐Bertil

doi:10.1111/j.1749-6632.1961.tb35578.x

Cited by 289 publications

(32 citation statements)

References 29 publications

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“…Esterases were initially classified into three groups on the basis of substrate specificity and sensitivity to various inhibitors. However, the enzymes exhibit overlapping substrate specificity (2,6), leading to problems in identification and classification (3,31). Arylesterases, or A-esterases, are not inhibited by organophosphates such as paraoxon, whereas carboxylesterases, or B-esterases (serine esterases), are inhibited by organophosphates, and C-esterases are inhibited by organophosphates and eserine.…”

mentioning

confidence: 99%

A Novel Thermostable Arylesterase from the ArchaeonSulfolobus solfataricusP1: Purification, Characterization, and Expression

2008

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A novel thermostable arylesterase, a 35-kDa monomeric enzyme, was purified from the thermoacidophilic archaeon Sulfolobus solfataricus P1. The optimum temperature and pH were 94°C and 7.0, respectively. The enzyme displayed remarkable thermostability: it retained 52% of its activity after 50 h of incubation at 90°C. In addition, the purified enzyme showed high stability against denaturing agents, including various detergents, urea, and organic solvents. The enzyme has broad substrate specificity besides showing an arylesterase activity toward aromatic esters: it exhibits not only carboxylesterase activity toward tributyrin and p-nitrophenyl esters containing unsubstituted fatty acids from butyrate (C 4 ) to palmitate (C 16 ), but also paraoxonase activity toward organophosphates such as p-nitrophenylphosphate, paraoxon, and methylparaoxon. The k cat /K m ratios of the enzyme for phenyl acetate and paraoxon, the two most preferable substrates among all tested, were 30.6 and 119.4 s ؊1 ⅐ M ؊1 , respectively. The arylesterase gene consists of 918 bp corresponding to 306 amino acid residues. The deduced amino acid sequence shares 34% identity with that of arylesterase from Acinetobacter sp. strain ADP1. Furthermore, we successfully expressed active recombinant S. solfataricus arylesterase in Escherichia coli. Together, our results show that the enzyme is a serine esterase belonging to the A-esterases and contains a catalytic triad composed of Ser156, Asp251, and His281 in the active site.Sulfolobus solfataricus P1 (DSM1616), an extreme thermoacidophilic archaeon, inhabits sulfur-rich volcanic hot springs in a high-temperature and low-pH environment (10). Enzymes from thermoacidophilic archaea have attracted considerable attention among researchers because of the significance of their evolutionary phylogeny, the structural and functional stability of their enzymes despite their extreme environments, and the broad applications in biotechnology and industry available due to their special properties (23,44).Esterases (ester hydrolases) (EC 3.1

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confidence: 99%

A Novel Thermostable Arylesterase from the ArchaeonSulfolobus solfataricusP1: Purification, Characterization, and Expression

2008

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“…Unfortunately, because these widely occurring enzymes exhibit broad and overlapping substrate specificity toward esters and amides, and because, in many cases, their exact physiological role remains unclear, their classification is difficult [63][64][65][66][67][68][69]. According to an older but still used classification system [70], the more important subclasses include carboxylesterase, EC 3.1.1.1 (carboxylic-ester hydrolase, ali-esterase, B-esterase, monobutyrase, cocaine esterase, and so on); arylesterase, EC 3.1.1.2 (A-esterase, paraoxonase); acetylcholi- Figure 2.…”

Section: Enzymatic Hydrolysismentioning

confidence: 99%

“…18) has antiproliferative and cell differentiation activities that are of potential therapeutic use if sufficiently separable from the undesirable calcemic activity. Analogs such as maxacalcitol (63) have been developed along these lines for treatment of various diseases such as psoriasis, secondary hyperparathyroidism, and osteoporosis, but they still require careful administration due to potential toxicity. Introduction of a 16 double bond in such structures was explored by a group at Chugai Pharmaceutical Company to accelerate the oxidative metabolism in liver, Figure 18.…”

Section: Softmentioning

confidence: 99%

“…Esterase activity not only depends on the substrate but also shows strong interspecies, interindividual, and interorgan variability [63,69,[80][81][82][83]. Aliphatic esters (e.g., clevidipine, esmolol, isocarbacyclin methyl ester TEI-9090, remifentanil, and soft cannabinoid analogs) tend to be metabolized much faster by rodents (rats and guinea pigs) than by humans [80,81,[84][85][86][87][88][89].…”

Section: Enzymatic Hydrolysismentioning

confidence: 99%

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Retrometabolism‐Based Drug Design and Targeting

Bodor

Buchwald

2010

Burger's Medicinal Chemistry and Drug Discovery

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Retrometabolic drug design (RMDD) approaches are systematic methodologies aimed to design safe compounds with an improved therapeutic index. RMDDs thoroughly integrate structure– activity and structure‐metabolism considerations into the entire design process and incorporate two major concepts aimed to design soft drugs and chemical delivery systems, respectively. Soft drugs (SDs) are new, active therapeutic agents designed to undergo predictable metabolism resulting in inactive metabolites after exerting their desired therapeutic effect(s). Chemical delivery systems (CDSs) are biologically inert molecules that provide enhanced and targeted delivery of an active drug to a particular organ or site through a designed sequential metabolism that involves several steps. Here, we present a comprehensive review including a general overview of the RMDD principles and a large number of specific examples from various pharmacological areas, including many recent developments, to illustrate RMDD concepts. Whenever possible, the rationale for the design as well as the pharmacokinetic and pharmacodynamic properties of the new therapeutic agents are briefly summarized and compared to those of the other compounds used in the same field.

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“…PON gene mutation is associated with an increased risk of stroke [10]. ARE is a carboxylesterase and catalyses splitting of aromatic esters of fatty acids [11]. Moreover, ARE is an isoenzyme of PON, showing specific activity against phenyl acetate [12].…”

Section: Introductionmentioning

confidence: 99%

Serum Paraoxonase/Arylesterase Activity Affects Outcome in Ischemic Stroke Patients

et al. 2011

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Background: The severity of neurological deficits arising from ischemic stroke may be related to serum redox homeostasis. The aim of this study was to estimate the effect of serum paraoxonase (PON), arylesterase (ARE) activities and conjugated dienes (CD) on patient outcome during a 1-year follow-up period. Methods: The study included 468 consecutive ischemic stroke patients (251 males, 217 females) with an average age of 67.5 ± 12.4 years. Clinical evaluation was based on vital signs, National Institutes of Health Stroke Scale (NIHSS) scored at the time of admission and on the 7th day after stroke, as well as modified Rankin scale (mRS) and Barthel index (BI) scored at 30, 90, 180 and 360 days after stroke onset. Serum PON, ARE activities and CD concentration were measured with the use of spectrophotometric methods. Results: Serum PON activity alone correlated directly with a favorable outcome during a 3-month observation period. Serum ARE activity correlated directly only with the mRS score in a 1-year observation. PON/ARE ratio showed the strongest direct correlation with favorable stroke outcome expressed by BI and inverse correlation with mRS as compared to serum PON or ARE activities assessed alone. PON/ARE affected the NIHSS score on admission (rS = –0.119, p = 0.014) and on the 7th day after stroke (rS = 0.120, p = 0.015); it also showed an association with the BI and mRS on the 30th (rS = 0.145, p = 0.007 and rS = –0.098, p = 0.049, respectively), 90th (rS = 0.147, p = 0.009, rS = –0.133, p = 0.008, respectively), as well as 180th, and 360th day after stroke. We did not find correlations between the serum CD concentration and stroke outcome. Conclusion: The PON/ARE ratio is an important predictor of ischemic stroke outcome and can be used in clinical practice rather than evaluating either PON or ARE activity alone.

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Multiple Forms of Esterase in Vertebrate Blood Plasma*

Cited by 289 publications

References 29 publications

A Novel Thermostable Arylesterase from the ArchaeonSulfolobus solfataricusP1: Purification, Characterization, and Expression

A Novel Thermostable Arylesterase from the ArchaeonSulfolobus solfataricusP1: Purification, Characterization, and Expression

Retrometabolism‐Based Drug Design and Targeting

Serum Paraoxonase/Arylesterase Activity Affects Outcome in Ischemic Stroke Patients

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