Enzymatic detection of organophosphorus compounds

2020 ◽  
pp. 183-204
Author(s):  
Elena Efremenko ◽  
Il'ya Lyagin

Organophosphorus compounds (OPC) are capable of affecting a wide variety of biological targets, including enzymes. At the same time, there is a large group of enzymes that modify these OPC, mainly by hydrolysis. In total, both those and other enzymes can be involved in determining the content of various OPC. This chapter presents the latest scientific developments in the field of enzyme biosensors for the analysis of OPC in a wide variety of environmental objects. For these purposes, soluble and immobilized forms of enzymes, their various combinations, as well as crude enzymes as a components of microorganisms’ cells can be used. Modern methods make it possible to reach the detection limits of OPC of 10–12 g/L with optical or electrochemical registration of the signal, which opens up enormous prospects for the use of such biosensors in practice. Special examples of commercially available enzyme biosensors for OPC determining are provided.

Author(s):  
Elena Efremenko ◽  
Il'ya Lyagin

Organophosphorus compounds (OPC) are capable of affecting a wide variety of biological targets, including enzymes. At the same time, there is a large group of enzymes that modify these OPC, mainly by hydrolysis. In total, both those and other enzymes can be involved in determining the content of various OPC. This chapter presents the latest scientific developments in the field of enzyme biosensors for the analysis of OPC in a wide variety of environmental objects. For these purposes, soluble and immobilized forms of enzymes, their various combinations, as well as crude enzymes as a components of microorganisms’ cells can be used. Modern methods make it possible to reach the detection limits of OPC of 10–12 g/L with optical or electrochemical registration of the signal, which opens up enormous prospects for the use of such biosensors in practice. Special examples of commercially available enzyme biosensors for OPC determining are provided


2021 ◽  
Vol 22 (4) ◽  
pp. 1761
Author(s):  
Ilya Lyagin ◽  
Elena Efremenko

Organophosphorus compounds (OPCs) are able to interact with various biological targets in living organisms, including enzymes. The binding of OPCs to enzymes does not always lead to negative consequences for the body itself, since there are a lot of natural biocatalysts that can catalyze the chemical transformations of the OPCs via hydrolysis or oxidation/reduction and thereby provide their detoxification. Some of these enzymes, their structural differences and identity, mechanisms, and specificity of catalytic action are discussed in this work, including results of computational modeling. Phylogenetic analysis of these diverse enzymes was specially realized for this review to emphasize a great area for future development(s) and applications.


Author(s):  
Sergey Varfolomeev ◽  
Bella Grigorenko ◽  
Sofya Lushchekina ◽  
Patrick Masson ◽  
Galina Mahaeva ◽  
...  

“Biocleaners” or “bioscavengers” are biological objects (enzymes, catalytic antibodies) that are capable of binding and/or hydrolyzing organophosphorus compounds (OPC). Their use seems to be the most effective alternative to traditional antidotes to neutralize or detoxify OPC. The introduction of bioscavengers allows neutralizing toxicant molecules in the bloodstream before they reach their biological targets, thereby providing protection against poisoning. Bioscavengers of the first-generation neutralized OPC molecules by stoichiometrically binding to them. The safety and efficacy of human butyrylcholinesterase (BChE) for protecting against OPC poisoning has been shown. However, the stoichiometric neutralization of OPC requires the introduction of a huge amount of expensive biopharmaceuticals. Catalytic bioscavengers that hydrolytically neutralize OPC were introduced at a much lower dose to achieve the same degree of effectiveness. The most effective catalytic bioscavengers are enzymes. The most promising enzymes are artificial mammalian paraoxonase mutants and bacterial phosphotriesterases. However, studies of other enzymes, such as prolidases, oxidases, artificial mutants of cholinesterases and carboxyl esterases and catalytic antibodies are actively ongoing. Since OPC are pseudosubstrates of cholinesterases (ChEs), a detailed description of the mechanisms of inhibition, dealkylation, and spontaneous reactivation of phosphorylated ChEs is critical for the development of ChEs mutants with a high rate of hydrolysis of OPC. The review presents an analysis of different views on the mechanisms of interaction of ChEs with OPC, discusses the possible directions of creating effective catalytic biological traps based on BChE and changes in their mechanism of action as compared to the native enzyme. A separate section is devoted to the effect of mutations, both polymorphic and artificial, on the stability of the protein molecule of BChE.


2019 ◽  
Vol 84 (4) ◽  
pp. 19-35 ◽  
Author(s):  
O.V. Fedchenko ◽  
P.G. Zhminko

Objective: analysis and summary of the literature data and own studies on the possibility of using biomarkers of exposure and effect of organophosphorus compounds (OPCs), determination of immunological biomarkers of the effect under exposure to OPCs that cause delayed neurotoxicity (DN). Materials and Methods. Analytical methods were used in the work: collection of scientific information on the topic, analysis of data and scientific summary of the results. Re-assessment of the effect of OPCs causing DN was performed from the perspective of determination of the most informative immunological biomarkers of the effect of known neurotoxicants. Analysis of the study results of the effect of neurotoxic OPCs, triorthocresyl phosphate (TOCP), Afos on the immune system was performed using the most sensitive model — chicken breed Leghorn in isotoxic doses (500 mg/kg and 200 mg/kg, respectively) using common immunotoxicology methods. Results and Conclusions. The article analyses and concludes current literary data on the justified use of biomarkers of exposure and effect of OPCs that are widespread in the environmental objects and are one of the reasons of acute and chronic poisoning in the population. We’ve reviewed aspects of the necessity for implementation of scientifically justified approach to the development and assessment of biomarkers and creation of the unified diagnostic complex that includes biomarkers of exposure, specific and non-specific action, with wider diagnostic abilities compared with determination of isolated parameters that is the basis for diagnostics, efficient treatment and prediction of consequences of poisoning with OPCs. Based on the results of own studies, we proposed the use of some parameters as the immunological biomarkers of the effect of OPCs with DN: the level of finely dispersed circulating immune complexes in the blood serum and the level of anti-brain antibodies, the number and functional activity of blood neutrophils; the number of T-and B-lymphocytes and their functional activity; the number of NK-cells, T-helper cells, and T-suppressors.


Author(s):  
R. N. Plotnikova

The scope of application of the modern regulatory framework in the field of assessing the negative impact on the environment for food industry enterprises has been investigated. The issues of biotechnological protection of environmental objects are considered, taking into account the effective use of natural resources, production and consumption waste. An assessment of modern methods and approaches to environmental health improvement, including minimization of negative impacts, is given. An expert assessment of the environmental component of the business was carried out. It is shown that an effective environmental policy in all areas of business should be accompanied by the disclosure of environmental initiatives in information and communication networks through marketing campaigns. The main approaches to biotechnological protection of environmental objects, aimed at the efficient use of natural resources, production and consumption waste, are analyzed. Modern methods and approaches to environmental health improvement, including minimization of negative impact, are evaluated. The necessity of extraction of toxic heavy metals from waste before their disposal for storage and disposal in order to prevent damage to the environment is shown. The advantages of biochemical soil remediation for leaching metals with selection and specialized adaptation of working strains of microorganisms are noted. The need for large-scale incentives for manufacturers to introduce technological processes that minimally pollutes the environment has been established.


2020 ◽  
pp. 219-230
Author(s):  
Sergey Eremin

Organophosphorus compounds (OP) are found in environmental objects and food products. Due to their high toxicity and inhibition of cholinesterase activity, it is necessary to control residual amounts of OP. The most common methods for determining OP are gas and liquid chromatography with various detection methods. However, chromatographic analysis is lengthy, requires complex sample preparation and expensive equipment, which limits its use for screening a large number of samples and continuous monitoring of the content of OP. To detect the OP, it is necessary to use High Throughput Screening methods, using simple, fast and inexpensive analysis methods. Currently, immunochemical methods are increasingly used to determine OP. These methods are based on the recognition of the analyte (antigen) by specific receptors (antibodies) with the formation of the antigen-antibody complex and the measurement of the analytical signal generated by the immunochemical test system in response to complex formation, which leads to high sensitivity and specificity of the analysis.


2020 ◽  
pp. 233-252
Author(s):  
Elena Efremenko ◽  
Il'ya Lyagin

Organophosphorus compounds (OPC) are able to interact with various biological targets in living organisms, including enzymes. However, the binding of OPC to enzymes does not always lead to negative consequences for the body itself, since there is an extensive group of biocatalysts that can catalyze the chemical transformations of these organophosphorus substrates. Some of these enzymes are discussed in this work.


2020 ◽  
pp. 140-180
Author(s):  
Sergey Varfolomeev ◽  
Bella Grigorenko ◽  
Sofya Lushchekina ◽  
Patrick Masson ◽  
Galina Mahaeva ◽  
...  

“Biocleaners” or “bioscavengers” are biological objects (enzymes, catalytic antibodies) that are capable of binding and/or hydrolyzing organophosphorus compounds (OPC). Their use seems to be the most effective alternative to traditional antidotes to neutralize or detoxify OPC. The introduction of bioscavengers allows neutralizing toxicant molecules in the bloodstream before they reach their biological targets, thereby providing protection against poisoning. Bioscavengers of the first-generation neutralized OPC molecules by stoichiometrically binding to them. The safety and efficacy of human butyrylcholinesterase (BChE) for protecting against OPC poisoning has been shown. However, the stoichiometric neutralization of OPC requires the introduction of a huge amount of expensive biopharmaceuticals. Catalytic bioscavengers that hydrolytically neutralize OPC were introduced at a much lower dose to achieve the same degree of effectiveness. The most effective catalytic bioscavengers are enzymes. The most promising enzymes are artificial mammalian paraoxonase mutants and bacterial phosphotriesterases. However, studies of other enzymes, such as prolidases, oxidases, artificial mutants of cholinesterases and carboxyl esterases and catalytic antibodies are actively ongoing. Since OPC are pseudosubstrates of cholinesterases (ChEs), a detailed description of the mechanisms of inhibition, dealkylation, and spontaneous reactivation of phosphorylated ChEs is critical for the development of ChEs mutants with a high rate of hydrolysis of OPC. The review presents an analysis of different views on the mechanisms of interaction of ChEs with OPC, discusses the possible directions of creating effective catalytic biological traps based on BChE and changes in their mechanism of action as compared to the native enzyme. A separate section is devoted to the effect of mutations, both polymorphic and artificial, on the stability of the protein molecule of BChE.


PEDIATRICS ◽  
1976 ◽  
Vol 58 (5) ◽  
pp. 637-638
Author(s):  
Robert J. Haggerty

In a presidential election year everyone is familiar with opinion polls. Pediatrics has joined the crowd and commissioned a poll to learn the opinions of its readers. In doing this we recognize the many problems associated with polling: questions of reliability and validity; the acknowledgment that polls measure attitudes and not behavior; and, most important, editors—like presidents—should lead and not merely follow opinions. But modern methods of polling are able to determine the beliefs of a large group by asking questions of only a small sample if that sample is scientifically selected. The editors believe that readers' opinions are important in planning the future content of Pediatrics and therefore authorized this poll to provide "detailed information about the reader of the publication and his/her attitude toward Pediatrics, so that decisions can be made for future directions of the publication."


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