Enzymes for detoxification of organophosphorus compounds: diversity and functions

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.


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.



2020 ◽  
Vol 9 (4) ◽  
pp. 40-43
Author(s):  
N. K. Yuldasheva ◽  
S. D. Gusakova ◽  
D. Kh. Nurullaeva ◽  
N. T. Farmanova ◽  
R. P. Zakirova ◽  
...  

Introduction. Lipids are a widespread group of biologically active substances in nature, making up the bulk of the organic substances of all living organisms. They accumulate in plants in seeds, as well as in fruits and perform a number of vital functions: they are the main components of cell membranes and the energy reserve for the body.Aim. Study of neutral lipids of sown oats (Avena sativa L.).Materials and methods. The objects of the study were fruits (grains) of oats of the sown variety "Tashkent 1," harvested in the Republic of Uzbekistan. Results and discussions. Neutral lipids of oat grains have been found to contain 13 fatty acids with a predominance of the sum of oleic, linolenic and linoleic acids. The total degree of unsaturation was almost 78%. Absorption bands characteristic of these substances were observed in the IR spectrum of MEGC.Conclusion. According to the results of the NL analysis, oat grains consisted of triacylglycerides and free LCDs, which were accompanied by hydrocarbons, phytosterols, triterpenoids and tocopherols.



2019 ◽  
Vol 05 ◽  
Author(s):  
Atul Sharma ◽  
Devender Pathak

Keeping this fact that study of a body is biology but life is all about chemicals and chemical transformations, many medicinal chemist start research in finding new and novel chemical compounds which having pharmacological activities. Most of those chemical compounds which are having active pharmacological effects are heterocyclic compounds. Heterocyclic compounds clutch a particular place among pharmaceutically active natural and synthetic compounds. The ability to serve both as biomimetics and reactive pharmacophores of heterocyclic nuclei is incredible and it has principally contributed to their unique value as traditional key elements of numerous drugs. These heterocyclic nuclei offer a huge area for new lead molecules for drug discovery and for generation of activity relationships with biological targets to enhance pharmacological effects. For these reasons, it is not surprising that this structural class has received special attention in drug discovery. The hydrogen bond acceptors and donors arranged in a manner of a semi-rigid skeleton in heterocyclic rings and therefore they can present a varied display of significant pharmacophores. Lead identification and optimization of drug target probable can be achieved by generation of chemical diversity produced by derivatization of heterocyclic pharmacophores with different groups or substituents. A tricyclic carbazole nucleus is an integral part of naturally occurring alkaloids and synthetic derivatives, possessing various potential biological activities such as anticancer, antimicrobial and antiviral. Binding mechanism of carbazole with target receptor as a molecule or fused molecule exhibits the potential lethal effect.



2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Krishna Kanta Ghosh ◽  
Parasuraman Padmanabhan ◽  
Chang-Tong Yang ◽  
Sachin Mishra ◽  
Christer Halldin ◽  
...  

Abstract Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria. PET radiotracers usually encounter different chemical modifications including redox reaction, hydrolysis, decarboxylation, and various conjugation processes within living organisms. Due to this biotransformation, different chemical entities are produced, and the amount of the parent radiotracer is declined. Consequently, the signal measured by the PET scanner indicates the entire amount of radioactivity deposited in the tissue; however, it does not offer any indication about the chemical disposition of the parent radiotracer itself. From a radiopharmaceutical perspective, it is necessary to quantify the parent radiotracer’s fraction present in the tissue. Hence, the identification of radiometabolites of the radiotracers is vital for PET imaging. There are mainly two reasons for the chemical identification of PET radiometabolites: firstly, to determine the amount of parent radiotracers in plasma, and secondly, to rule out (if a radiometabolite enters the brain) or correct any radiometabolite accumulation in peripheral tissue. Besides, radiometabolite formations of the tracer might be of concern for the PET study, as the radiometabolic products may display considerably contrasting distribution patterns inside the body when compared with the radiotracer itself. Therefore, necessary information is needed about these biochemical transformations to understand the distribution of radioactivity throughout the body. Various published review articles on PET radiometabolites mainly focus on the sample preparation techniques and recently available technology to improve the radiometabolite analysis process. This article essentially summarizes the chemical and structural identity of the radiometabolites of various radiotracers including [11C]PBB3, [11C]flumazenil, [18F]FEPE2I, [11C]PBR28, [11C]MADAM, and (+)[18F]flubatine. Besides, the importance of radiometabolite analysis in PET imaging is also briefly summarized. Moreover, this review also highlights how a slight chemical modification could reduce the formation of radiometabolites, which could interfere with the results of PET imaging. Graphical abstract



2011 ◽  
Vol 47 (3) ◽  
pp. 151-160 ◽  
Author(s):  
Jennifer L. McCown ◽  
Andrew J. Specht

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.



2021 ◽  
Vol 28 ◽  
Author(s):  
Carina Cassini ◽  
Pedro Henrique Zatti ◽  
Valéria Weiss Angeli ◽  
Catia Santos Branco ◽  
Mirian Salvador

: Phenolic compounds (PC) have many health benefits such as antioxidant, anticarcinogenic, neuroprotective, and anti-inflammatory activities. All of these activities depend on their chemical structures and their interaction with biological targets in the body. PC occur naturally in polymerized form, linked to glycosides and requires metabolic transformation from their ingestion to their absorption. The gut microbiota can transform PC into more easily absorbed metabolites. The PC, in turn, have prebiotic and antimicrobial actions on the microbiota. Despite this, their low oral bioavailability still compromises biological performance. Therefore, the use of nanocarriers has been demonstrated to be a useful strategy to improve PC absorption and, consequently, their health effects. Nanotechnology is an excellent alternative able to overcome the limits of oral bioavailability of PC, since it offers protection from degradation during their passage through the gastrointestinal tract. Moreover, nanotechnology is also capable of promoting controlled PC release and modulating the interaction between PC and the microbiota. However, little is known about the impact of the nanotechnology on PC effects on the gut microbiota. This review highlights the use of nanotechnology for PC delivery on gut microbiota, focusing on the ability of such formulations to enhance oral bioavailability by applying nanocarriers (polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles). In addition, the effects of free and nanocarried PC or nanocarriers per se on gut microbiota are also described.



2017 ◽  
Vol 119 (9) ◽  
pp. 1-38
Author(s):  
Kyunghwa Lee

Background Although concerns about unintended negative consequences of standards-based accountability (SBA) reform for children's socioemotional development have been raised, few studies have systematically examined early childhood teachers’ perceptions of and practices for children's behavior and bodies under such policy. This study was conducted against the backdrop of the intersection of the accountability policy and the increasing prevalence of Attention Deficit/Hyperactivity Disorder (ADHD) among children, including preschoolers. Purpose The study investigated how early childhood teachers’ perspectives of and practices for the behavior and bodies of children considered at risk of being identified with ADHD later in schooling were related to the increasing concern over school readiness under SBA reform. Research Design Data for a qualitative case study were generated through multiple methods, including video-recorded observations in two African-American children's pre-kindergarten and kindergarten classrooms, interviews with their teachers, and artifact collection. Results The focal children's teachers appropriated the authoritative discourses of ADHD and readiness for school to perceive the children's bodies as uncontrollable and unready for school. The teachers taught the children a variety of bodily techniques to enculturate them in public school and to develop docile student bodies. Keeping their authoritative practices intact, the teachers hardly incorporated the children's areas of strengths into the curriculum and instruction. School was introduced to the children as a carnivalesqueless place, and both SBA reform and ADHD contributed to disembodiment in the public early childhood education settings. Conclusions This study suggests the need for reframing the notion of school readiness; bringing teachers’ folk theories about children's behavior and bodies to their critical awareness; and intentionally balancing serious, rigid parts of the daily classroom routine with relaxed, pleasurable moments.



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.



Author(s):  
Rex Ferguson

DNA profiling, in which individual being is identified by its cellular structures, was first developed by the geneticist Alec Jeffreys in the 1980s. That this source of identity also forms the instructions through which living organisms are generated has complicated profiling’s place in the cultural imaginary of the late twentieth century. So, while profiling actually deals only in non-coding regions of the genome—matter often referred to as ‘junk DNA’—the significance of DNA as a substance of forensic analysis, in the late twentieth century imaginary, is its resonance as the apparent blueprint of existence. The notable features that this blurring of concepts brings about include a conceptualization of identity as a mass of information; notions to do with codes and coding; the presence of the body in the fluids which spill beyond its bounds; and a sense of the body as an archive of heredity and primitivism. In writing specifically about genetic research, Richard Powers’s The Gold Bug Variations (1991) serves a dual function in this chapter, as both an explicatory document and thematic example. But the more substantive analysis is reserved for the work of J. G. Ballard which, from its science fiction origins in novels such as The Drowned World (1962), through the controversial era of Crash (1973), to its trilogy of autobiographical texts (Empire of the Sun (1984), The Kindness of Women (1991), and Miracles of Life (2008)) articulates a form of identity that has close, though often oblique, affinities with all the most prominent features of DNA profiling.



Author(s):  
Noretta koertge

“Chemistry has a position in the center of the sciences, bordering onto physics, which provides its theoretical foundation, on one side, and onto biology on the other, living organisms being the most complex of all chemical systems” (Malmström et al.). Thus begins a recent essay on the development of modern chemistry. Philosophers have long wrestled with how best to describe the exact relationship between chemistry and physics. Is it an example of a classic reduction? But before we ask whether chemistry could in principle be derived from physics, there is a prior question: How well integrated is the science of chemistry itself? This chapter argues that although there is a coherent explanatory core within chemical theory, contingency plays a larger role than is usually recognized. Furthermore, these phenomena at the boundaries of traditional chemistry education are where some of the most important current research is occurring. I will first adopt a quasi-historical approach in this essay, including anecdotes from my own educational trajectory. I then briefly discuss how our current understanding of the explanatory structure of chemistry should be reflected in education today. The professor of quantum chemistry at the University of Illinois in the 1950s told us a story from his PhD defense. His director, Linus Pauling, walked into the room and said something to this effect: “Well, Karplus, you’ve done a bunch of calculations on the hydrogen molecule ion (H2 +). Very nice. But you claim to be a chemist. So please write the Periodic Table on the board for us.” Who knows exactly what point Pauling was actually trying to make, but it reminds us of this basic point. The periodic table with its horizontal and vertical trends is still the basis of the classification of enormous amounts of information about the formulae and properties of chemical compounds. Mendeleev would not have understood talk of strontium-90, but he would have realized immediately that this product of nuclear testing would enter the body in a manner similar to calcium.



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