Four compounds were prepared: 3-oxo-1-methylquinuclidinium iodide (I), 2-hydroxyiminomethyl-1,3-dimethylimidazolium iodide (II) and two conjugates of I and II linked by -(CH2)3- (III) and -CH2-O-CH2- (IV). The aim was to evaluate separately the properties of I and II as opposed to III and IV, which contain both moieties in the same molecule. All four compounds were reversible inhibitors of acetylcholinesterase (AChE; EC 3.1.1.7). The enzyme/inhibitor dissociation constants for the catalytic site ranged from 0.073 mM (II) to 1.6 mM (I). The dissociation constant of I for the allosteric (substrate inhibition) site was 4.8 mM. Possible binding of the other compounds to the allosteric site could not be measured because II, III and IV reacted with the substrate acetylthiocholine (ATCh) and at high ATCh concentrations the non-enzymic reaction interfered with the enzymic hydrolysis of ATCh. The rate constants for the non-enzymic ATCh hydrolysis were between 23 and 37 l/mol per min. All four compounds protected AChE against phosphorylation by Soman and VX. The protective index (PI) of I (calculated from binding of I to both, catalytic and allosteric sites in AChE) agreed with the measured PI; this confirms that allosteric binding contributes to the decrease of phosphorylation rates. The PI values obtained with III and IV were higher than those predicted by the assumption of their binding to the AChE catalytic site only. The toxicity (i.p. LD50) of compounds I, II, III and IV for mice was 0.21, 0.68, 0.49 and 0.77 mmol/kg body wt. respectively. All four compounds protected mice against Soman when given (i.p.) together with atropine 1 min after Soman (s.c.). One-quarter of the LD50 dose fully protected mice (survival of all animals) against 2.52 (IV), 2.00 (I and III) and 1.58 (II) LD50 doses of Soman.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1007/s002040050504 | DOI Listing |
Structure
January 2025
Department of Chemistry, Emory University, Atlanta, GA 30322, USA. Electronic address:
Thio/selenoimidazole Nπ-methyltransferases are an emerging family of enzymes catalyzing the final step in the production of the S/Se-containing histidine-derived antioxidants ovothiol and ovoselenol. These enzymes, prevalent in prokaryotes, show minimal sequence similarity to other methyltransferases, and the structural determinants of their reactivities remain poorly understood. Herein, we report ligand-bound crystal structures of OvsM from the ovoselenol pathway as well as a member of a previously unknown clade of standalone ovothiol-biosynthetic Nπ-methyltransferases, which we have designated OvoM.
View Article and Find Full Text PDFSci Total Environ
January 2025
Department of Earth Resources & Environmental Engineering, Hanyang University, Seoul 04763, Republic of Korea. Electronic address:
Concentrated animal feeding operation facility in modern livestock industry is pointed out as a point site causing environmental pollution due to massive generation of manure. While livestock manure is conventionally treated through biological processes, composting and anaerobic digestion, these practices pose difficulties in achieving efficient carbon utilization. To address this, this study suggests a pyrolytic valorization of livestock manure, with a focus on enhancing syngas production.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Physics, Alba Nova Research Center, Stockholm University, Stockholm SE-106 91 Sweden.
Iron-doped nickel oxyhydroxides, Ni(Fe)OH, are among the most promising oxygen evolution reaction (OER) electrocatalysts in alkaline environments. Although iron (Fe) significantly enhances the catalytic activity, there is still no clear consensus on whether Fe directly participates in the reaction or merely acts as a promoter. To elucidate the Fe's role, we performed X-ray spectroscopy studies supported by DFT on Ni(Fe)OH electrocatalysts.
View Article and Find Full Text PDFPlants (Basel)
January 2025
Research Center of Buckwheat Industry Technology, College of Life Science, Guizhou Normal University, Guiyang 550025, China.
Tartary buckwheat is a nutrient-rich pseudo-cereal whose starch contents, including amylose and amylopectin contents, and their properties hold significant importance for enhancing yield and quality. The granule-bound starch synthase (GBSS) is a key enzyme responsible for the synthesis of amylose, directly determining the amylose content and amylose-to-amylopectin ratio in crops. Although one has already been cloned, the genes at the genome-wide level have not yet been fully assessed and thoroughly analyzed in Tartary buckwheat.
View Article and Find Full Text PDFPathogens
January 2025
Departamento de Biología, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta s/n, Guanajuato 36050, Mexico.
The path to survival for pathogenic organisms is not straightforward. Pathogens require a set of enzymes for tissue damage generation and to obtain nourishment, as well as a toolbox full of alternatives to bypass host defense mechanisms. Our group has shown that the parasitic protist encodes for 14 sphingomyelinases (SMases); one of them (acid sphingomyelinase 6, aSMase6) is involved in repairing membrane damage and exhibits hemolytic activity.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!