Year: 2026
Type: article
Abstract: Aldicarb is a carbamate pesticide used for pest control in agriculture. As a fast-acting acetylcholinesterase inhibitor, aldicarb interferes with the nervous system by preventing the breakdown of acetylcholine. Aldicarb could be used as a chemical-warfare agent to cause mass casualty incidents. There is no specific FDA-approved medication for aldicarb detoxification. Our previous study revealed that an Fc-fused butyrylcholinesterase (BChE) mutant, known as CocH3-Fc(M3), can be inhibited rapidly by aldicarb and that the aldicarb-inhibited enzyme CocH3-Fc(M3) can be reactivated spontaneously, suggesting that CocH3-Fc(M3) may hydrolyze aldicarb. However, the suggested CocH3-Fc(M3)-catalyzed hydrolysis of aldicarb was not confirmed experimentally in the previous study. In the present study, by developing an LC-MS/MS method to detect and quantify aldicarb and aldicarb oxime concentrations, we were able to directly observe the CocH3-Fc(M3)-catalyzed aldicarb hydrolysis for the first time, confirming that CocH3-Fc(M3) indeed has the desirable catalytic activity for aldicarb hydrolysis and may be considered as the first aldicarb hydrolase identified so far. Further, we carried out Michaelis-Menten kinetic analysis on the CocH3-Fc(M3)-catalyzed aldicarb hydrolysis and determined the catalytic parameters (kcat = 0.060 min-1, KM = 2.5 μM, and kcat/KM = 2.4 × 104 min-1 M-1) at 37°C. The obtained kinetic parameters at 37°C will be valuable for further in vivo studies and translational research using CocH3-Fc(M3) and for designing more potent enzymes to hydrolyze aldicarb in the future. Additionally, the LC-MS/MS method developed in this study may serve as a valuable tool to accurately detect aldicarb and its reaction products in future food and environmental safety control efforts and aldicarb-related toxicology studies.
Source: Bioscience Reports
DOI: 10.1042/bsr20254091
Institution: University of Kentucky
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,960
Awards: Development of Long-acting Cocaine Hydrolase as a Treatment for Cocaine Abuse, Long-acting aldicarb hydrolase as a medical countermeasure for aldicarb poisoning, Ghrelin Deacylase as a Treatment for Opioid Polysubstance Abuse, Validation of ghrelin hydrolysis as an effective approach to treatment of substance use disorders, Redesign of Butyrylcholinesterase for Cocaine Metabolism, G9000057706, G9000059500, G9000091403, G9000110450, G9000110678, G9000223770, G9000280494, G9000344026, Long-acting aldicarb hydrolase as a medical countermeasure for aldicarb poisoning
OpenAlex ID: W7130660668
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