Correlation between butyrylcholinesterase variants and sensitivity to soman toxicity.

Abstract

Butyrylcholinesterase (BChE) is synthesized in the liver and found in high concentrations in blood plasma, liver, heart, pancreas, vascular endothelium, skin, brain white matter, smooth muscle cells and adipocytes. BChE is a non specific enzyme that hydrolyzes different choline esters (succinylcholine, mivacurium) and many other drugs such as aspirin, cocaine and procaine. The enzyme is also considered as a bioscavenger due to its ability to neutralize the toxic effects of organophosphorus compounds (nervous system fs agents) such as soman. BChE displays several polymorphisms that influence its serum activity; therefore they could determine the individual sensitivity to chemical nerve agents. In this study, we investigated the correlation between BChE variants and the degree of enzyme inhibition and reactivation after soman application on blood samples of 726 individuals. The blood samples of individuals expressing abnormal variants, were more sensitive to soman compared to variants of homozygotes and heterozygotes for U-allele. We found significant differences in the degree of enzyme reactivation between different variants (with and without U-presence).

Redox-Controlled Fluorescent Nanoswitch Based on Reversible Disulfide and Its Application in Butyrylcholinesterase Activity Assay

“…Table lists the measured values of BChE level in three human serum samples based on our method and Ellman method, and the reported normal BChE level in large population. It is found that the average value of measured BChE level (8574.2 ± 8.7 U/L) from our method is very close to that (8827.2 ± 20.6 U/L) obtained based on the Ellman method, and both of them fall in the normal range of healthy people (9010.0 ± 2041), and this good agreement is convincing that our assay is capable of accurately measuring BChE level in real human serum.…”

“…BChE levels of the three serum samples were also measured using traditional Ellman method for comparison. method, and both of them fall in the normal range of healthy people (9010.0 ± 2041), 39 and this good agreement is convincing that our assay is capable of accurately measuring BChE level in real human serum.…”

Las enzimas involucradas en el metabolismo de la cocaína: Una nueva aproximación farmacológica para el tratamiento de la intoxicación por sobredosis de cocaína

“…35,36 Los niveles normales de BChE varían entre los individuos y son dependientes de la edad, el estado de salud, la exposición a toxinas ambientales y a factores genéticos. [37][38][39] Algunos reportes clínicos indican que los individuos que sufren de graves problemas médicos después del uso de la cocaína, tienden a mostrar una menor actividad en la BChE plasmática que aquellos que experimentan problemas menos severos. [40][41][42] Adicionalmente, algunos estudios genéticos han reportado que en casos extremos de intoxicación con cocaína, los pacientes homocigotos muestran, o bien una variante "silente" de la BChE, la cual no expresa actividad catalítica detectable, 43,44 o bien niveles bajos de expresión de la BChE, o incluso muestran variantes defectuosas o "atípicas" de la enzima.…”

Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors

“…Carbamate-inhibited BChE spontaneously regains full activity with a half-life of about 2–3 h. , Organophosphorus nerve agents, having lost the leaving group during coupling to serine, lose a second group in a process called aging. The rate of aging is fast for soman (half-life 2 min) and relatively slow for sarin (half-life of 6 h) bound to wild-type BChE. , Soman-inhibited atypical BChE regained 16%, whereas soman-inhibited wild-type BChE regained 7% of its original activity following incubation with HI-6 oxime . This result can be interpreted to mean that soman bound to atypical BChE ages more slowly.…”

“… 63 , 64 Soman-inhibited atypical BChE regained 16%, whereas soman-inhibited wild-type BChE regained 7% of its original activity following incubation with HI-6 oxime. 65 This result can be interpreted to mean that soman bound to atypical BChE ages more slowly. A parallel study for soman-inhibited human AChE showed that the D74N mutant, homologous to atypical BChE, aged 15-fold more slowly than soman-inhibited wild-type AChE.…”