Interaction between substrates suggests a relationship between organophosphorus-sensitive phenylvalerate- and acetylcholine-hydrolyzing activities in chicken brain.

Abstract

Organophosphorus compounds (OPs) induce neurotoxic disorders through interactions with well-known target esterases, such as acetylcholinesterase and neuropathy target esterase (NTE). However, OPs interact with other esterases of unknown biological function. In soluble chicken brain fractions, three components of enzymatic phenylvalerate esterase activity (PVase) called Eα, Eβ and Eγ, have been kinetically discriminated. These components are studied in this work for the relationship with acetylcholine-hydrolyzing activity. When Eα PVase activity (resistant PVase activity to 1500 μM PMSF for 30 min) was tested with different acetylthiocholine concentrations, inhibition was observed. The best-fitting model to the data was the non-competitive inhibition model (Km=0.12, 0.22 mM, Ki=6.6, 7.6 mM). Resistant acetylthiocholine-hydrolyzing activity to 1500 μM PMSF was inhibited by phenylvalerate showing competitive inhibition (Km=0.09, 0.11 mM; Ki=1.7, 2.2 mM). Eβ PVase activity (resistant PVase activity to 25 μM mipafox for 30 min) was not affected by the presence of acetylthiocholine, while resistant acetylthiocholine-hydrolyzing activity to 25 μM mipafox showed competitive inhibition in the presence of phenylvalerate (Km=0.05, 0.06 mM; Ki=0.44, 0.58 mM). The interactions observed between the substrates of AChE and PVase suggest that part of PVase activity might be a protein with acetylthiocholine-hydrolyzing activity.

• Authors: Mónica Benabent, Eugenio Vilanova, Iris Mangas, Miguel Ángel Sogorb, Jorge Estévez
• Journal: Toxicology letters (Toxicol Lett) Vol. 230 Issue 2 Pg. 132-8 (Oct 15 2014) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 24576786 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Organophosphorus Compounds
• Valerates
• Isoflurophate
• phenyl valerate
• mipafox
• Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide
• Phenylmethylsulfonyl Fluoride
• Carboxylic Ester Hydrolases
• neurotoxic esterase
• Acetylcholinesterase
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Acetylcholinesterase (metabolism)
• Animals
• Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide (pharmacology)
• Brain (enzymology)
• Carboxylic Ester Hydrolases (metabolism)
• Chickens
• Hydrolysis
• Isoflurophate (analogs & derivatives, pharmacology)
• Organophosphorus Compounds (pharmacology)
• Phenylmethylsulfonyl Fluoride (pharmacology)
• Valerates (pharmacology)