Boeck_2002_Biochem.Pharmacol_63_2101

Reference

Title : DNA sequence of butyrylcholinesterase from the rat: expression of the protein and characterization of the properties of rat butyrylcholinesterase - Boeck_2002_Biochem.Pharmacol_63_2101
Author(s) : Boeck AT , Schopfer LM , Lockridge O
Ref : Biochemical Pharmacology , 63 :2101 , 2002
Abstract :

The rat is the model animal for toxicity studies. Butyrylcholinesterase (BChE), being sensitive to inhibition by some organophosphorus and carbamate pesticides, is a biomarker of toxic exposure. The goal of this work was to characterize the purified rat BChE enzyme. The cDNA sequence showed eight amino acid differences between the active site gorge of rat and human BChE, six clustered around the acyl binding pocket and two below the active site serine. A prominent difference in rat was the substitution of arginine for leucine at position 286 in the acyl pocket. Wild-type rat BChE, the mutant R286L, wild-type human BChE, and the mutant L286R were expressed in CHO cells and purified. Arg286 was found responsible for the resistance of rat BChE to inhibition by Triton X-100. Replacement of Arg286 with leucine caused the affinity for Triton X-100 to increase 20-fold, making it as sensitive as human BChE to inhibition by Triton X-100. Wild-type rat BChE had an 8- to 9-fold higher K(m) for the positively charged substrates butyrylthiocholine, acetylthiocholine, propionylthiocholine, benzoylcholine, and cocaine compared with wild-type human BChE. Wild-type rat BChE catalyzed turnover 2- to 7-fold more rapidly than human BChE, showing the highest turnover with propionylthiocholine (201,000 min(-1)). Human BChE does not reactivate spontaneously after inhibition by echothiophate, but rat BChE reactivates with a half-life of 4.3hr. Human serum contains 5mg/L of BChE and 0.01mg/L of AChE. Male rat serum contains 0.2mg/L of BChE and approximately 0.2mg/L of AChE.

PubMedSearch : Boeck_2002_Biochem.Pharmacol_63_2101
PubMedID: 12110369
Gene_locus related to this paper: ratno-BCHE

Related information

Mutation L286R_human-BCHE    R286L_ratno-BCHE
Gene_locus ratno-BCHE

Citations formats

Boeck AT, Schopfer LM, Lockridge O (2002)
DNA sequence of butyrylcholinesterase from the rat: expression of the protein and characterization of the properties of rat butyrylcholinesterase
Biochemical Pharmacology 63 :2101

Boeck AT, Schopfer LM, Lockridge O (2002)
Biochemical Pharmacology 63 :2101