Citation

Schallreuter KU, Gibbons NCJ, Elwary SM, Parkin SM, Wood JM. Biochem. Biophys. Res. Commun. 2007; 355(4): 1069-1074.

Copyright

(Copyright © 2007, Academic Press)

DOI

10.1016/j.bbrc.2007.02.078

PMID

17335779

Abstract

The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5x10(-3)M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. (45)Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H(2)O(2)-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8m(2) surface area with its calcium gradient in the 10(-3)M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue.

Language: en

Keywords

Acetylcholinesterase; Amino Acid Sequence; Binding Sites; Butyrylcholinesterase; Calcium; Cholinesterase Inhibitors; Computer Simulation; EF Hand Motifs; Enzyme Activation; Humans; Hydrogen Peroxide; Hydrolysis; Models, Molecular; Neurotoxins; Organophosphates; Oxidation-Reduction; Protein Binding; Protein Structure, Tertiary; Protein Subunits; Skin