Schallreuter, Karin U.Gibbons, Nick C.Elwary, Souna M.A.Parkin, Susan M.Wood, John M.2009-05-262009-05-262007Schallreuter KU, Gibbons NC, Elwary SM, Parkin SM and Wood JM (2007) Calcium-activated butyrylcholinesterase in human skin protect acetylcholinesterase against suicide inhibition by neurotoxic organophosphates. Biochemical and Biophysical Research Communications. 355(4): 1069-1074.http://hdl.handle.net/10454/2691NoThe 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 (0.5 × 10-3 M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. 45Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H2O2-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 1.8 m2 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 tissueenHuman epidermisHydrogen peroxideAcetylcholinesteraseCalciumEF-handOrganophosphatesButyrylcholinesteraseArticlehttps://doi.org/10.1016/j.bbrc.2007.02.078