Title : Reversible inhibition can profoundly mislead studies on progressive inhibition of enzymes: the interaction of paraoxon with soluble neuropathy target esterase - Barril_1997_Chem.Biol.Interact_108_19 |
Author(s) : Barril J , Vilanova E |
Ref : Chemico-Biological Interactions , 108 :19 , 1997 |
Abstract :
Neuropathy target esterase (NTE) is suggested to be the molecular target for the initiation of the organophosphorus induced delayed polyneuropathy (OPIDP). O,O'-diethyl p-nitrophenyl phosphate (paraoxon) was the non-neurotoxic OP of choice for the standard assay of NTE to block the non-relevant esterases (phenylvalerate hydrolases) because it was supposed not to inhibit the enzymic activity of the target protein while N,N'-diisopropyl phosphorodiamidofluoridate (mipafox) is the neuropathic OP used to inhibit (and so to detect) NTE activity. A soluble form of NTE (S-NTE) had previously been described in peripheral nerve which showed a different inhibitor response from that of the particulate NTE (P-NTE). The use of a sequential type of inhibition protocol revealed the presence of an activity component within S-NTE which was extremely sensitive to different esterase inhibitors. Such a soluble activity component remained hidden under the usual concurrent inhibition procedure with paraoxon and was about one order of magnitude more sensitive than P-NTE to the inhibitors studied in the present article. Our results suggest that paraoxon could produce a strong reversible effect on S-NTE when the concurrent procedure is used so that it interferes with its inhibition by both neuropathy inducers and promoters. As a result S-NTE seems to be much more sensitive, than previously believed, to several esterase inhibitors involved in either the genesis of delayed polyneuropathy and/or axonopathy promotion. |
PubMedSearch : Barril_1997_Chem.Biol.Interact_108_19 |
PubMedID: 9463518 |
Substrate | Phenylvalerate |
Barril J, Vilanova E (1997)
Reversible inhibition can profoundly mislead studies on progressive inhibition of enzymes: the interaction of paraoxon with soluble neuropathy target esterase
Chemico-Biological Interactions
108 :19
Barril J, Vilanova E (1997)
Chemico-Biological Interactions
108 :19