Oximes enzyme interactions

Reactivation of the inhibited enzyme is effected by a nucleophilic oxime, which also contains a cationic quaternary centre to promote coulombic interaction with the anionic site of the enzyme. Oxime reactivators act by nucleophilic reaction at the phosphorus atom to form a phosphylated oxime, with displacement of the regenerated enzyme as illustrated by equation 50. 

Over the last 30 years an ever increasing amount of information on the biosynthesis of oxime intermediates in plant metabolism and on interactions of oximes with enzymes has accumulated. Enzymatic reactions that were characterized with respect to oximes as products, substrates or inhibitors are listed in Table 2. 

Interactive models, which have been developed and validated, exist for countermeasures which compete with NA inhibition of ChE or the regeneration of the free enzyme from its inhibited state, such as pyridostigmine and oximes, respectively. Numerous data in the literature describe the kinetics of interaction between nerve agents and other OPs and specific countermeasures at active enzyme sites of eoncem. For example, Davies and Green (1956) have measured the rate of reactivation of inhibited erythrocyte... 

Ability of oximes to interact directly with some OPC [58] and also with phosphorylated enzyme [59] is considered as an additional protective mechanism of their action. A value of the reaction indicated for the organism depends upon subsequent fate of the phosphorylated oxime. The formation of less toxic products in case of fast degradation of the phosphorylated oxime is evaluated as the process of OPC detoxication [60], while amplification of the poisoning enzyme toxicity is accompanied with the formation of strong phosphorylated oxime [61], That is the reason why prophylactic use of oximes in the last case can result in the reverse effect. 

Generally, the reactivating efficacy of oximes depends on their reactivity and affinity for OPC-inhibited enzyme. Their reactivity is derived from the nucleic activity of oxime anion that is bound on the pyridinium ring (8). Oximes differ from each other by the position of the oxime group on the pyridinium ring only. The reactivity of all available oximes is almost the same because their basic structure is very similar (8). The affinity of oximes for intact enzyme, characterized by dissociation constant of enzyme-reactivator complex (Kdls), and for nerve agent-inhibited enzyme, characterized by dissociation constant of inhibited enzyme-reactivator complex (Kr), is determined by various physicochemical factors such as steric compatibility, electrostatic effects, hydrophobic interactions and by the shape and the size of the whole molecule as well as functional groups (22). 

First, carbamoylation, the interaction between carbamates and the active site of AChE, is freely and spontaneously reversible, unlike the normally irreversible inhibition of AChE by the nerve agents. No oxime reactivators are needed to dissociate, or decarbamoylate, the enzyme from a carbamate compound. Carbamates do not undergo the aging reaction of nerve agents bound to AChE. 

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