Organophosphates detoxification

Chambers, HW USDA Investigation of the nature of esterases involved in organophosphate detoxification including methyl parathion. 

KIAA1363 in ether lipid metabolism and organophosphate detoxification. Toxicol. Appl. Pharmacol. 228 42-8. 

Furlong, C.E., Costa, L.G., Hassett, C., Richter, R.J., Sundstrom, J.A., Adler, D.A., Disteche, C.M., Omiecinski, C.J., Chapline, C., Crabb, J.W. (1993). Human and rabbit paraoxonases purification, cloning, sequencing, mapping and role of polymorphism in organophosphate detoxification. Chem. Biol. Interact. 87 35-48. 

Nomura, D.K., Fujioka, K., Issa, R.S., Ward, A.M., Cravatt, B.F., Casida, J.E. (2008). Dual roles of brain serine hydrolase KIAA1363 in ether lipid metabolism and organophosphate detoxification. Toxicol. Appl. Pharmacol. 228 42-8. 

Pond, A. L., Chambers, H. W and Chambers, J, E (1995). Organophosphate detoxification potential of various rat tissues via A-c.stcrasc and aliesterase activity, Toxicol Lett, 78, 245-252,... 

There is a second type of cholinesterase called butyrylcholinesterase, pseudocholinesterase, or cholinesterase. This enzyme is present in some nonneural cells in the central and peripheral nervous systems as well as in plasma and serum, the liver, and other organs. Its physiologic function is not known, but is hypothesized to be the hydrolysis of esters ingested from plants (Lefkowitz et al. 1996). Plasma cholinesterases are also inhibited by organophosphate compounds through irreversible binding this binding can act as a detoxification mechanism as it affords some protection to acetylcholinesterase in the nervous system (Parkinson 1996 Taylor 1996). 

Sultatos, L.G. and S.D. Murphy. 1983. Hepatic microsomal detoxification of the organophosphates paraoxon and chlorpyrifos oxon in the mouse. Drug Metabol. Dispos. 11 232-238. 

The inactivation and detoxification of paraoxon and congeners are catalyzed by the so-called A-esterases, which, as discussed, comprise aryleste-rase (sometimes still called paraoxonase, EC 3.1.1.2) and phosphoric triester hydrolases (phosphotriesterases, EC 3.1.8) subdivided into aryldialkylphos-phatase (organophosphate hydrolase, paraoxonase, EC 3.1.8.1) and organophosphorus acid anhydrolases (EC 3.1.8.2 see Sect. 9.3.7) [65][69][106-108], These activities, which occur mostly in the mammalian liver and... 

T. L. Diepgen, M. Geldmacher-von Mallinckrodt, Interethnic Differences in the Detoxification of Organophosphates The Human Serum Paraoxonase Polymorphism , Arch. Toxicol. 1986, Suppl. 9, 154-158. 

Chemical degradation has been investigated by Shlh and Dal Porto Q) and by Lande ( ) under EPA auspices as an alternative approach (to landfill disposal) for the removal of pesticide residues. Among candidate reactions for the safe detoxification of pesticides, only alkaline hydrolysis was recommended. Several organophosphates and carbamates were identified as amenable to a degradation procedure using strong base/aqueous alcohol. The... 

Ghanem E, Raushel EM (2005) Detoxification of organophosphate nerve agents by bacterial phosphotriesterase. Toxicol Appl Pharmacol 207(2, Supplement l) 459-47... 

Structures of some organophosphate cholinesterase inhibitors. The dashed lines indicate the bond that is hydrolyzed in binding to the enzyme. The shaded ester bonds in malathion represent the points of detoxification of the molecule in mammals and birds. 

Havens. P.L. and Rase, H.E. Reusable immobilized enzyme/polyurethane sponge for removal and detoxification of localized organophosphate pesticide spills, Ind. Eng. Chem. Res., (1993) 32. 10, 2254-58. 

Degradation of agrochemicals, solvents, degreasers, flame retardants, and chemical intermediates used in the production of high volume chemicals [113] detoxification of chlorophenols [61] Transformation of pesticides including phenylcarbamates (e.g., CIPC, IPQ and organophosphates (e.g., malathion, paraoxon, parathion) [53]... 

It has been proposed that parathion hydrolase, also known as organophosphorous phosphotriesterase, be used for pesticide detoxification as an alternative to more common treatment methods. Parathion hydrolase is produced by a number of bacteria including Pseudomonas sp., Flavobacte-rium sp. and a recombinant Streptomyces [17,54]. It has been shown to hydrolyze some of the most widely used organophosphate pesticides such as methyl and ethyl parathion, diazinon, fensulfothion, dursban, and couma-phos [18,19]. It should be noted that organophosphate pesticides constitute the major proportion of agricultural pesticides used at present and are implicated in an estimated 800,000 pesticide poisoning cases every year [18]. Hydrolysis accomplishes the detoxification of the pesticide and makes the products amenable to biological treatment. 

Caldwell SR, Raushel FM. Detoxification of organophosphate pesticides using an immobilized phosphotriesterase from Pseudomonas diminuta. Biotechnol Bioeng 1991 37 103-109. 

The well-known selectivities of some organophosphates may be explained by the balance of enzymatic events. The reduced toxicity of the insecticide malathion to mammals is largely the result of rapid activation by desulfuration in the insect and the more rapid detoxificaton by carboxylesterases and glutathione transferases in the mammal (3). Design of new pest bioregulators should exploit enhanced activation and decreased detoxification capabilities in the targeted pests. 

Inhibitors of a herbivore s ability to detoxify plant toxicants may expectedly be more slow-acting than neurotoxicants such as organophosphates. Nevertheless, securance of synergists of dietary toxicants that complement activation reactions and inhibit detoxification reactions in the targeted pests will have potential for IPM, since they should be compatible or moreover, augment plant antibiosis, natural enemies and concurrently used pesticides. 

O-Dealkylation O-Dealkylation of alkyl groups of the ester or ether structures of insecticides occurs frequently, but it also involves an unstable a-hydroxy intermediate as found in N-dealkylation. For example, methoxychlor is O-demethylated by the system (Figure 8.6). O-Dealkylation is known to occur with a wide variety of organophosphates, including certain dimethyl triesters. O-Dealkylation results in detoxification. 

In certain situations it is possible to overcome herbicide metabolism-based resistance by adding an ingredient that will block detoxification of the herbicide in the resistant weed. One example is with propanil-resistant Echinochloa colona in rice in Latin America. The addition of piperophos, an organophosphate insecticide that inhibits the aryl acylamidase activity that confers resistance on the weed biotype [11]. This combination, based on an undo standing of the resistance mechanism, has beat approved for use on resistant... 

Gordon, R., Baker, K., Askins, L., Ratcliffe, R., Lindsay, D., Owens, R. et al. (2006). Chemical warfare agents (organophosphates and vesicant) and biological decontamination and detoxification using polyurethane sponges. Toxicologist 9fS 393. 

Saxena, A., Maxwell, D.M., Quinn, D.M., Radic, Z., Taylor, P., Doctor, B.P. (1997a). Mutant acetylcholinesterases as potential detoxification agents for organophosphate poisoning. Biochem. Pharmacol. 54 269-74. 

The term A-esterase originally referred to an enzyme(s) in the serum that metabolized carboxylic esters and was insensitive to inhibition by organo-phosphates (in contrast to the B-esterases, which are inhibited by organophosphates). Later this activity was shown to be associated with the detoxification of paraoxon, leading to the use of the term A-esterase to... 

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