Paraoxon structure

In the body, parathion is converted to paraoxon (structure in Figure 18.8), which is a potent inhibitor of acetylcholinesterase. Because this conversion is required for parathion to have a toxic effect, symptoms develop several hours after exposure, whereas the toxic effects of TEPP or... 

Ileperuma NR, Marshall SDG, Squire CJ, Baker HM, Oakeshott JG, Russell RJ, Plummer KM, Newcomb RD, Baker EN (2007) High-resolution crystal structure of plant carboxyesterase AeCXEl, from Actinidia eriantha, and its complex with a high-affinity inhibitor paraoxon. Biochemistry 46 1851-1859... 

Fig. 31 The structures for parathion (left), paraoxon (middle), and sarin (right).

Structures of several common substrates and an inhibitor used to study the mechanisms of OPA anhydrase activity. DFP (diisopropylfluorophosphate), mipafox (N,N -diisopropylphosphorodi-amidofluoridate), tabun (N,N-dimethylethylphosphoroamidocyanidate), soman(0-l,2,2-trimethylpropylmethylphosphonofluoridate, paraoxon (diethyl 4-nitrophenyl phosphate), and parathion. 

Fig. 1. Structures of the immobilized ligands used for cholinesterase recognition BZE-DADOO, paraoxon-aminohexanol, paraoxon-hexahistidine-Ni2+-NTA-lysine, propidium (from top), each bound to MUAon gold.

OP insecticide with a structure similar to malathion, which is not a substrate for PON (Li et aL, 2000). As also predicted, PON mice showed a dramatically increased sensitivity to chiorpyrifos-oxon and diazoxon (Shih et ai., 1998 Li et ai, 2000). PONl mice showed an intermediate sensitivity to diazoxon toxicity (Li ef al, 2000). PONl null mice showed only a slight increase in sensitivity to the toxicity of chlorpyrifos and diazinon (Shih et a ., 1998 Li el al., 2000). The most surprising observation was that PONl null mice did not show an increased sensitivity to paraoxon, the substrate after which the enzyme was named, despite having no paraoxonase activity in plasma and liver (Li ei ai. 2000). 

The phosphorothioates and phosphorodithioates, shown in Table 1 of Chapter 2, were developed when the nerve agents were found to be too toxic and volatile for use in agriculture. These OP insecticides contain a P-S-alkyl and/ or a P=S group in their structure. The best known member of this class is parathion, the most widely used insecticide at one time and responsible for more cases of accidental poisoning and death than any other OP compound. The activation and conversion of this weak AChEI (parathion) to the more active and potent form (paraoxon) was demonstrated to lake place in the liver (Diggle and Gage, 1951 Gage, 1953). 

Using phantom as a tissue mimicking structure, ultrasound backscattering capacity of gold nanoparticles-loaded lysozyme microbubbles (Fig. 2.12) was demonstrated. In addition, alkaline phosphate conjugated lysozyme microbubbles were shown to possess biosensing capabilities to detect small quantities of paraoxon. 

Paraoxonase/arylesterase from human serum and other manunalian species catalyzes the hydrolysis of organophosphates, aromatic carboxylic acids and possibly carbamates (Primo-Parmo et al. 1996). Paraoxonase (PONl) is so called because paraoxon is the substrate commonly used to measure its enzyme activity (Mackness et al. 1998). The crystal structure of PONl family of calcium-containing... 

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