Kinetic analyses of the microsomal biotransformation of the phosphorothioate insecticides chlorpyrifos and parathion

Lester G. Sultatos, Sheldon D. Murphy

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Kinetic Analyses of the Microsomal Biotransformation of the Phosphorothioate Insecticides Chlorphyrifos and Parathion. Sultatos, L.G. and Murphy, S.D. (1983). Fundam. and Appl. Toxicol. 3:16-21. Chlorpyrifos [0,0-diethyl-0-(3,5,6-trichloro-2-pyridyl) phosphorothioate] was metabolized to chlorpyrifos oxon [0,0-diethyl-0-(3,5,6-trichloro-2-pyridyl) phosphate] and to 3,5,6-trichloro-2-pyridinol by mouse hepatic microsomes. Formation of both chlorpyrifos oxon and 3,5,6-trichloro-2-pyridinol required NADPH, and was inhibited by carbon monoxide. Kinetic analyses using direct linear plots determined the appKm's for formation of chlorpyrifos oxon and 3,5,6-trichloro-2-pyridinol to be 20.9 ± 3.3 μM and 16.1 ± 3.4 μM respectively, while the appVmax's for the same reactions were 3.9 ± 0.2 nmols/100 mg liver/min and 8.1 ± 0.3 nmols/100 mg liver/min respectively. Incubation of parathion [0,0-diethyl-0-(4-nitrophenyl) phosphorothioate] with mouse hepatic microsomes produced paraoxon [0,0-diethyl-0-(4-nitrophenyl) phosphate] and p-nitrophenol. The appKm's for the formation of paraoxon and p-nitrophenol were 29.6 ± 4.2 μM and 26.5 ± 3.8 μM respectively, with appVmax's of 5.8 ± 0.6 nmols/100 mg liver/min and 6.7 ± 0.5 nmols/100 mg liver/min, respectively. Incubation of both parathion and chlorpyrifos at various concentrations with mouse hepatic microsomes resulted in inhibition of production of paraoxon, p-nitrophenol, chlorpyrifos oxon, and 3,5,6-trichloro-2-pyridinol, which was characteristic of mixed type inhibition. This complex kinetic behavior could arise as a result of competitive interactions of parathion and chlorpyrifos with multiple forms of microsomal cytochrome P-450.

Original languageEnglish (US)
Pages (from-to)16-21
Number of pages6
JournalToxicological Sciences
Issue number1
StatePublished - Jan 1983
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Toxicology


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