Catalytic Efficiency, the Key to Understanding the Ability of PON1 to Protect Against OP Exposure
The next slide provides an explanation for the results seen when the PON1 deficient mice are injected with either purified human PON1-192 alloform (PON1-Q192 or PON1-R192) or saline and exposed dermally to the indicated organophosphates (chlorpyrifos oxon, diazoxon and paraoxon).
PON1-192 alloforms (Q102 or R192) were purified from human plasma from PON1 Status-typed individual human plasma samples. The purified PON1 was injected into the PON1 deficient mice to determine the effectiveness of each alloform to protect against exposure to chlorpyrifos oxon, diazoxon and paraoxon. The degree of protection provided by each alloform was closely related to the catalytic efficiency of the specific alloform for the given OP. PON1-R192 provided better protection against chlorpyrifos oxon exposure, both alloforms protected nearly equally as well against diazoxon exposure with PON1-R192 protecting a bit better and neither protected against paraoxon exposure, in agreement of a lack of increased sensitivity of PON1 null mice to paraoxon exposure. Thus resistance to diazoxon exposure should be governed primarily by an individual’s plasma PON1 levels, whereas resistance to chlorpyrifos oxon exposure depends on plasma PON1 levels as well as position PON1-192 genotype with PON1-R192 providing the best protection.
Li W.-F., L.G. Costa, R.J. Richter, T. Hagen, D.M. Shih, A. Tward, A.J. Lusis and C.E. Furlong. 2000. Catalytic efficiency determines the in vivo efficacy of PON1 for detoxifying organophosphates. Pharmacogenetics 10:767-780.)