Para-oxon hydrolyzing enzymes in rat liver

Abstract

H3-Paraoxon was shown to be degraded by at least four distinct enzymes in rat liver with different p H optima, reaction constants, and sensitivities to metallic ions, SH-reagents, and inhibitors. These enzymes were present in a soluble and a particulate state in the liver cell. The specific activity was highest in the crude microsomes and lower in the washed mitochondria and the crude soluble fraction at the respective optimum pH's. The crude soluble fraction contained two different enzymes which were partially purified by ammonium sulfate fractionation. The washed mitochondrial, crude microsomal, crude and partially purified soluble enzymes produced diethyl phosphate as the principal metabolite. A partially purified soluble fraction produced 0-desethyl paraoxon. The enzymes in microsomes and mitochondria were solubilized by treatment with sodium desoxycholate. The above subcellular fractions also degraded H .-parathion. but not necessarily by the enzymes responsible for paraoxon degradation.oxic organophosphates and fluorophosphates are enzymatically hydrolyzed by various organisms.

Purification and characterization of paraoxon hydrolase from rat liver

“…Our results are similar to those reported for diazoxonase [41] and paraoxonase [42] from rat liver microsomes. However, optimum pH values of 7.7 and 7.4 have been found by others [42,43]. Similar values to those found by us have been reported for paraoxonases from sheep serum [44] and human serum [45].…”

“…The pH optimum determined by us for the purified enzyme (pH 8.5) is identical to that previously reported for rat liver microsomal preparations [40]. Our results are similar to those reported for diazoxonase [41] and paraoxonase [42] from rat liver microsomes. However, optimum pH values of 7.7 and 7.4 have been found by others [42,43].…”

Human liver paraoxonase (PON1): Subcellular distribution and characterization

“…These data suggest some similarity between human plasma and liver paraoxonase. However, the optimum pH found by us for human liver paraoxonase is higher than that reported for other rat liver organophosphorus hydrolases (2,22,23).…”

Purification and characterization of a phosphoric triester hydrolase from the tufted apple bud moth,Platynota idaeusalis (Walker)

“…Since divalent metal cations, specifically manganese and/or cobalt in insects or calcium in mammals, act as cofactors for this group of enzymes, this result is not surprising. Kojima and O'Brien [13] similarly reported that EDTA inhibited PTEH activity from rat liver. This result differs, however, from results seen with the tobacco budworm in which the addition of EDTA had no significant effect on PTEH activity [11].…”

“…In mammals and insects, the major cation cofactors for phosphoric triester hydrolase are calcium and cobalt/manganese, respectively [10][11][12]. Metal chelators like ethylenediaminetetraacetic acid (EDTA) are inhibitory [13]. Although the exact catalytic mechanism is unknown, it is hypothesized that there is a cysteine group at the active site because mercuric compounds like para-chloromercuribenzoate are potent A-esterase inhibitors [14].…”