Detoxication of paraoxon by rat liver homogenate and serum carboxylesterases and A-esterases*

Tang, Jun; Chambers, Janice E.

doi:10.1002/(sici)1099-0461(1999)13:5<261::aid-jbt6>3.0.co;2-0

Cited by 38 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have seen similar kinetic behavior for other lipophilic pesticides in mice (23), and the Martin's kinetic profiles of DFP show the same delayed peak (13). Peak AChE inhibition occurs 24-48 hr after PTN and chlorpyrifos exposures (24). Anticholinesterases can have differing peak binding times to esterase in vitro (25), casting some doubt on the need for this purely physical delay compartment.…”

Section: Resultssupporting

confidence: 56%

Protein binding of isofluorophate in vivo after coexposure to multiple chemicals.

Vogel

Keating

Buchholz

2002

Environ Health Perspect

View full text Add to dashboard Cite

Full toxicologic profiles of chemical mixtures, including dose-response extrapolations to realistic exposures, is a prohibitive analytical problem, even for a restricted class of chemicals. We present an approach to probing in vivo interactions of pesticide mixtures at relevant low doses using a monitor compound to report the response of biochemical pathways shared by mixture components. We use accelerator mass spectrometry (

show abstract

Section: Resultssupporting

confidence: 56%

Protein binding of isofluorophate in vivo after coexposure to multiple chemicals.

Vogel

Keating

Buchholz

2002

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…Near physiological assay conditions were used to reflect as closely as possible metabolism in vivo and because the hydrolytic activity of the allelic variants of PON1-192 are differentially affected by a number of conditions. For example, it has been reported that nonphysiological conditions of pH and temperature (discussed by O' Leary et al, 2005) and low tissue concentration (Tang and Chambers, 1999) influence oxon hydrolysis measurements that are relevant in vivo. More importantly, high sodium chloride levels markedly and differentially affect the activity of the PON1-192 variants (Li et al, .…”

Section: Discussionmentioning

confidence: 99%

“…More importantly, high sodium chloride levels markedly and differentially affect the activity of the PON1-192 variants (Li et al, . However, to investigate PON1-mediated hydrolysis of the oxons and to limit carboxylesterase-and cholinesterase-mediated covalent binding that is relatively more important at lower concentrations (Tang and Chambers, 1999;Timchalk et al, 2002), this study used nonphysiological, saturating oxon concentrations. O' Leary et al (2005) investigated the relationship between PON1 genotypes and hydrolysis of saturating concentrations of diazoxon using the sera of 47 Caucasian individuals and near-physiological assay conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Microsomes were incubated with saturating concentrations of diazoxon (500 M), chlorpyrifos-oxon (500 M), paraoxon (1 mM), and phenylacetate (3 mM) in 50 mM Tris-HCl/1 mM CaCl 2 buffer, pH 7.4. To investigate PON1-mediated hydrolysis of the oxons, nonphysiological saturating concentrations were used to maximize PON1 hydrolytic activity compared with carboxylesterase-and cholinesterase-mediated covalent binding, which is relatively more important at lower substrate concentrations (Tang and Chambers, 1999;Timchalk et al, 2002). Physiological conditions of pH (pH 7.4), temperature (37°C), and tissue concentration (approximately equivalent to 0.2 g liver/ml) were used to reflect, as closely as possible, enzyme concentrations in intact liver.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The Relationship between PON1 Phenotype and PON1-192 Genotype in Detoxification of Three Oxons by Human Liver

Mutch¹,

Daly²,

Williams³

2006

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Phosphorothioate pesticides (OP) such as diazinon, chlorpyrifos, and parathion are activated to highly toxic oxon metabolites by the cytochromes P450 (P450s), mainly in the liver. Simultaneously, the P450s catalyze detoxification of OP to nontoxic dearylated metabolites. The oxon is then detoxified to the dearylated metabolite by PON1, an A-esterase present in the liver and blood serum. The aims of this study were to define the influence of PON1-192 genotype and phenotype on the capacity of human liver microsomes (n ‫؍‬ 27) to detoxify the oxons diazoxon, chlorpyrifos-oxon, and paraoxon. Near physiological assay conditions were used to reflect as closely as possible metabolism in vivo and because the hydrolytic activity of the allelic variants of PON1-192 are differentially affected by a number of conditions. The rates of hydrolysis of diazoxon, chlorpyrifos-oxon, and paraoxon varied 5.7-, 16-, and 56-fold, respectively, regardless of PON1-192 genotype. Individuals with the PON1-192RR genotype preferentially hydrolyzed paraoxon (p < 0.01), and the R allele was associated with higher hydrolytic activity toward chlorpyrifos-oxon, but not diazoxon. There were strongly significant relationships between phenylacetate and paraoxon hydrolysis (p < 0.001) and phenylacetate and chlorpyrifos-oxon hydrolysis (p < 0.001), but not between phenylacetate and diazoxon hydrolysis. These data highlight the importance of PON1 phenotype for efficient hydrolysis of paraoxon and chlorpyrifos-oxon, but environmental and yet unknown genetic factors are more important than PON1-192 genotype in determining capacity to hydrolyze diazoxon.

show abstract

“…Some of these agents have a selective damaging effect on the male reproductive tract, which eventually manifests itself in disturbances of sperm cell differentiation and maturation (24,25). Carboxylesterases participate in the process of specific OPC detoxification by: (1) binding OPCs to their active centers and, thus, sequestering them in the cell or (2) hydrolyzing the ester bonds of OPC molecules (26,27). These properties of carboxylesterases provided a primarily basis for the development of a concerning the functions of these enzymes in the male reproductive tract.…”

Section: Carboxylesterases: From Canonical Activities and Properties mentioning

confidence: 99%

Carboxylesterases moonlight in the male reproductive tract a functional shift pivotal for male fertility

Михайлов¹

2000

Front Biosci

View full text Add to dashboard Cite

This essay addresses the carboxylesterase redundancy in the male reproductive tract seemingly conserved across phyla. Evidence is provided which suggests that carboxylesterases are recruited by the male reproductive system in certain animal groups. These provide advantageous metabolic capabilities to sperm protection, sperm maturation, and sperm use. Rather than an archival record of the available data, we seek possible answers to the central question: Why is carboxylesterase over-expression adaptive with the functioning of the male reproductive tract with respect to male fertility? We discuss patterns of carboxylesterase over-expression and accumulation in different compartments of the male reproductive tract. We also provide evidence of how these patterns are associated with a long sperm path to egg through different local effects. The hyper-expression of carboxylesterases can play different physiological roles depending on its localization in the male reproductive system. However, all the "acquired" functions can serve the same purpose; creating conditions which maximize the fertilizing potential of the sperm. To confirm our concept and more clearly illuminate "moonlighting" roles of carboxylesterases in the male reproductive tract, requires a more extensive comparative analysis of a variety of carboxylesterases in a larger number of species.

show abstract

Detoxication of paraoxon by rat liver homogenate and serum carboxylesterases and A-esterases*

Cited by 38 publications

References 29 publications

Protein binding of isofluorophate in vivo after coexposure to multiple chemicals.

Protein binding of isofluorophate in vivo after coexposure to multiple chemicals.

The Relationship between PON1 Phenotype and PON1-192 Genotype in Detoxification of Three Oxons by Human Liver

Carboxylesterases moonlight in the male reproductive tract a functional shift pivotal for male fertility

Contact Info

Product

Resources

About