Structured Review

ADMET Predictor pcbs
I n silico predictions and in vitro incubations show that chiral <t>PCBs</t> are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. <t>ADMET</t> Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
Pcbs, supplied by ADMET Predictor, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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93/100 stars

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1) Product Images from "HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES"

Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

Journal: Environmental science & technology

doi: 10.1021/acs.est.8b05250

I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
Figure Legend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

Techniques Used: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
Figure Legend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

Techniques Used: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

2) Product Images from "HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES"

Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

Journal: Environmental science & technology

doi: 10.1021/acs.est.8b05250

I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
Figure Legend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

Techniques Used: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

3) Product Images from "HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES"

Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

Journal: Environmental science & technology

doi: 10.1021/acs.est.8b05250

I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
Figure Legend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

Techniques Used: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
Figure Legend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

Techniques Used: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

4) Product Images from "HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES"

Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

Journal: Environmental science & technology

doi: 10.1021/acs.est.8b05250

I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
Figure Legend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

Techniques Used: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

Chiral PCB 91, PCB 95, PCB 132 and PCB 136 are oxidized in a congener-specific manner by human CYP2A6 and CYP2B6 to OH-PCBs. Representative GC-TOF chromatograms of OH-PCB metabolites (as methylated derivatives) in extracts from incubations of CYP2A6 with (A1) PCB 91; (A2) PCB 95; (A3) PCB 132; and (A4) PCB 136; and in extracts from incubations of CYP2B6 with (B1) PCB 91 and (B2) PCB 132. Incubation conditions were as follow: 50 μM PCB; 60 minutes, 37 ºC; and 10 pmol/mL P450. See the Supporting Information for the corresponding mass spectra. The metabolites were separated on DB5-ms column; see the Experimental Section above for additional details. a No mass spectra were obtained due to low analyte levels. However, the peak was identified by matching the retention time with the authentic standard. b Accurate mass not determined due to background carbon interference. RS, peak corresponding to the recovery standard.
Figure Legend Snippet: Chiral PCB 91, PCB 95, PCB 132 and PCB 136 are oxidized in a congener-specific manner by human CYP2A6 and CYP2B6 to OH-PCBs. Representative GC-TOF chromatograms of OH-PCB metabolites (as methylated derivatives) in extracts from incubations of CYP2A6 with (A1) PCB 91; (A2) PCB 95; (A3) PCB 132; and (A4) PCB 136; and in extracts from incubations of CYP2B6 with (B1) PCB 91 and (B2) PCB 132. Incubation conditions were as follow: 50 μM PCB; 60 minutes, 37 ºC; and 10 pmol/mL P450. See the Supporting Information for the corresponding mass spectra. The metabolites were separated on DB5-ms column; see the Experimental Section above for additional details. a No mass spectra were obtained due to low analyte levels. However, the peak was identified by matching the retention time with the authentic standard. b Accurate mass not determined due to background carbon interference. RS, peak corresponding to the recovery standard.

Techniques Used: Methylation, Incubation

Formation rates of PCB metabolites (analyzed as methylated derivatives) reveal that (A) PCB 91; (B), PCB 95, (C) PCB 132 and (D) PCB 136 are metabolized to OH-PCBs by human CYP2A6, CYP2B6, and CYP2E1. c Incubation with CYP2E1 for 60 min. d Data are presented as mean ± standard deviation, n = 3.
Figure Legend Snippet: Formation rates of PCB metabolites (analyzed as methylated derivatives) reveal that (A) PCB 91; (B), PCB 95, (C) PCB 132 and (D) PCB 136 are metabolized to OH-PCBs by human CYP2A6, CYP2B6, and CYP2E1. c Incubation with CYP2E1 for 60 min. d Data are presented as mean ± standard deviation, n = 3.

Techniques Used: Methylation, Incubation, Standard Deviation

Related Articles

Incubation:

Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES
Article Snippet: .. To confirm which human P450 isoforms are involved in the metabolism of chiral PCBs to OH-PCBs, racemic PCB 91, PCB 95, PCB 132 and PCB 136 were incubated with the recombinant human P450 isoforms identified with ADMET Predictor and MetaDrug. ..

Recombinant:

Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES
Article Snippet: .. To confirm which human P450 isoforms are involved in the metabolism of chiral PCBs to OH-PCBs, racemic PCB 91, PCB 95, PCB 132 and PCB 136 were incubated with the recombinant human P450 isoforms identified with ADMET Predictor and MetaDrug. ..

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  • 93
    ADMET Predictor pcbs
    I n silico predictions and in vitro incubations show that chiral <t>PCBs</t> are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. <t>ADMET</t> Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
    Pcbs, supplied by ADMET Predictor, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/pcbs/product/ADMET Predictor
    Average 93 stars, based on 1 article reviews
    Price from $9.99 to $1999.99
    pcbs - by Bioz Stars, 2020-09
    93/100 stars
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    93
    ADMET Predictor pcb 132
    OH-PCB metabolites are formed atropselectively from (A) PCB 91, (B) PCB 95, (C) <t>PCB</t> 132 and (D) PCB 136 in incubations with recombinant human CYP2A6 (dark red), CYP2B6 (orange) and CYP2E1 (light green) enzymes. No metabolites were detected in experiments with CYP1A2 and CYP3A4. Open circles (○), diamonds (◇) and squares (□) indicate 1,2-shift, meta- and para -substituted metabolites, respectively. Data are expressed as mean ± SD, n = 3; error bars are typically hidden behind the symbols. Metabolism studies were performed using the following incubation conditions: 50 μM PCB; 60 min incubation at 37 ºC; 10 pmol/mL P450 content; and ~1 mM NADPH regenerating system. Metabolites were separated on BDM (5–91, 4–91, 3–103 and 4’−95); GTA (3–100, 3’−140) or CD columns (5’−132, 3–150, 5– 136 and 4–136). EF value of 5–95 and 4–95 could not be calculated due to co-elution of E 1 -5–95 and E 1 -4–95.
    Pcb 132, supplied by ADMET Predictor, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/result/pcb 132/product/ADMET Predictor
    Average 93 stars, based on 1 article reviews
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    93
    ADMET Predictor oh pcbs
    I n silico predictions and in vitro incubations show that chiral <t>PCBs</t> are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human <t>P450</t> isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).
    Oh Pcbs, supplied by ADMET Predictor, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

    Article Snippet: In addition, MetaDrug predicted the oxidation of chiral PCBs to arene oxide, dihydrodiol, and other metabolites, thus suggesting more complex metabolic pathways for PCBs than predicted by ADMET Predictor.

    Techniques: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

    OH-PCB metabolites are formed atropselectively from (A) PCB 91, (B) PCB 95, (C) PCB 132 and (D) PCB 136 in incubations with recombinant human CYP2A6 (dark red), CYP2B6 (orange) and CYP2E1 (light green) enzymes. No metabolites were detected in experiments with CYP1A2 and CYP3A4. Open circles (○), diamonds (◇) and squares (□) indicate 1,2-shift, meta- and para -substituted metabolites, respectively. Data are expressed as mean ± SD, n = 3; error bars are typically hidden behind the symbols. Metabolism studies were performed using the following incubation conditions: 50 μM PCB; 60 min incubation at 37 ºC; 10 pmol/mL P450 content; and ~1 mM NADPH regenerating system. Metabolites were separated on BDM (5–91, 4–91, 3–103 and 4’−95); GTA (3–100, 3’−140) or CD columns (5’−132, 3–150, 5– 136 and 4–136). EF value of 5–95 and 4–95 could not be calculated due to co-elution of E 1 -5–95 and E 1 -4–95.

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: OH-PCB metabolites are formed atropselectively from (A) PCB 91, (B) PCB 95, (C) PCB 132 and (D) PCB 136 in incubations with recombinant human CYP2A6 (dark red), CYP2B6 (orange) and CYP2E1 (light green) enzymes. No metabolites were detected in experiments with CYP1A2 and CYP3A4. Open circles (○), diamonds (◇) and squares (□) indicate 1,2-shift, meta- and para -substituted metabolites, respectively. Data are expressed as mean ± SD, n = 3; error bars are typically hidden behind the symbols. Metabolism studies were performed using the following incubation conditions: 50 μM PCB; 60 min incubation at 37 ºC; 10 pmol/mL P450 content; and ~1 mM NADPH regenerating system. Metabolites were separated on BDM (5–91, 4–91, 3–103 and 4’−95); GTA (3–100, 3’−140) or CD columns (5’−132, 3–150, 5– 136 and 4–136). EF value of 5–95 and 4–95 could not be calculated due to co-elution of E 1 -5–95 and E 1 -4–95.

    Article Snippet: Predictions of P450 isoforms potentially involved in PCB 91, PCB 95, PCB 132 and PCB 136 oxidative metabolism, as well as possible sites of metabolism, were carried out using ADMET Predictor software (Simulations Plus, Lancaster, CA, USA).

    Techniques: Recombinant, Incubation, Co-Elution Assay

    Simplified metabolism scheme showing the chemical structures and abbreviations of metabolites of PCB 91, PCB 95, PCB 132 and PCB 136 identified in incubations with human P450 enzymes. For the chemical names of the different PCB metabolites, see the Supporting Information.

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: Simplified metabolism scheme showing the chemical structures and abbreviations of metabolites of PCB 91, PCB 95, PCB 132 and PCB 136 identified in incubations with human P450 enzymes. For the chemical names of the different PCB metabolites, see the Supporting Information.

    Article Snippet: Predictions of P450 isoforms potentially involved in PCB 91, PCB 95, PCB 132 and PCB 136 oxidative metabolism, as well as possible sites of metabolism, were carried out using ADMET Predictor software (Simulations Plus, Lancaster, CA, USA).

    Techniques:

    Chiral PCB 91, PCB 95, PCB 132 and PCB 136 are oxidized in a congener-specific manner by human CYP2A6 and CYP2B6 to OH-PCBs. Representative GC-TOF chromatograms of OH-PCB metabolites (as methylated derivatives) in extracts from incubations of CYP2A6 with (A1) PCB 91; (A2) PCB 95; (A3) PCB 132; and (A4) PCB 136; and in extracts from incubations of CYP2B6 with (B1) PCB 91 and (B2) PCB 132. Incubation conditions were as follow: 50 μM PCB; 60 minutes, 37 ºC; and 10 pmol/mL P450. See the Supporting Information for the corresponding mass spectra. The metabolites were separated on DB5-ms column; see the Experimental Section above for additional details. a No mass spectra were obtained due to low analyte levels. However, the peak was identified by matching the retention time with the authentic standard. b Accurate mass not determined due to background carbon interference. RS, peak corresponding to the recovery standard.

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: Chiral PCB 91, PCB 95, PCB 132 and PCB 136 are oxidized in a congener-specific manner by human CYP2A6 and CYP2B6 to OH-PCBs. Representative GC-TOF chromatograms of OH-PCB metabolites (as methylated derivatives) in extracts from incubations of CYP2A6 with (A1) PCB 91; (A2) PCB 95; (A3) PCB 132; and (A4) PCB 136; and in extracts from incubations of CYP2B6 with (B1) PCB 91 and (B2) PCB 132. Incubation conditions were as follow: 50 μM PCB; 60 minutes, 37 ºC; and 10 pmol/mL P450. See the Supporting Information for the corresponding mass spectra. The metabolites were separated on DB5-ms column; see the Experimental Section above for additional details. a No mass spectra were obtained due to low analyte levels. However, the peak was identified by matching the retention time with the authentic standard. b Accurate mass not determined due to background carbon interference. RS, peak corresponding to the recovery standard.

    Article Snippet: Predictions of P450 isoforms potentially involved in PCB 91, PCB 95, PCB 132 and PCB 136 oxidative metabolism, as well as possible sites of metabolism, were carried out using ADMET Predictor software (Simulations Plus, Lancaster, CA, USA).

    Techniques: Methylation, Incubation

    Formation rates of PCB metabolites (analyzed as methylated derivatives) reveal that (A) PCB 91; (B), PCB 95, (C) PCB 132 and (D) PCB 136 are metabolized to OH-PCBs by human CYP2A6, CYP2B6, and CYP2E1. c Incubation with CYP2E1 for 60 min. d Data are presented as mean ± standard deviation, n = 3.

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: Formation rates of PCB metabolites (analyzed as methylated derivatives) reveal that (A) PCB 91; (B), PCB 95, (C) PCB 132 and (D) PCB 136 are metabolized to OH-PCBs by human CYP2A6, CYP2B6, and CYP2E1. c Incubation with CYP2E1 for 60 min. d Data are presented as mean ± standard deviation, n = 3.

    Article Snippet: Predictions of P450 isoforms potentially involved in PCB 91, PCB 95, PCB 132 and PCB 136 oxidative metabolism, as well as possible sites of metabolism, were carried out using ADMET Predictor software (Simulations Plus, Lancaster, CA, USA).

    Techniques: Methylation, Incubation, Standard Deviation

    I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: I n silico predictions and in vitro incubations show that chiral PCBs are metabolized to hydroxylated metabolites by human CYP2A6, CYP2B6, and CYP2E1. ADMET Predictor and Metadrug software packages were initially used to predict human P450 isoforms involved in the metabolism of chiral PCBs. Metabolism studies with recombinant human P450 enzymes were performed to assess if the P450 isoforms identified in silico indeed form OH-PCBs. In vitro Data are presented as mean ± standard deviation, n = 3. a ✓ indicates that the OH-PCB metabolite was predicted to be formed. b In vitro metabolite formation rate (+) below 80 fmol/pmol P450/min, (++) between 80 and 180 fmol/pmol P450/min, (+++) between 180 and 420 fmol/pmol P450/min and (++++) above 420 fmol/pmol P450/min. c Experimental data for incubation with CYP2E1 for 60 min are shown. d Peak corresponding to this metabolite was below the limit of detection (LOD).

    Article Snippet: To confirm which human P450 isoforms are involved in the metabolism of chiral PCBs to OH-PCBs, racemic PCB 91, PCB 95, PCB 132 and PCB 136 were incubated with the recombinant human P450 isoforms identified with ADMET Predictor and MetaDrug.

    Techniques: In Vitro, Software, Recombinant, In Silico, Standard Deviation, Incubation

    Chiral PCB 91, PCB 95, PCB 132 and PCB 136 are oxidized in a congener-specific manner by human CYP2A6 and CYP2B6 to OH-PCBs. Representative GC-TOF chromatograms of OH-PCB metabolites (as methylated derivatives) in extracts from incubations of CYP2A6 with (A1) PCB 91; (A2) PCB 95; (A3) PCB 132; and (A4) PCB 136; and in extracts from incubations of CYP2B6 with (B1) PCB 91 and (B2) PCB 132. Incubation conditions were as follow: 50 μM PCB; 60 minutes, 37 ºC; and 10 pmol/mL P450. See the Supporting Information for the corresponding mass spectra. The metabolites were separated on DB5-ms column; see the Experimental Section above for additional details. a No mass spectra were obtained due to low analyte levels. However, the peak was identified by matching the retention time with the authentic standard. b Accurate mass not determined due to background carbon interference. RS, peak corresponding to the recovery standard.

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: Chiral PCB 91, PCB 95, PCB 132 and PCB 136 are oxidized in a congener-specific manner by human CYP2A6 and CYP2B6 to OH-PCBs. Representative GC-TOF chromatograms of OH-PCB metabolites (as methylated derivatives) in extracts from incubations of CYP2A6 with (A1) PCB 91; (A2) PCB 95; (A3) PCB 132; and (A4) PCB 136; and in extracts from incubations of CYP2B6 with (B1) PCB 91 and (B2) PCB 132. Incubation conditions were as follow: 50 μM PCB; 60 minutes, 37 ºC; and 10 pmol/mL P450. See the Supporting Information for the corresponding mass spectra. The metabolites were separated on DB5-ms column; see the Experimental Section above for additional details. a No mass spectra were obtained due to low analyte levels. However, the peak was identified by matching the retention time with the authentic standard. b Accurate mass not determined due to background carbon interference. RS, peak corresponding to the recovery standard.

    Article Snippet: To confirm which human P450 isoforms are involved in the metabolism of chiral PCBs to OH-PCBs, racemic PCB 91, PCB 95, PCB 132 and PCB 136 were incubated with the recombinant human P450 isoforms identified with ADMET Predictor and MetaDrug.

    Techniques: Methylation, Incubation

    Formation rates of PCB metabolites (analyzed as methylated derivatives) reveal that (A) PCB 91; (B), PCB 95, (C) PCB 132 and (D) PCB 136 are metabolized to OH-PCBs by human CYP2A6, CYP2B6, and CYP2E1. c Incubation with CYP2E1 for 60 min. d Data are presented as mean ± standard deviation, n = 3.

    Journal: Environmental science & technology

    Article Title: HUMAN CYP2A6, CYP2B6 AND CYP2E1 ATROPSELECTIVELY METABOLIZE POLYCHLORINATED BIPHENYLS TO HYDROXYLATED METABOLITES

    doi: 10.1021/acs.est.8b05250

    Figure Lengend Snippet: Formation rates of PCB metabolites (analyzed as methylated derivatives) reveal that (A) PCB 91; (B), PCB 95, (C) PCB 132 and (D) PCB 136 are metabolized to OH-PCBs by human CYP2A6, CYP2B6, and CYP2E1. c Incubation with CYP2E1 for 60 min. d Data are presented as mean ± standard deviation, n = 3.

    Article Snippet: To confirm which human P450 isoforms are involved in the metabolism of chiral PCBs to OH-PCBs, racemic PCB 91, PCB 95, PCB 132 and PCB 136 were incubated with the recombinant human P450 isoforms identified with ADMET Predictor and MetaDrug.

    Techniques: Methylation, Incubation, Standard Deviation