Carboxylesterases: General detoxifying enzymes

Hatfield, M. Jason; Umans, Robyn A.; Hyatt, Janice L.; Edwards, Carol C.; Wierdl, Monika; Tsurkan, Lyudmila; Taylor, Michael R.; Potter, Philip M.

doi:10.1016/j.cbi.2016.02.011

Cited by 132 publications

(64 citation statements)

References 23 publications

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“…concentrations of SN-38 and SN-38G (Hatfield et al, 2016). This provides evidence of the importance of UDPGA and NADPH as enzyme co-factors in the metabolism of CPT-11.…”

Section: Metabolism Of Cpt-11 In Human Liver Microsomes With Differmentioning

confidence: 63%

“…Some studies have reported little variability in expression of CES1 in human liver microsomes compared with human liver (Hsieh, Lin, Chen, Huang, & Roffler, ). However, CES1 possesses lower catalytic activity for CPT‐11 hydrolysis to SN‐38 than CES2, resulting in lower concentrations of SN‐38 and SN‐38G (Hatfield et al, ). This provides evidence of the importance of UDPGA and NADPH as enzyme co‐factors in the metabolism of CPT‐11.…”

Section: Resultsmentioning

confidence: 99%

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Carboxylesterase and UDP‐glucuronosyltransferases mediated metabolism of irinotecan: In vitro and in vivo insights from quantitative ultra‐performance liquid chromatography–mass spectrometry analysis

Qin

Zhou

et al. 2018

Biomedical Chromatography

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Carboxylesterase and UDP-glucuronosyltransferase-mediated metabolism of irinotecan (CPT-11) has long been proposed to be responsible for its anti-tumor activity and toxicity, like delayed-onset diarrhea. However, recent studies failed to gain more comprehensive in vivo and in vitro pharmacokinetic profiles of irinotecan. Herein, we use rat plasma, human liver microsomes and immortalized HepG2 cell as experimental subjects to describe a sensitive and versatile UHPLC-MS/MS method for simultaneously quantifying CPT-11 and its metabolites, including SN-38 and SN-38G. The method was applied to investigate the pharmacokinetic and metabolic behavior of CPT-11 in the biological samples. Calibration curves for all bio-matrices showed acceptable linearity (r > 0.99). The intra- and inter-day precisions (RSD, %) were within 15% and the excellent accuracy (RE) was between 2.96 and 14.12%. In addition, the specificity, matrix effect and extraction recovery all met the requirements of biological sample analysis. We successfully applied this method to investigate the pharmacokinetics of irinotecan in various biological samples, mediated by carboxylesterase and UDP-glucuronosyltransferase. This method could be employed in monitoring the metabolic status and clinical efficacy of irinotecan in the future.

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“…concentrations of SN-38 and SN-38G (Hatfield et al, 2016). This provides evidence of the importance of UDPGA and NADPH as enzyme co-factors in the metabolism of CPT-11.…”

Section: Metabolism Of Cpt-11 In Human Liver Microsomes With Differmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Carboxylesterase and UDP‐glucuronosyltransferases mediated metabolism of irinotecan: In vitro and in vivo insights from quantitative ultra‐performance liquid chromatography–mass spectrometry analysis

Qin

Zhou

et al. 2018

Biomedical Chromatography

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“…Organophosphates are detoxified by the action of carboxylesterase 15 . Carboxylesterases (β-esterase or non-specific esterases) are group of hydrolytic enzymes important in the metabolism and subsequent detoxification of many xenobiotic and endogenous compounds, including Ops 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Untitled

2018

IJPSR

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Organophosphate pesticides are associated with neurotoxicity. Organophosphates are cholinesterase-inhibiting chemicals used predominately as pesticides. These have played a very important role in sustainable production of food, animal feed and as protection against disease vectors. They are also used as chemical warfare agents (nerve agents). The effects of dichlorvos and monocrotophos on brain neurotransmitters are well established. The combined effect of organophosphates (dichlorvos and monocrotophos) was supposed to have synergistic or additive effect on brain neurotransmitters. Combined exposure of dichlorvos and monocrotophos has significant inhibition in acetylcholine esterase activity during both studies of 15 days and 30 days. Levels of nor-epinephrine, dopamine and serotonin (5-hydroxytryptamine) increased significantly in dichlorvos and monocrotophos exposed animals. However, the increase was more pronounced in monocrotophos alone exposed animals. Thus, contrary to hypothesis, the combined exposure to these toxicants did not produce more pronounced toxicity as compared to their individual exposure except in case of nor-epinephrine.

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“…Research on mammalian carboxylesterases has primarily focused on their role in xenobiotic metabolism [4]. They metabolize and increase the clearance of drugs such as methylphenidate [5] and pesticides including pyrethroids [6].…”

Section: Introductionmentioning

confidence: 99%

Development of amide-based fluorescent probes for selective measurement of carboxylesterase 1 activity in tissue extracts

Kodani

Barthélemy

Kamita

et al. 2017

Analytical Biochemistry

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Carboxylesterases are well known for their role in the metabolism of xenobiotics. However, recent studies have also implicated carboxylesterases in regulating a number of physiological processes including metabolic homeostasis and macrophage development, underlying the need to quantify them individually. Unfortunately, current methods for selectively measuring the catalytic activity of individual carboxylesterases are not sufficiently sensitive to support many biological studies. In order to develop a more sensitive and selective method to measure the activity of human carboxylesterase 1 (hCE1), we generated and tested novel substrates with a fluorescent aminopyridine leaving group. hCE1 showed at least a 10-fold higher preference for the optimized substrate 4-MOMMP than the 13 other esterases tested. Because of the high stability of 4-MOMMP and its hydrolysis product, this substrate can be used to measure esterase activity over extended incubation periods yielding a low picogram (femtomol) limit of detection. This sensitivity is comparable to current ELISA methods; however, the new assay quantifies only the catalytically active enzyme facilitating direct correlation to biological processes. The method described herein may allow hCE1 activity to be used as a biomarker for predicting drug pharmacokinetics, early detection of hepatocellular carcinoma, and other disease states where the activity of hCE1 is altered.

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Carboxylesterases: General detoxifying enzymes

Cited by 132 publications

References 23 publications

Carboxylesterase and UDP‐glucuronosyltransferases mediated metabolism of irinotecan: In vitro and in vivo insights from quantitative ultra‐performance liquid chromatography–mass spectrometry analysis

Carboxylesterase and UDP‐glucuronosyltransferases mediated metabolism of irinotecan: In vitro and in vivo insights from quantitative ultra‐performance liquid chromatography–mass spectrometry analysis

Untitled

Development of amide-based fluorescent probes for selective measurement of carboxylesterase 1 activity in tissue extracts

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