Species variations in the pathways of drug metabolism.

Rt, Williams

doi:10.1289/ehp.7822133

Cited by 18 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We could confirm the latter by not detecting a feature for these six metabolites generated by human liver S9 but only observing sulfone as well as a dechlorinated metabolite for fipronil. In general, the discrepancy between mammalian metabolites reported in registration dossiers and our experimental findings might reflect the general differences between in vivo and in vitro studies but also the differences in isoform composition, expression, and catalytic activities of enzymes involved in contaminant metabolism between humans and other mammals such as rats …”

Section: Resultscontrasting

confidence: 62%

“…In general, the discrepancy between mammalian metabolites reported in registration dossiers and our experimental findings might reflect the general differences between in vivo and in vitro studies but also the differences in isoform composition, expression, and catalytic activities of enzymes involved in contaminant metabolism between humans and other mammals such as rats. 43…”

Section: ■ Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Improving the Screening Analysis of Pesticide Metabolites in Human Biomonitoring by Combining High-Throughput In Vitro Incubation and Automated LC–HRMS Data Processing

et al. 2021

View full text Add to dashboard Cite

There is a current need to monitor human exposure to a large number of pesticides and other chemicals of emerging concern (CECs). This requires screening analysis with high confidence for these compounds and their metabolites in complex matrices, which is hampered by the fact that no reference standards are available for most metabolites. We address this challenge by a high-throughput workflow based on incubation of pesticides (or other CECs) with human liver S9, followed by solid-phase extraction, liquid chromatography−high-resolution mass spectrometry (LC−HRMS) analysis, and automated data processing to generate a database (retention time, precursor m/z, and MS 2 spectral library) for the annotation in human samples. The metabolite prioritization consists of statistical comparisons and mass defect and m/z range filtering to obtain a subset of probable phase I metabolites, for which molecular formulas and likely metabolic transformation are retrieved. We tested the workflow on 22 pesticides, for which we could determine 91 metabolite molecular formulas which are only partly covered by the literature and/or predicted by in silico metabolization. Our workflow allows for an efficient generation of metabolite reference information, which can be used directly for annotating LC−HRMS data from human samples. A full structure elucidation of individual metabolites can be limited to those being actually present in human samples.

show abstract

Section: Resultscontrasting

confidence: 62%

Section: ■ Results and Discussionmentioning

confidence: 99%

Improving the Screening Analysis of Pesticide Metabolites in Human Biomonitoring by Combining High-Throughput In Vitro Incubation and Automated LC–HRMS Data Processing

et al. 2021

View full text Add to dashboard Cite

show abstract

“…benzoic acid), to name a few, by the respective Nacyltransferases, and this process differs both qualitatively and quantitatively between animals that may be reflective of their evolutionary physiology and dietary habits. 22 In some extreme instances, certain phase II metabolism pathways show a remarkably reduced capacity as seen with glucuronidation in cats and sulfation in pigs. 23 Additionally, aromatization plays a secondary role in adding to the pool of circulating phenolic metabolites, as evident from transformation of dietary alicyclic quinic and shikimic acids into benzoic and hippuric acids prior to excretion.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Methylation occurs both in the cytosol or in the endoplasmic reticulum depending on the presence of soluble or membrane-bound catechol-O-methyltransferase . Alternatively, low molecular weight phenolics can enter mitochondria where they are conjugated with glycine (human, benzoic acid), glutamine (human, phenylacetic acid), ornithine (chicken, benzoic acid), taurine (pigeon, phenylacetic acid), or arginine (spiders, benzoic acid), to name a few, by the respective N-acyltransferases, and this process differs both qualitatively and quantitatively between animals that may be reflective of their evolutionary physiology and dietary habits . In some extreme instances, certain phase II metabolism pathways show a remarkably reduced capacity as seen with glucuronidation in cats and sulfation in pigs .…”

Section: Introductionmentioning

confidence: 99%

All Polyphenols Are Not Created Equal: Exploring the Diversity of Phenolic Metabolites

Vong

Rathinasabapathy

Moncada

et al. 2022

J. Agric. Food Chem.

View full text Add to dashboard Cite

Dietary intake of plant polyphenols is significant, and many of them enter a human body as a highly diverse pool of ring-fission phenolic metabolites arising from digestion and microbial catabolism of the parental structures. Difficulty in designing the uniform intervention studies and limited tools calibrated to detect and quantify the inherent complexity of phenolic metabolites hindered efforts to establish and validate protective health effects of these molecules. Here, we highlight the recent findings that describe novel complex downstream metabolite profiles with a particular focus on dihydrophenolic (phenylpropanoic) acids of microbial origin, ingested and phase II-transformed methylated phenolic metabolites (methylated sinks), and small phenolic metabolites derived from the breakdown of different classes of flavonoids, stilbenoids, and tannins. There is a critical need for precise identification of the individual phenolic metabolite signatures originating from different polyphenol groups to enable future translation of these findings into break-through nutritional interventions and dietary guidelines.

show abstract