Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes
Raunio, H., Kuusisto, M., Juvonen, R. O., & Pentikäinen, O. (2015). Modeling of interactions between xenobiotics and cytochrome P450 (CYP) enzymes. Frontiers in Pharmacology, 6, Article 123. https://doi.org/10.3389/fphar.2015.00123
Published inFrontiers in Pharmacology
Copyright © 2015 Raunio, Kuusisto, Juvonen and Pentikäinen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
The adverse effects to humans and environment of only few chemicals are well known. Absorption, distribution, metabolism, and excretion (ADME) are the steps of pharmaco/toxicokinetics that determine the internal dose of chemicals to which the organism is exposed. Of all the xenobiotic-metabolizing enzymes, the cytochrome P450 (CYP) enzymes are the most important due to their abundance and versatility. Reactions catalyzed by CYPs usually turn xenobiotics to harmless and excretable metabolites, but sometimes an innocuous xenobiotic is transformed into a toxic metabolite. Data on ADME and toxicity properties of compounds are increasingly generated using in vitro and modeling (in silico) tools. Both physics-based and empirical modeling approaches are used. Numerous ligand-based and target-based as well as combined modeling methods have been employed to evaluate determinants of CYP ligand binding as well as predicting sites of metabolism and inhibition characteristics of test molecules. In silico prediction of CYP–ligand interactions have made crucial contributions in understanding (1) determinants of CYP ligand binding recognition and affinity; (2) prediction of likely metabolites from substrates; (3) prediction of inhibitors and their inhibition potency. Truly predictive models of toxic outcomes cannot be created without incorporating metabolic characteristics; in silico methods help producing such information and filling gaps in experimentally derived data. Currently modeling methods are not mature enough to replace standard in vitro and in vivo approaches, but they are already used as an important component in risk assessment of drugs and other chemicals. ...
PublisherFrontiers Research Foundation
Publication in research information system
MetadataShow full item record
Except where otherwise noted, this item's license is described as Copyright © 2015 Raunio, Kuusisto, Juvonen and Pentikäinen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Showing items with similar title or keywords.
Intrinsic aerobic capacity governs the associations between gut microbiota composition and fat metabolism age-dependently in rat siblings Pekkala, Satu; Lensu, Sanna; Nokia, Miriam; Vanhatalo, Sanja; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki (American Physiological Society, 2017)Host genetic factors affecting the gut microbiome play an important role in obesity, yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study ...
Energy cost of individual lower leg muscles in walking : comparison between young and elderly men at different walking speeds Pincheira, Patricio (2015)The cost of transport (COT) in elderly subjects is increased in comparison to young adults, independently of the walking speed. The changes in the neuromuscular activity of the lower extremity muscles could explain this ...
“Do you understand (me)?” negotiating mutual understanding by using gaze and environmentally coupled gestures between two deaf signing participants Sivunen, Nina; Tapio, Elina (De Gruyter Mouton, 2020)In this paper we explore the use of multimodal and multilingual semiotic resources in interactions between two deaf signing participants, a researcher and an asylum seeker. The focus is on the use of gaze and environmentally ...
Relations between teacher-child interactions and children's learning and motivation in Finnish kindergartens Pakarinen, Eija (University of Jyväskylä, 2012)
Humour in EFL classrooms : a comparative case study between elementary and secondary school lessons Paajoki, Sanna (2014)Tämä laadullinen tapaustutkimus pyrkii selvittämään sekä opettaja- että oppilasaloitteisen huumorin roolia opetuksessa. Ilmiötä tarkastellaan eri huumorilajien kautta: ironia, kiusoittelu, leikinlasku, kielellä leikittely ...