6533b7d2fe1ef96bd125e113
RESEARCH PRODUCT
Toxicological implications of enzymatic control of reactive metabolites.
Pablo SteinbergBarbara Oesch-bartlomowiczThomas FriedbergJohannes DoehmerKarl-ludwig PlattHelmut ThomasDietmar UteschHansruedi GlattFranz Oeschsubject
0301 basic medicineHealth Toxicology and MutagenesisMetaboliteMolecular Sequence DataMutagenBiologyToxicologymedicine.disease_causeGene Expression Regulation Enzymologic03 medical and health scienceschemistry.chemical_compound0302 clinical medicineCytosolEthers CyclicMicrosomesmedicineHumansPsychological repressionCarcinogenGlutathione Transferasechemistry.chemical_classificationEpoxide Hydrolases030102 biochemistry & molecular biologyBase SequenceBiomoleculeGeneral MedicineIsoenzymesEnzymeBiochemistrychemistry030220 oncology & carcinogenesisToxicityEpoxy CompoundsXenobioticdescription
Many foreign compounds are transformed into reactive metabolites, which may produce genotoxic effects by chemically altering critical biomolecules. Reactive metabolites are under the control of activating, inactivating and precursor sequestering enzymes. Such enzymes are under the long-term control of induction and repression, as well as the short-term control of post-translational modification and low molecular weight activators or inhibitors. In addition, the efficiency of these enzyme systems in preventing reactive metabolite-mediated toxicity is directed by their subcellular compartmentalization and isoenzymic multiplicity. Extrapolation from toxicological test systems to the human requires information of these variables in the system in question and in man. Differences in susceptibility to toxic challenges between species and individuals are often causally linked to differences in these control factors.
year | journal | country | edition | language |
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1990-05-01 | Humanexperimental toxicology |