The role of biotransformation and bioactivation in toxicity.
Biotransformation is essential to convert lipophilic chemicals to water-soluble and readily excretable metabolites. Formally, biotransformation reactions are classified into phase I and phase II reactions. Phase I reactions represent the introduction of functional groups, whereas phase II reactions are conjugations of such functional groups with endogenous, polar products. Biotransformation also plays an essential role in the toxicity of many chemicals due to the metabolic formation of toxic metabolites. These may be classified as stable but toxic products, reactive electrophiles, radicals, and reactive oxygen metabolites. The interaction of toxic products formed by biotransformation reactions with cellular macromolecules initiates the sequences resulting in cellular damage, cell death and toxicity.
Dekant
Wolfgang
W
Department of Toxicology, University of Würzburg, Würzburg, Germany. dekant@toxi.uniwuerzburg.de
D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism* / Q000493:pharmacokinetics
D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D011451:Prostaglandin-Endoperoxide Synthases