Your browser does not fully support modern features. Please upgrade for a smoother experience.
Drug Biotransformation: History
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor: Yu Peng

Drug biotransformation designates the enzymatic conversion of a drug molecule into one or more metabolites within the body, a process that generally increases the polarity and water solubility of the compound and thereby facilitates its elimination in urine or bile [1]. The process is conventionally organized into two sequential but functionally coupled phases: phase I reactions introduce or unmask a reactive or polar functional group through oxidation, reduction, or hydrolysis, while phase II reactions conjugate the drug or its phase I metabolite with an endogenous moiety—glucuronic acid, sulfate, glutathione, or an acetyl group—yielding a product of markedly greater polarity and molecular weight [2][3]. The phase I oxidative reactions are catalyzed predominantly by the cytochrome P450 (CYP) superfamily, membrane-bound hemoproteins that account for the majority of oxidative drug metabolism; the principal phase II conjugating enzymes include UDP-glucuronosyltransferases (UGTs), sulfotransferases, glutathione S-transferases, and N-acetyltransferases [1][3]. A defining feature of drug biotransformation is that the metabolic outcome is not uniformly detoxifying: the same enzymatic transformation can convert a pharmacologically inert prodrug into its active form or generate a reactive, toxic metabolite from a stable parent compound, a phenomenon termed bioactivation [4]. Within pharmacogenetics and drug metabolism, the term encompasses the enzyme systems, reaction types, and metabolic pathways that collectively determine a drug’s pharmacokinetic profile, its duration of action, and its potential for toxicity, together with the genetic and environmental factors that produce interindividual variability in these pathways [1][5].

  • Phase I metabolism
  • phase II conjugation
  • cytochrome P450
  • UDP-glucuronosyltransferase

Pharmacogenetics and Drug Metabolism·Pharmacology·Pharmacology, Toxicology and Pharmaceutics·Life Sciences

References

  1. Mingzhe Zhao; Jingsong Ma; Mo Li; Yingtian Zhang; Bixuan Jiang; Xianglong Zhao; Cong Huai; Lu Shen; Na Zhang; Lin He; et al. Cytochrome P450 Enzymes and Drug Metabolism in Humans. Int. J. Mol. Sci. 2021, 22, 12808, 10.3390/ijms222312808.
  2. Na Yang; Runbin Sun; Xiaoying Liao; Jiye Aa; Guangji Wang; UDP-glucuronosyltransferases (UGTs) and their related metabolic cross-talk with internal homeostasis: A systematic review of UGT isoforms for precision medicine. Pharmacol. Res. 2017, 121, 169-183, 10.1016/j.phrs.2017.05.001.
  3. Petra Jancova; Pavel Anzenbacher; Eva Anzenbacherova; PHASE II DRUG METABOLIZING ENZYMES. Biomed. Pap. 2010, 154, 103-116, 10.5507/bp.2010.017.
  4. John S. Walsh; Gerald T. Miwa; Bioactivation of Drugs: Risk and Drug Design. Annu. Rev. Pharmacol. Toxicol. 2011, 51, 145-167, 10.1146/annurev-pharmtox-010510-100514.
  5. Shabbir Ahmed; Zhan Zhou; Jie Zhou; Shu-Qing Chen; Pharmacogenomics of Drug Metabolizing Enzymes and Transporters: Relevance to Precision Medicine. Genom. Proteom. Bioinform. 2016, 14, 298-313, 10.1016/j.gpb.2016.03.008.
More
This entry is offline, you can click here to edit this entry!
Write an Entry