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The page below is a sample from the LabCE course Drug Metabolism. Access the complete course and earn ASCLS P.A.C.E.-approved continuing education credits by subscribing online.

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Phase II Metabolic Reactions

The metabolites of phase I metabolic reactions can either be directly excreted in the urine or undergo further metabolic reactions. An important point to note is that some drugs don’t undergo phase I metabolic reaction but instead are directly deactivated by phase II reactions. The enzymes of phase I metabolism, most notably the cytochrome P450 enzymes, only slightly increase the water solubility of the drug molecule and do not always increase it enough to facilitate elimination. However, they do destabilize and unmask or expose a functional group. The exposed functional group allows for the attachment of water soluble sugars, salts, or amino acids that make the molecule heavier and more water soluble.
Phase II metabolic reactions are characterized as conjugation reactions and are catalyzed by enzymes known as transferases. Transferases link or conjugate polar functional groups of phase I metabolites with molecules containing the following hydrophilic functional groups:
  • Glucuronic acid (glucose metabolite) conjugation by UDP glucuronyl transferase
  • Sulfate conjugation by sulfotransferases
  • Glutathione conjugation with reactive metabolic products by glutathione S- transferases
  • Amino acid conjugation by acyl-CoA synthetase and N-acetyltransferase
  • Acetylation- attachment of an acetyl group by N-acetyl transferases
  • Methylation- attachment of a methyl group by methyl transferases