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 a 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 help to destabilize and unmask or expose functional groups. The exposed functional group then allows for phase II reactions. In phase II, the attachment of water-soluble sugars, salts, or amino acids makes the molecule even 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
