Which hepatic metabolism phase is responsible for functionalization of drugs?

• A. Phase II
• B. Phase I
• C. Phase III
• D. Phase IV

Answer: (B)

Functionalization is the process of introducing or exposing a polar group on a drug molecule to make it more water-soluble. In hepatic metabolism, this work is done mainly by Phase I reactions, such as oxidation, reduction, and hydrolysis. These transformations are often led by enzymes like the cytochrome P450 family and serve to add or reveal functional groups (for example, hydroxyl groups), which sets the stage for the next step. After Phase I has introduced these functional handles, Phase II kicks in to conjugate the molecule with endogenous molecules (like glucuronic acid or sulfate) to greatly increase water solubility and facilitate elimination. Phase III then involves transporters that move the conjugated metabolites out of liver cells toward bile or urine, and Phase IV is not the primary metabolic processing phase. So the phase responsible for functionalization is Phase I.