Conjugation of xenobiotics with glutathione forms glutathione conjugates. These conjugates can be effluxed into bile and blood and are converted to mercapturic acid in the kidney. In which phase of metabolism does this process belong?

• A. Phase I metabolism or Conjugation phase
• B. Phase II metabolism or Functionalization phase
• C. Phase I metabolism or Functionalization phase
• D. Phase II metabolism or Conjugation phase

Answer: (C)

Glutathione conjugation is a Phase II reaction, the conjugation phase. Phase I reactions (functionalization) primarily introduce or reveal reactive groups on the xenobiotic through oxidation, reduction, or hydrolysis. In this scenario, the xenobiotic is directly attached to glutathione, forming a glutathione conjugate to increase water solubility and prepare it for excretion. This conjugate can be transported into bile or blood, and in the kidney it’s further processed to mercapturic acid, which is then excreted. Since the key step is attaching an endogenous molecule (glutathione) to the xenobiotic to enhance elimination, it fits Phase II metabolism rather than Phase I.