A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar, it must undergo an additional phase II reaction. This subsequent reaction converts the nonpolar metabolite into a polar conjugate, enhancing its excretability. During hepatic drug oxidation, the oxidized form of P450 initially binds with the parent drug, creating a binary-drug complex. This complex is then reduced by NADPH–P450 reductase. Following this reduction, the complex uses molecular oxygen and another electron to form an "activated oxygen"-P450-substrate complex. The activated oxygen is then transferred to the drug, creating the oxidized drug metabolite. In conclusion, the monooxygenase P450 cycle plays a crucial role in a phase I reaction, oxidizing a parent drug and introducing a hydroxyl group.
