2.1. Effect of hypoxia on CYP expression
CYPs are heme-containing enzymes that metabolize both exogenous and endogenous substances. Exogenous CYPs are members 1–4 of the family and metabolize chemicals, pharmaceuticals, and environmental pollutants. CYP1, CYP2, and CYP3 account for 80% of oxidative metabolism and eliminate approximately 50% of the clinical drugs, and CYP4 is primarily involved in AA metabolism (Zhao et al., 2021). Endogenous CYPs belong comprise CYP 7–51 and are involved in the biosynthesis or catabolism of endogenous compounds, such as steroids, vitamins, and fatty acids. Certain CYPs that metabolize drugs, such as CYP3A4 and CYP3A5, are also involved in the metabolism of endogenous substances.
The activity and expression of CYPs proteins are susceptible to hypoxia. However, there is variability in the results owing to differences in hypoxia modeling methods, study subjects, and hypoxia duration. The results thus far indicate that hypoxia decreases the expression and activity of CYP1A1, CYP1A2, CYP2B6, CYP2C19, CYP2E1, CYP2J2, and CYP3A4, while increasing those of CYP1B1 and CYP2C8. However, the effects of hypoxia on CYP2C9 and CYP2D6, which have high genetic polymorphisms, are not well understood. In addition, the expression of several other CYPs involved in the metabolism of endogenous substances, such as CYP7A1, CYP2S1, CYP24A1, CYP46A1, and CYP2W1, which are either directly involved in the synthesis of endogenous substances, such as fatty acids and vitamins, or are important rate-limiting enzymes in the biosynthesis of endogenous substances, was also affected by hypoxia (Table 1).