Decoding the Role of CYP450 Enzymes in Metabolism and Disease: A Comprehensive Review

Abstract

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations.

Keywords: CYP450; NAFLD; PCOS; bile acids detoxification; cancer; cirrhosis; fatty acid metabolism; hormone metabolism; lipid metabolism; polymorphism; vitamin D metabolism.

Figure 1

Xenobiotics activate CYP450 gene expression. (1) Xenobiotics translocate to inside the cell. (2) It binds to the NR. (3) Xenobiotic binding induces conformational changes that facilitate its translocation into the nucleus through binding to nuclear translocator. (4) The ligand-bound NR–partner complex nuclear translocator binds to xenobiotic response elements. (5) Initiates the transcription of CYP genes, including those encoding CYP450 enzymes, in various tissues. Created with https://www.biorender.com/ (accessed on 5 June 2024).