Human cytochrome P450 enzymes (CYP)

Human cytochrome P450 (CYP) enzymes are a superfamily of heme-containing proteins primarily located in the endoplasmic reticulum of hepatocytes, where they play a critical role in the Phase I metabolism of approximately 75-80% of clinical drugs [1][2]. These enzymes catalyze the oxidative, peroxidative, and reductive metabolism of a vast array of endogenous compounds, such as steroids, fatty acids, and vitamins, as well as exogenous xenobiotics and environmental toxins [3]. In the context of pharmacology, CYPs are central to drug clearance, the activation of prodrugs, and the generation of reactive metabolites that can lead to cellular toxicity [4]. Genetic polymorphisms in CYP genes are significant biomarkers for predicting individual drug responses and risks of adverse effects, particularly for enzymes like CYP2D6 and CYP2C19 [5]. Furthermore, because many drugs act as substrates, inhibitors, or inducers of these enzymes, they are the primary mediators of clinically significant drug-drug interactions that can lead to therapeutic failure or toxicity [6]. Understanding the specific CYP isoforms involved in a drug's metabolic pathway is essential for drug development and personalized medicine [4][6]. Sources: [1] Lynch T, Price A. Am Fam Physician. 2007;76(3):391-396. [2] Guengerich FP. Chem Res Toxicol. 2008;21(1):70-83. [3] Nebert DW, Russell DW. Lancet. 2002;360(9340):1155-1162. [4] Zanger UM, Schwab M. Pharmacol Ther. 2013;138(1):103-141. [5] Ingelman-Sundberg M. Pharmacogenomics J. 2005;5(1):6-13. [6] Tornio A, Backman JT. Adv Pharmacol. 2018;83:3-32.

Other names

Cytochrome P450CYP450Heme-thiolate proteinsMicrosomal monooxygenaseP450 superfamily

Drugs interact with CYP enzymes as substrates (undergoing metabolic transformation), inhibitors (decreasing enzymatic activity and increasing co-administered drug levels), or inducers (increasing enzyme expression and decreasing co-administered drug levels) [1][6].