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The Cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes listed—specifically CYP2B6, CYP3A4/5, CYP2C9, CYP2C19, UGT1A1, UGT1A9, and UGT2B7—constitute the core machinery for Phase I and Phase II drug metabolism in the human liver and gastrointestinal tract [1]. CYP enzymes are heme-thiolate proteins that catalyze oxidative, peroxidative, and reductive reactions, while UGT enzymes are glycosyltransferases that catalyze the transfer of glucuronic acid to various functional groups, increasing the water solubility of drugs for renal or biliary excretion [2, 5]. These enzymes are critical in determining the pharmacokinetic profile of over 70% of clinically used drugs [4]. Because their activity is highly susceptible to genetic variation and modulation by other drugs through induction or inhibition, they are the primary focus of regulatory drug-drug interaction (DDI) studies [1, 3]. Variations in these enzymes can lead to profound differences in drug efficacy and safety, making them central to the field of pharmacogenomics and personalized medicine [3].
These enzymes facilitate the biotransformation of drugs through Phase I oxidation (Cytochrome P450s) and Phase II glucuronidation (UDP-glucuronosyltransferases) to convert lipophilic compounds into hydrophilic metabolites for excretion [1, 4, 5].
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