Cytochrome P450 and Phase II drug-metabolizing enzymes (CYP and Phase II enzymes)

Cytochrome P450 (CYP) and Phase II enzymes constitute the primary machinery for the biotransformation of drugs and xenobiotics in the human body [1, 5]. Phase I enzymes, dominated by the CYP450 superfamily, typically introduce or expose functional groups through oxidation, reduction, or hydrolysis, often increasing the polarity of the molecule [2, 8]. Phase II enzymes, such as UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), and glutathione S-transferases (GSTs), then conjugate these metabolites with polar endogenous molecules to facilitate their excretion [3, 5]. While essential for detoxification and the synthesis of endogenous compounds like steroids and lipids, these enzymes are also responsible for the bioactivation of pro-carcinogens and the generation of toxic reactive intermediates [4, 10]. In clinical practice, they are major determinants of pharmacokinetic variability, where genetic polymorphisms or drug-induced inhibition/induction can lead to significant drug-drug interactions, therapeutic failure, or severe adverse reactions [8, 9].

Other names

Drug-metabolizing enzymes (DMEs)Phase I and Phase II enzymesXenobiotic-metabolizing enzymesCYP450 system

Drugs interact with these enzymes as substrates, where they undergo chemical modification (oxidation, reduction, hydrolysis, or conjugation); as inhibitors, which decrease enzyme activity and slow the metabolism of co-administered drugs; or as inducers, which increase enzyme expression and accelerate drug clearance [2, 8, 11].