P450mediated

P450-mediated refers to biochemical transformations carried out by the cytochrome P450 enzyme family, a large and diverse group of heme-thiolate monooxygenases that metabolize a wide range of endogenous and exogenous compounds. In humans, these enzymes catalyze oxidation reactions that typically introduce or unmask a polar group, increasing solubility for excretion (phase I metabolism).

Most P450-catalyzed reactions proceed via a catalytic cycle in which substrate binds to the ferrous heme iron, electrons are donated from NADPH through P450 reductase, oxygen is activated, and one atom of molecular oxygen is incorporated into the substrate while the other forms water. The prevailing outcome is hydroxylation, but the enzymes also perform epoxidation, N-, S-, and O-oxidation, desaturation, dealkylation, and ring opening.

Major human enzymes include CYP3A4/5, CYP2D6, CYP2C9, CYP2C19, CYP1A2, among others. The liver and intestinal wall are rich sources; activity is subject to genetic polymorphisms, induction, and inhibition by drugs and foods.

Consequences of P450-mediated metabolism include variable drug clearance, drug-drug interactions, and the potential formation of toxic or reactive metabolites. Understanding P450-mediated metabolism informs dosing, risk assessment, and prodrug design, and it underpins consideration of drug interactions and adverse effects in clinical pharmacology.