Cytochrome P450 family 1 subfamily A member 2 (CYP1A2) (CYP1A2)

Cytochrome P450 family 1 subfamily A member 2 (CYP1A2) is a critical hepatic enzyme belonging to the cytochrome P450 superfamily, representing approximately 13% of the total P450 content in the human liver (UniProt: P05177). It is primarily responsible for the oxidative metabolism of a wide range of xenobiotics and endogenous compounds, including caffeine, theophylline, and several antipsychotic and antidepressant medications (PubMed: 25107060). Beyond its role in drug clearance, CYP1A2 is involved in the bioactivation of various pro-carcinogens, such as heterocyclic amines and polycyclic aromatic hydrocarbons found in cooked meat and tobacco smoke, which can lead to DNA adduct formation and increased cancer risk (NIH: Gene ID 1544). The enzyme's activity is highly inducible by environmental factors, most notably polycyclic aromatic hydrocarbons in cigarette smoke, which can significantly lower the plasma concentration of its substrates (StatPearls: Cytochrome P450). Conversely, drugs like fluvoxamine are potent inhibitors of CYP1A2; their co-administration with CYP1A2 substrates can lead to clinically significant increases in drug exposure and potential toxicity (DrugBank: DB00175). Consequently, CYP1A2 is a major focus in clinical pharmacology for predicting drug-drug interactions and tailoring personalized therapeutic regimens.

Other names

Cytochrome P450 1A2CP12P450(PA)CYPIA2P450-P3Cholesterol 24-hydroxylase (incorrectly associated in some older texts, primarily CYP46A1)Aryl hydrocarbon hydroxylase

CYP1A2 catalyzes the oxidative metabolism (typically hydroxylation or dealkylation) of substrates by utilizing molecular oxygen and electrons from NADPH-cytochrome P450 reductase. Drugs like fluvoxamine act as potent competitive inhibitors, binding to the enzyme's active site and preventing the metabolism of other substrates, which leads to increased plasma concentrations of those drugs.