CYP1A2

CYP1A2 is a member of the cytochrome P450 superfamily of enzymes that plays a crucial role in drug metabolism and xenobiotic processing in humans. This enzyme is primarily expressed in the liver and is responsible for metabolizing approximately 10-15% of clinically prescribed medications.

The gene encoding CYP1A2 is located on chromosome 15 and contains seven exons. The enzyme is highly inducible, meaning its expression can be significantly increased by exposure to certain substances including cigarette smoke, charbroiled meat, and some plant compounds. This inducibility has important clinical implications, as individuals who smoke or consume large amounts of cruciferous vegetables may metabolize certain drugs more rapidly than others.

CYP1A2 catalyzes the oxidation of various substrates through hydroxylation and demethylation reactions. Key medications metabolized by this enzyme include caffeine, theophylline, clozapine, olanzapine, and several antidepressants. The enzyme also processes endogenous compounds such as melatonin and arachidonic acid metabolites.

Genetic polymorphisms in the CYP1A2 gene contribute to interindividual variability in enzyme activity. The most well-characterized variant is CYP1A2*1F, which affects enzyme induction but not basal activity. Individuals can be classified as poor, intermediate, or extensive metabolizers based on their CYP1A2 activity levels, influencing their response to medications and susceptibility to drug interactions.

Clinically, understanding CYP1A2 function is essential for optimizing drug dosing and avoiding adverse effects. For example, smokers may require higher doses of clozapine due to increased metabolism, while concurrent use of CYP1A2 inhibitors can lead to toxic drug accumulation. The enzyme's activity can be measured through caffeine metabolic ratios or specific probe drug tests, providing valuable information for personalized medicine approaches.