Cytochrome P450 enzymes are essential for the metabolism of many medications. … Cytochrome P450 enzymes can be inhibited or induced by drugs, resulting in clinically significant drug-drug interactions that can cause unanticipated adverse reactions or therapeutic failures.
What is the role of cytochrome P450?
Background: The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions.
What is the function of cytochrome P450 in phase I metabolism?
Cytochromes P450 (CYPs) are enzymes that oxidize substances using iron and are able to metabolize a large variety of xenobiotic substances. CYP enzymes are linked to a wide array of reactions including and O-dealkylation, S-oxidation, epoxidation, and hydroxylation.
Which CYP450 enzyme is responsible for the majority of drug metabolism?
CYP3A4 is the most abundantly expressed drug metabolizing enzyme in man responsible for the breakdown of over 120 different medications and is thus an important area for study with respect to enzyme based drug interactions.
Which drugs are metabolized by cytochrome P450?
Among the drugs metabolized are sedatives such as midazolam, triazolam and diazepam, the antidepressives amitriptyline and imipramine, the anti-arryhthmics amiodarone, quinidine, propafenone and disopyramide, the antihistamines terfenadine, astemizole and loratidine, calcium channel antagonists such as diltiazem and …
Why is it called cytochrome P450?
Cytochromes P450, a family of heme-containing monooxygenases that catalyze a diverse range of oxidative reactions, are so-called due to their maximum absorbance at 450 nm, ie, “Pigment–450 nm,” when bound to carbon monoxide.
What happens when cytochrome P450 is inhibited?
In some cases, CYP450 inhibition is irreversible. The formation of a stable complex, between a drug and the metabolizing enzyme, is one mechanism that can result in irreversible inhibition. The inhibitor can be a drug or one of its metabolites.
How does cytochrome P450 detoxify?
Cytochrome P450, Detox Enzymes
Protons (H+) are usually delivered from the cofactor NADH or NADPH through specific amino acids in the CYP enzyme, which relay the protons to the active site, where they are essential for a reductive splitting of the oxygen so a single atom can be added to the substrate.
What drugs are metabolized by CYP1A2?
CYP1A2 plays an important role in metabolism of drugs like clozapine, olanzapine, fluvoxamine, haloperidol, theophylline; biotransformation of endogenous compounds like melatonin, bilirubin, estrogens, procarcinogens, aflatoxin B1, and aromatic/heterocyclic amines as well as caffeine (Gunes and Dahl, 2008).