CYP450

Cytochrome P450

The Cytochrome P450 (CYP450) enzymes are a large and diverse group of enzymes that play a crucial role in the metabolism of drugs and the synthesis of cholesterol, steroids, and other lipids. These enzymes are found in the liver and are involved in the oxidation of organic substances.

Structure and Function

Cytochrome P450 enzymes are heme-thiolate proteins that catalyze the oxidation of organic substances. They are named for their spectral properties, specifically the absorption peak at 450 nm when bound to carbon monoxide. The CYP450 enzymes are involved in the metabolism of a wide variety of substrates, including drugs, toxins, and endogenous compounds.

The primary function of CYP450 enzymes is to catalyze the oxidation of organic molecules, which often results in increased solubility and excretion of these compounds. This process is essential for the detoxification of xenobiotics and the metabolism of drugs.

Genetic Variability

The CYP450 enzyme family is highly polymorphic, meaning there is significant genetic variability among individuals. This variability can affect how different people metabolize drugs, leading to differences in drug efficacy and the risk of adverse effects. Some of the most well-known polymorphisms occur in the CYP2D6, CYP2C9, and CYP2C19 genes.

Clinical Significance

CYP450 enzymes are of great clinical importance because they are involved in the metabolism of many drugs. Understanding the activity of these enzymes can help predict drug interactions and individual responses to medications. For example, inhibitors or inducers of CYP450 enzymes can alter the metabolism of drugs, leading to increased toxicity or decreased efficacy.

Common CYP450 Enzymes

Some of the most important CYP450 enzymes in drug metabolism include:

• CYP3A4: Responsible for the metabolism of approximately 50% of all drugs.
• CYP2D6: Metabolizes many antidepressants and antipsychotic medications.
• CYP2C9: Involved in the metabolism of nonsteroidal anti-inflammatory drugs (NSAIDs) and warfarin.
• CYP2C19: Metabolizes proton pump inhibitors and some antiepileptic drugs.

Drug Interactions

Drug interactions involving CYP450 enzymes can occur when one drug affects the metabolism of another. This can happen through enzyme inhibition or induction. For example, grapefruit juice is a known inhibitor of CYP3A4, which can lead to increased levels of certain drugs and potential toxicity.

Also see

• Drug metabolism
• Enzyme induction
• Enzyme inhibition
• Pharmacogenomics
• Xenobiotic