Cytochrome P-450

Cytochrome P-450

Cytochrome P-450 (CYP450) is 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. The name "cytochrome P-450" is derived from the fact that these enzymes contain a heme group and exhibit a characteristic absorption peak at 450 nm when reduced and bound to carbon monoxide.

Structure and Function

Cytochrome P-450 enzymes are heme-thiolate proteins that catalyze the oxidation of organic substrates. The active site of these enzymes contains a heme iron, which is essential for their catalytic activity. The general reaction catalyzed by CYP450 enzymes is:

RH + O₂ + NADPH + H⁺ → ROH + H₂O + NADP⁺

where RH is the substrate, and ROH is the oxidized product.

CYP450 enzymes are involved in the metabolism of a wide variety of xenobiotics, including drugs, environmental chemicals, and endogenous compounds. They are responsible for the phase I metabolism of drugs, which often involves the introduction of a hydroxyl group into the substrate, making it more polar and thus more easily excreted from the body.

Isoforms

There are many different isoforms of cytochrome P-450, each with a specific substrate specificity. Some of the most important human CYP450 enzymes include:

• CYP3A4: The most abundant CYP450 enzyme in the liver, responsible for the metabolism of approximately 50% of all drugs.
• CYP2D6: Involved in the metabolism of many drugs, including antidepressants and antipsychotics.
• CYP2C9: Metabolizes nonsteroidal anti-inflammatory drugs (NSAIDs) and some oral hypoglycemic agents.
• CYP1A2: Involved in the metabolism of caffeine and some antipsychotic drugs.

Clinical Significance

Cytochrome P-450 enzymes are of great clinical importance due to their role in drug metabolism. Variations in CYP450 enzyme activity can lead to differences in drug efficacy and toxicity among individuals. Genetic polymorphisms in CYP450 genes can result in poor, intermediate, extensive, or ultra-rapid metabolizer phenotypes, affecting drug dosing and response.

Drug interactions involving CYP450 enzymes are common. For example, some drugs can inhibit or induce the activity of specific CYP450 enzymes, leading to altered plasma levels of co-administered drugs. This can result in therapeutic failure or increased risk of adverse effects.

Research and Applications

Research on cytochrome P-450 enzymes continues to be an active area of study, with implications for personalized medicine, drug development, and toxicology. Understanding the specific roles and regulation of different CYP450 isoforms can aid in predicting drug interactions and individual responses to therapy.

Also see

• Drug metabolism
• Enzyme induction
• Pharmacogenomics
• Heme
• Liver function

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