P450enzymen

P450enzymen, commonly called cytochrome P450 enzymes, constitute a large superfamily of heme-containing monooxygenases found in most organisms. They catalyze the insertion of one atom of oxygen into substrates (monooxygenation) while reducing the second oxygen atom to water, with electrons supplied by NADPH via a dedicated reductase system.

In humans, P450 enzymes participate in phase I metabolism, converting lipophilic compounds into more polar products to facilitate excretion. They metabolize drugs, steroids, fatty acids, and xenobiotics, and can activate or detoxify procarcinogens. The most clinically important families include CYP3A, CYP2D6, CYP2C9, and CYP1A2, among others. CYP3A4, in particular, handles a large share of pharmaceutical drugs.

Structure and localization: Most P450 enzymes are membrane-bound, located in the endoplasmic reticulum; a smaller group resides in mitochondria. They share a conserved heme-binding motif and a cysteine ligand that coordinates the iron in the active site.

Nomenclature and diversity: P450 genes are grouped into families (CYP) and subfamilies (CYP2D, CYP2D6, etc.) based on sequence similarity. Humans carry dozens of functional P450 genes and many pseudogenes, with substantial genetic polymorphism.

Regulation and pharmacogenomics: Expression is induced or inhibited by various compounds through nuclear receptors. Genetic polymorphisms affect enzyme activity, producing poor, intermediate, extensive, or ultra-rapid metabolizer phenotypes, which influence drug response and toxicity.

Applications: P450 enzymes are used as biocatalysts in drug development and synthesis due to their regio- and enantioselectivity. Studying P450s remains central to pharmacology, toxicology, and precision medicine.