Pharmacogenomics Cytochrome P450: What is it?
Hello, everyone! Could you describe the features and functions of the cytochrome P450?
Cytochrome P450 (cytochrome P450-dependent monooxygenase,, CYP) is the general name for the P450 family of enzymes. They belong to the class of hemoproteins, belong to type b cytochromes. Cytochrome P450, bound to carbon monoxide, has a maximum absorption of light at a wavelength of 450 nm, which is why it is named. Cytochromes P450 are found in all kingdoms of living beings without exception - in animals, plants, fungi, bacteria, archaea. These proteins are absent only in obligate anaerobic organisms. About 11,500 proteins of the CYP system have been described. P450 of bacteria and archaea is dissolved in the cytoplasm, in an evolutionary sense it is the most ancient form of cytochrome P450. In eukaryotic organisms, P450s are membrane proteins. The cytochrome P450 system is involved in the oxidation of numerous compounds, both endogenous and exogenous. Enzymes of this group play an important role in the exchange of steroids, bile acids, unsaturated fatty acids, phenolic metabolites, as well as in the neutralization of xenobiotics (drugs, poisons, drugs).
Cytochrome P450-dependent monooxygenases catalyze the cleavage of various substances through hydroxylation with the participation of the electron donor NADPH and molecular oxygen. In this reaction, one oxygen atom is attached to the substrate, and the other is reduced to water. Enzymes of the cytochrome P450 family, unlike other hemoproteins, usually possessing one type of activity and a strictly defined function, are quite diverse in functions, types of enzymatic activity, and often have low substrate specificity. P450s can exhibit both monooxygenase and oxygenase activity, therefore they are sometimes referred to as oxidases with mixed function. Oxygenase reactions catalyzed by cytochrome P450 are very diverse. One of the most common oxidation reactions of xenobiotics is oxidative dealkylation, accompanied by the oxidation of the alkyl group attached to the N, O, or S atoms. This process occurs in the endoplasmic reticulum (EPR) of hepatocytes. Their substrate specificity is low. They most effectively catalyze the oxidation of non-polar compounds with aliphatic or aromatic rings. P450 of the liver, among other things, is involved in the oxidation of alcohols to the corresponding aldehydes. Hydroxylation of hydrophobic compounds improves their solubility in water and promotes excretion through the kidneys. The set of cytochromes P450 in the ER differs in different people due to genetic characteristics. In this regard, the study of the P450 enzymatic system is of great importance for pharmacology. All other enzymes of the P450 family are localized on the inner mitochondrial membrane, and their catalytic centers are directed towards the matrix. Another common type of reaction is the hydroxylation of cyclic compounds (aromatic, saturated and heterocyclic hydrocarbons). Enzymes of the P450 family can also catalyze hydroxylation reactions of aliphatic compounds, N-oxidation, oxidative deamination, and reduction reactions of nitro compounds. Cytochromes P450 catalyze omega-oxidation of saturated fatty acids, peroxidation of unsaturated fatty acids, hydroxylation of steroid hormones, bile acids and cholesterol, biosynthesis of prostaglandins and vitamin D. Steroidogenic cells contain mitochondria, which are specialized in steroid synthesis. Such mitochondria are usually larger than the mitochondria of cells in other tissues and have a more developed and convoluted surface of the inner membrane].
Thanks, its very interesting information!