Cytochrome p450 enzymes

Enzymfamilie (siehe unten Enzyme ), die im endoplasmatischen Retikulum von Zellen lokalisiert ist und eine zentrale Rolle bei der Entgiftung von Arzneimitteln oder Fremdstoffen im Allgemeinen spielt. Alle Enzyme tragen eine eisenhaltige Hämgruppe und katalysieren Oxidationsprozesse auf fettlöslichen Substraten unter NADPH- und Sauerstoffverbrauch (chemisch gehört die Cytochrom P450-Enzymfamilie zu den Oxy-Reduktasen oder ihrer Untergruppe von Monooxygenasen, siehe unten; s.a. Enzyme ).

Cytochrome P450 enzymes can transfer (oxidize) an oxygen atom to the substrate (e.g. a drug) by forming hydroxyl groups and are therefore classified as hydroxylases or referred to as monooxygenase or mixed oxygenase (phase 1 reaction). In a phase 2 reaction, side groups are coupled to this group (e.g. conjugation with glucuronic acid: glucuronidation, sulfation , acetylation), which makes the substance water-soluble and thus suitable for the kidneys. In addition, drug-active metabolites can be formed from inactive substances (prodrugs) by transformation.

Main localization is the endoplasmic reticulum of the liver, but they are also found in skin, genitals, intestine, pancreas, brain, lung, kidney, adrenal gland.

5 of these enzymes (CYP3A4, CYP2D6, CYP2C19, CYP2C9, CYP1A2) metabolize the majority of liver-derived drugs. Drugs metabolized by the same cytochrome may interfere with each other. It depends on the kinetics of this process how fast metabolization occurs (fast and slow metabolizers).

Several drugs can lead to enzyme induction. Other drugs (e.g. phenobarbital), including phytopharmaceuticals such as St. John's wort inhibit Cyp3A4. This causes its substrates to be degraded at a slower rate (prolonging efficacy). CYP2D6 is involved in the metabolism of about every 4th drug (e.g. antiarrhythmics, antidepressants, neuroleptics, antitussives and antiemetics).

Polymorphisms (see pharmacogenetics below) in the coding genes can also lead to significantly altered pharmacokinetics (slowing/acceleration of elimination) of certain drugs, with corresponding consequences (see also under codeine).

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