Cytochrome p450 enzymes

Enzyme family (see enzymes below) which is localized in the smooth endoplasmic reticulum of cells, rarely in mitochondria, and which plays a central role in the detoxification of drugs and foreign substances (drugs, environmental chemicals, steroids, fatty acids) in general. All enzymes carry an iron-containing heme group and catalyze oxigenation processes on fat-soluble substrates under NADPH and oxygen consumption (chemically, the cytochrome P450 enzyme family belongs to the oxy-reductases or their subgroup of monooxygenases, see below. enzymes).

Reaction mechanism: RH+O2 ^+NADPH+H+ = _ROH+H2O+ ^NADP+

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 monooxygenases or mixed oxygenases (phase 1 reaction). In a phase 2 reaction, side groups are coupled to this group (e.g. conjugation with glucuronic acid: glucuronidation, sulphation, acetylation), which makes the substance water-soluble and thus renal. In addition, transformation from inactive substances (prodrugs) can result in drug-like active metabolites.

The main localization is the endoplasmic reticulum of the liver, but they are also found in the skin, genitals, intestines, pancreas, brain, lungs, kidneys and adrenal glands.

Drugs that are metabolized by the same cytochrome can interfere with each other. The speed of metabolization depends on the kinetics of this process (fast and slow metabolizers).

Various drugs can lead to enzyme induction. The greatest risk of interaction is posed by enzyme inducers when drugs are combined. For example, enzyme inducers can lead to a dramatic loss of efficacy of other drugs a few days after the start of therapy or, conversely, lead to intoxication with the co-medication after discontinuation.

Other drugs (e.g. phenobarbital), including phytopharmaceuticals such as St. John's wort, inhibit Cyp3A4. This results in its substrates being broken down more slowly (prolongation of 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 cytochrome genes can also lead to significantly altered pharmacokinetics (slower/accelerated elimination) of certain drugs, with corresponding consequences (see also codeine).

CYP 3A4 (50%), CYP 2D6 (20%) and CYP 2C19 (together 15%) have the largest share in drug metabolism. The cytochromes CYP 2C9, CVYP 2E1, CYP 2A6 and CYP 1A2 account for around 15%.

CYP 3A4 (50%), CYP 2D6 (20%) and CYP 2C19 (together 15%) account for the largest proportion of drug metabolism. The cytochromes CVYP 2E1, CYP 2A6 and CYP 1A2 account for around 15%.

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