Cytochrome P450 2D6
| Cytochrome P450 2D6 | ||
|---|---|---|
|
||
| Crystal structure of the human cytochrome P450 2D6 according to 2F9Q | ||
| Properties of human protein | ||
| Mass / length primary structure | 479 amino acids | |
| Secondary to quaternary structure | Homotetramer | |
| Cofactor | Hamm | |
| Identifier | ||
| Gene names | CYP2D6 , CYP2D7AP, CYP2D7BP, CYP2D7P2, CYP2D8P2, CYP2DL1 | |
| External IDs | ||
| Enzyme classification | ||
| EC, category | 1.14.14.1 , monooxygenase | |
| Response type | Hydroxylation | |
| Substrate | RH + FADH + O 2 | |
| Products | ROH + FAD + + H 2 O | |
| Occurrence | ||
| Homology family | Cytochrome P450 | |
| Parent taxon | Creature | |
CYP2D6 is an enzyme from the cytochrome P450 group that is involved in the metabolism of many drugs. It comes in different genetic variants and can therefore affect the way certain medicines work.
genetics
Different variants of the CYP2D6 gene on chromosome 22q13.1 lead to different phenotypes . Depending on the enzyme activity, a distinction is made between:
- "Slow metabolizer" (" poor ")
- "Intermediate metabolizers" ( " intermediate ")
- "Fast metabolizer" (" extensive ")
- " Ultra- fast metabolizer" (" ultrarapid ")
The "fast metabolizer" is the standard variant, whereas the "ultrafast metabolizer" has several copies of the gene for CYP2D6. On the other hand, in the "intermediate metabolizer" the gene function is limited and is almost completely absent in the slow types.
function
CYP2D6 oxidizes or hydroxylates certain substrates (pharmaceuticals) in the liver and activates ( prodrug ) or deactivates them. The dose of a drug therefore often has to be adjusted.
Examples of interactions
- Antidepressants
-
Beta blockers
- Metoprolol
- Propranolol
- Therapeutically, bisoprolol , which is not metabolized via CYP2D6, is therefore often used in an “ultra-fast metabolizer” .
- Neuroleptics
- Opioids
- Dextromethorphan (antitussive, cough suppressant)
- Tamoxifen (prodrug, is converted to endoxifen )
Importance as a diagnostic marker
The presence of antibodies against CYP2D6 is, after viral hepatitis has been ruled out , the characteristic feature of type 2 autoimmune hepatitis . These are also referred to as LKM-1.
Individual evidence
- ↑ CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 . National Institute of Health, USA
- ↑ Birgit Busse: Cytochrome P450 2D6 (CYP2D6) [T88.7] . Center for Human Genetics and Laboratory Medicine, archived from the original on April 12, 2013 ; Retrieved September 26, 2015 .
- ↑ Stephanie Röhm, Andreas Stürer, Jörg Pietsch, Stephanie Läer: Dextromethorphan - a harmless cough suppressant ? In: Deutsche Apotheker Zeitung . No. 31 , 2007, p. 42 ( online - free full text).
- ↑ Ursula Goldmann-Posch: Which CYP2D6 type are you? New findings on the effects and non-effects of tamoxifen . Mamazone.de, Women and Research Against Breast Cancer eV
- ↑ Michael P. Manns , KJ Griffin, KF Sullivan, EF Johnson: LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase. In: Journal of Clinical Investigation . tape 88 , no. 4 , October 1991, p. 1370-1378 , doi : 10.1172 / JCI115443 , PMC 295608 (free full text).