CYP2D6 Enzyme

Answer

I-O: CYP2D6 Enzyme

CYP2D6 Enzyme also known as Cytochrome P450 2D6 is an enzyme that is expressed primary in the liver as well as some areas of the central nervous system such as the nigra and substantia (Gopisankar, 2017). The enzyme belongs to the cytochrome P450 mixed-function oxidase system, which is a family of enzymes that contain the heme as a cofactor and that functions as monooxygenases. In specific, Aitchison et al. (2019) argue that CYP2D6 Enzyme represents 3 percent of the hepatic CYP content. The CYP2D6 enzyme is one of those enzymes that are highly involved in the metabolism of various bodily xenobiotics.

The importance of CYP 2D6 Enzyme is that it is a polymorphic drug-metabolizing enzyme. In specific, the enzyme metabolizes 20-25% of drugs (Gopisankar, 2017). The various substrates of CYP2D6 include opioid analgesics, beta-blockers, antidepressants, as well as antiarrhythmics (Kiss et al., 2018). Compared to other CYP enzymes, CYP2D6 stands out as the one with higher relative inability to be induced through xenobiotic exposure. On the contrary, the enzyme is highly polymorphic containing more than 100 variant alleles (Gopisankar, 2017). Additionally, it has a 200-fold variability in its quest to metabolize at least 100 drugs.

In the body, the CYP 2D6 enzyme metabolizes xenobiotics. Some of the cardiac drugs that are metabolized by CYP 2D6 enzyme include some of the antifungals as well as antiestrogen tamoxifen. Additionally, according to Aitchison et al. (2019), it duplicates genes hence conferring an ultrarapid phenotype metabolizer. Some of the CYP 2D6 subgroups of phenotypes include utrarapid, extensive, and intermediate categories. The subgrouping of the phenotypes is based on the respective numbers of their functional alleles. Compared to other the other P450s, CYP2D6 is the most highly polymorphic with more than 100 variant alleles (Kiss et al., 2018).

Some of the drugs that inhibit the CYP2D6 enzyme include several Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine and fluoxetine (Gopisankar, 2017). Notably, the SSRIs are those forms of antidepressants that serve to affect the levels of serotonin on the brain. Additionally, nonsteroidal anti-inflammatory drugs (NSAID) such as celecoxib inhibit the enzyme (Kiss et al., 2018). Moreover, cinacalcet, quinidine, and terbinafine are known inhibitors of the CYP2D6 enzyme.

The CYP2D6 substrates are mostly found in various antidepressants. Some of these include drugs such as mianserin, doxepin, citalopram and amitriptyline among others (Kiss et al., 2018). Additionally, the enzyme has substrates in antipsychotics including clozapine, perphenazine, and chlorpromazine among other antipsychotic drugs (Aitchison et al., 2019). Although Amphetamines and amphetamine derivatives have also been found to be metabolized by CYP2D6 to a larger degree, it has also been established that they display a major inhibition of CYP2D6 metabolism.

In conclusion, CYP2D6 is one of the enzymes belonging to the Cytochromes P450 (CYP) family. Gopisankar (2017) notes that the CYP family enzymes are those that are produced from the cytochrome p450 gens involved in the metabolism and synthesis of not only chemicals but also molecules in within cells in the liver and the central nervous system. CYP2D6 has been found to be important in the metabolism of various drugs and substrates such as opioid analgesics, beta-blockers, antidepressants, as well as antiarrhythmics.  However, it is inhibited by drugs such as Selective serotonin reuptake inhibitors (SSRIs) and nonsteroidal anti-inflammatory drugs (NSAID).