W-3 Enzymes

1

CYP1A2 ENZYME 6

CYP 1A2 enzyme

What is the CYP1A2 enzyme?

The CYP1A2 enzyme is one of the major and essential enzymes of the CYP 450 (cytochrome P450) group or family (Guo et al., 2021). The CYP 450 family consists of various enzymes such as the CYP1A2 that are involved in the metabolism of various drugs (Guo et al., 2021). As such, the CYP1A2 is an essential detox enzyme that assists in breaking down the toxic chemicals, hormones, drugs, and other products leading to their elimination from the body (Saiz-Rodríguez et al., 2019). This enzyme occurs mainly in the liver, and it comprises about thirteen percent of the CYP enzymes (Guo et al., 2021). However, it is also found at lower levels in the lungs, intestines, brain, and pancreas (Guo et al., 2021). As such, this enzyme is inducible in various parts of the body that include; the liver, gastrointestinal tract, pancreas, brain, and lungs.

Importance of the CYP1A2

The CYP1A2 is one of the major and essential drug-metabolizing enzymes in the liver that assists in breaking down the toxic chemicals, hormones, drugs, and other products in the body, which helps in their elimination from the body (Saiz-Rodríguez et al., 2019). For instance, it contributes to a significant percentage of the oxidative metabolism of several clinically relevant drugs (Saiz-Rodríguez et al., 2019).

This enzyme is involved in the metabolism of various clinically relevant drugs that include Imipramine, Clozapine, Mexiletine, Cyclobenzaprine, and Theophylline. As such, the CYP1A2 usually helps in the breakdown and elimination of these drugs from the body. Additionally, it is recognized as the major metabolizing enzyme for caffeine (Koonrungsesomboon et al., 2018). This enzyme is also involved in the metabolism of various hormones like estrogens and Melatonin (Guo et al., 2021). It also helps in the breakdown of various toxic substances like aflatoxin B1 and polycyclic aromatic hydrocarbons. Overall, this enzyme is essential for the processing of various products and hormones and the elimination of toxic substances from the body. According to Koonrungsesomboon et al. (2018), the CYP1A2 enzyme is essential for dosing of various antipsychotics and evaluation of their efficacy as well as adverse drug reactions.

What does it do in the human body?

This enzyme plays a significant role in the metabolism of various medications like Ropinirole, Theophylline, Olanzapine, Haloperidol, and Clozapine (Guo et al., 2021). Additionally, it helps in the biotransformation of various endogenous compounds such as melatonin, aflatoxin B1, estrogens, heterocyclic/aromatic amines, bilirubin, and procarcinogens (Guo et al., 2021). As such, this enzyme helps in the breakdown of various toxic substances, hormones, drugs as well as other products, which helps in their elimination from the body (Guo et al., 2021). However, the CYP1A2 enzyme may activate some of the cancer-causing agents like aflatoxin B1 and heterocyclic/aromatic amines leading to the development of cancer. As such, decreased or increased activity of this enzyme is associated with an increased risk for cancer.

What are the common medications that inhibit the enzyme, including any substrates?

The medications that usually minimize or decrease the activity of this enzyme are referred to as the CYP1A2 inhibitors (Hakkola et al., 2020). Among the common medications that inhibit this enzyme include Atazanavir, Zileuton, Ciprofloxacin, Tacrine, Enoxacin, Cimetidine, and Artemisinin (Hakkola et al., 2020). For instance, Enoxacin, Ciprofloxacin, and Fluvoxamine are classified as some of the strong inhibitors of this enzyme (Hakkola et al., 2020). The moderate inhibitors of this enzyme include Mexiletine and Methoxsalen while the weak inhibitors include Cimetidine and Acyclovir (Hakkola et al., 2020). On the other hand, the medications that are usually metabolized by this enzyme are referred to as the CYP1A2 substrates (Hakkola et al., 2020). Some of the common CYP1A2 substrates include Olanzapine, Ropinirole, Clozapine, Alosetron, Flutamide, Theophylline, Mirtazapine, and Rasagiline (Hakkola et al., 2020). For instance, some of the sensitive substrates include Duloxetine, Alosetron, and Tizanidine while some of the medications or substrates that are moderately sensitive include Theophylline and Clozapine (Hakkola et al., 2020).

What are the important medication restrictions regarding this enzyme?

The CYP1A2 inhibitors usually minimize the metabolism as well as the efficacy or effectiveness of the substrate medications (Hakkola et al., 2020). The medications that inhibit this enzyme are associated with a high likelihood of increasing the concentrations of the substrate medications in the plasma that may lead to the occurrence of adverse outcomes (Hakkola et al., 2020). Thus, it is necessary to avoid the prescription and use of substrate medications alongside the associated inhibitors to prevent the occurrence of drug-drug interactions or adverse outcomes. For instance, it is necessary to avoid the prescription and use of clozapine or theophylline alongside the CYP1A2 inhibitors like fluvoxamine and ciprofloxacin. Additionally, the use of tizanidine and fluvoxamine usually leads to increased concentrations of Tizanidine in the plasma that results in the occurrence of adverse outcomes (Hakkola et al., 2020). Therefore, it is necessary to avoid the concurrent use of these medications to prevent the occurrence of adverse outcomes. Overall, the increased involvement of this enzyme in drug interactions underscores the need to promote appropriate use of the medications that are metabolized by this enzyme. Thus, it is necessary to avoid the concurrent use of substrates like Tizanidine, Theophylline, Olanzapine, and Clozapine together with potent inhibitors like Enoxacin, Ciprofloxacin, and Fluvoxamine to minimize the occurrence of adverse outcomes (Hakkola et al., 2020).

References

Guo, J., Zhu, X., Badawy, S., Ihsan, A., Liu, Z., Xie, C., & Wang, X. (2021). Metabolism and Mechanism of Human Cytochrome P450 Enzyme 1A2. Current Drug Metabolism, 22(1), 40-49.

Hakkola, J., Hukkanen, J., Turpeinen, M., & Pelkonen, O. (2020). Inhibition and induction of CYP enzymes in humans: an update. Archives of toxicology, 1-52.

Koonrungsesomboon, N., Khatsri, R., Wongchompoo, P., & Teekachunhatean, S. (2018). The impact of genetic polymorphisms on CYP1A2 activity in humans: a systematic review and meta-analysis. The pharmacogenomics journal, 18(6), 760-768.

Saiz-Rodríguez, M., Ochoa, D., Belmonte, C., Román, M., Vieira de Lara, D., Zubiaur, P., ... & Abad-Santos, F. (2019). Polymorphisms in CYP1A2, CYP2C9 and ABCB1 affect agomelatine pharmacokinetics. Journal of Psychopharmacology, 33(4), 522-531.