Mar 06, 2024
WHAT IS DETOXIFICATION?
The liver is a center where physiological and biochemical events occur in our body. Among all these functions, the most important function of the liver is detoxification (Sheriock, 2011). The liver carries out detoxification processes with enzymes. These enzymes transform toxic chemicals into water-soluble substances, and the products resulting from this transformation are excreted from the body with bile and urea as the end product (Liska, 1998; Sheriock, 2011).
Detoxification consists of 2 main stages: phase 1 and phase 2. In Phase 1 of the detoxification process, the liver converts toxic substances into intermediate metabolites that are more toxic than the original. In Phase 2, the second stage of detoxification, these more toxic intermediate metabolites are converted into more harmless and water-soluble substances by using enzymes to be excreted with bile or urea (Liska, 1998).
Detoxification Phase 1 Enzymes and Genes
Phase I generally constitutes the first enzymatic defense system against toxins. As a result of this stage in detoxification, reactive molecules that may be more toxic than the first molecule are produced (Vermeulen, 1996). In phase 1, oxidation, reduction and hydrolysis reactions occur by various enzyme classes (Grant, 1991).
Cytochrome P450 (CYP450)
The cytochrome P450 superfamily (CYP450) generally metabolizes xenobiotics, steroid hormones and drugs. It is found mainly in the liver, but also in enterocytes, kidneys, lung and even the brain (Danielson, 2002).
Any variability in the number and structure of CYP450 enzymes changes the individual's response to toxins, either positively or negatively (Danielson, 2002). Genetic polymorphisms of these CYP450 genes alter the expression and function of the enzymes. This situation causes people to be more advantageous or disadvantaged in some situations (Hodges & Minich, 2015). For example, an individual's ability to metabolize 90% of currently used drugs depends largely on the genetic expression of these enzymes (Chen et al., 2011).
What is the CYP1A1 gene?
CYP1A1 is a member of the CYP450 family. They play a role in the transformation of toxic substances (Polycyclic aromatic hydrocarbons (PAHs) and estrogen metabolism. CYP1A1 is one of the most important genes responsible for the bioactivation of tobacco carcinogenic substances, including nitrosamines and benzopyrenes, as well as alcohol metabolism (Bandeira et al., 2022).
What is the CYP1A2 Gene?
CYP1A2 is part of the CYP450 family; They play an important role in the metabolism of caffeine, drugs and some hormones (e.g. melatonin) (Hodges & Minich, 2015). Gender, smoking, ethnicity, food compounds, drugs, and genetic variations all affect CYP1A2 activity. More than 40 SNPs have been found in the CYP1A2 gene, and one of the most extensively studied is rs762551. CYP1A2 AA homozygotes are generally classified as “extensive metabolizers,” while individuals with the CC/CA genotype are classified as “poor metabolizers” (Nikrandt et al., 2022).
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Phase 1- Cytochrome P450(CYP450) |
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Genes |
rs-code |
Minor allele |
Minor Allele Description |
Reference |
|
CYP1A1 |
rs1048943 |
C |
Increased relative risk for high enzyme activity. |
|
|
CYP1A2 |
rs12720461 |
T |
Increased relative risk for decreased enzyme activity. |
|
|
CYP1A1 |
rs2472297 |
T |
Increased relative risk for high enzyme activity. |
|
|
CYP1A2 |
rs762551 |
A |
Increased relative risk for high enzyme activity. |
|
The table above includes CYP genes and polymorphisms. These polymorphisms are genetic variants that may predispose a person to certain conditions or protect a person against certain conditions. Studies on these genes are as follows; Individuals with the CYP1A1 gene rs2472297 polymorphism were associated with lower plasma caffeine levels than other individuals. That means, they metabolized caffeine faster (Cornelis et al., 2015). CYP1A1 rs1048943 Ile462Val polymorphism was found to increase the risk of cervical cancer (Wang et al., 2017). Individuals with the CYP1A2 rs762551 polymorphism have been found to have an overall increased risk of cancer (Wang et al., 2012). Individuals with the CYP1A2 rs12720461 polymorphism have been shown to have a high risk of breast, lung and ovarian cancer (Szalai et al., 2014).
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CYP1A1 Inducers |
CYP1A1 Inhibitors |
CYP1A2 Inducers |
CYP1A2 Inhibitors |
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Green tea |
Sulforaphane |
Green tea |
Sulforaphane |
|
|
Quercetin |
|
Quercetin |
|
|
Curcumin |
|
Curcumin |
References
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Chen, Q., Zhang, T., Wang, J.-F., & Wei, D.-Q. (2011). Advances in human cytochrome p450 and personalized medicine. Current Drug Metabolism, 12(5), 436-444.
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Grant, D. M. (1991). Detoxification Pathways in the Liver. In R. A. Harkness, R. J. Pollitt, & G. M. Addison (Eds.), Journal of Inherited Metabolic Disease (pp. 421-430). Springer Netherlands. https://doi.org/10.1007/978-94-011-9749-6_2
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Liska, D. J. (1998). The detoxification enzyme systems. Altern. Med. Rev, 187-198.
Nikrandt, G., Mikolajczyk-Stecyna, J., Mlodzik-Czyzewska, M., & Chmurzynska, A. (2022). Functional single-nucleotide polymorphism (rs762551) in CYP1A2 gene affects white coffee intake in healthy 20- to 40-year-old adults. Nutrition Research, 105, 77-81. https://doi.org/10.1016/j.nutres.2022.06.003
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Wang, L.-N., Wang, F., Liu, J., Jin, Y.-H., Fang, C., & Ren, X.-Q. (2017). CYP1A1 Ile462Val Polymorphism Is Associated with Cervical Cancer Risk in Caucasians Not Asians: A Meta-Analysis [Original Research]. Frontiers in Physiology, 8. https://doi.org/10.3389/fphys.2017.01081