Our bodies are exposed daily to toxic compounds that must be processed and eliminated. These compounds, called xenobiotics, can be endogenous (produced in the body as by-products of metabolism) or exogenous (originating outside the body), like medications and environmental and dietary toxins. The body is a fantastic machine equipped with detoxification organs that carry out an intricate process called biotransformation. It neutralizes and removes these compounds, preventing them from harming us and keeping the body in homeostasis (Crinnion & Pizzorno, 2018). This blog will dive deep into the biotransformation process of xenobiotics, teaching you all you need to know about its various phases. We will also cover the nutrients and coenzymes that the body that support your body’s detoxification pathways.
What Are Xenobiotics?
Xenobiotics are toxic compounds from natural sources like plants, fungi, or animals or man-made sources like medications, pesticides, and chemicals. These compounds are primarily detoxified in the liver, which breaks them into safer metabolites excreted through the urine or the bile (Crinnion & Pizzorno, 2018).
The detoxification process comprises three phases:
- Phase I: Hydrolysis, Reduction, and Oxidation
- Phase II: Conjugation
- Phase III: Transport
Phase I: Preparing Xenobiotics for Elimination
Phase I of biotransformation breaks down xenobiotics through hydrolysis, reduction, and oxidation, transforming them into more water-soluble metabolites. These reactions make these compounds easier to eliminate by introducing or exposing them to functional groups. However, some metabolites are made more toxic and will only be neutralized once they progress to Phase II.
Hydrolysis:
Hydrolysis uses water to break chemical bonds, converting complex xenobiotics into simpler compounds that will be either processed for elimination or recycled for other functions (Phang-Lyn & Llerena, 2023).
Reduction:
During reduction, NADH or NADPH act as reducing agents by donating electrons or hydrogen atoms to xenobiotics, causing them to become less oxidized (Phang-Lyn & Llerena, 2023).
Oxidation:
Oxidation, however, involves the loss of electrons or hydrogen atoms. Cytochrome P450 (CYP) enzymes are critical in oxidation, transforming hydrophobic compounds into hydrophilic metabolites. The oxidation of alcohol into aldehydes and acids, which detoxifies dangerous compounds like ethanol, is an excellent example of oxidation (Phang-Lyn & Llerena, 2023).
As stated above, Phase I reactions are an essential part of the detoxification process, but they sometimes lead to more toxic metabolites than the original compounds. This is where Phase II comes into play.
Phase II: Conjugation Reactions for Elimination
When xenobiotics are not entirely excreted after Phase I, they enter the Phase II detoxification pathway and undergo conjugation reactions. In Phase II, the body utilizes glutathione, sulfate, or glucuronic acid to neutralize and increase the xenobiotics’ water solubility for excretion.
Glucuronidation:
Glucuronidation is mediated by UDP-glucuronosyltransferases (UGTs), which attach glucuronic acid to the toxin, boosting its solubility and making it easier to excrete through bile or urine (Wang et al., 2021).
Sulfation and Methylation:
Sulfation and methylation are other conjugation reactions that involve adding different functional groups (sulfate, methyl) to promote the elimination of toxins. These processes help our body detoxify hormones, medications, and other toxins.
Acetylation, Glutathione Conjugation, and Amino Acid Conjugation:
Other critical reactions in Phase II detoxification include acetylation, glutathione conjugation, and amino acid conjugation. Each reaction involved adding different functional groups (acetyl, which promotes the metabolism of drugs and environmental toxins; glutathione, which detoxifies ROS, heavy metals, and other toxins; and amino acids like taurine, glutamic acid, and glycine).
Phase III: Transporting Xenobiotics Out of the Body
Once the xenobiotic has been conjugated, Phase III transports them out of the cells via efflux transporters like P-glycoprotein that move the metabolites into the urine or bile for excretion (Phang-Lyn & Llerena, 2023). Phase III is critical to maintaining homeostasis and preventing the harmful effects of toxin bioaccumulation.
Genetic Factors in Detoxification
Understanding that biotransformation is very individualistic and that genetic polymorphisms can greatly influence detoxification enzymes like the CYP family of enzymes or UGTs is essential. Genetic variances affect how an individual metabolizes toxins. For example, people with specific variants of the CYP2D6 gene can be slow metabolizers of certain medications, which causes them to experience side effects and toxicity (Zhao et al., 2021). That is why utilizing a personalized approach to detoxification is essential.
Nutritional Support for Biotransformation
Diet is foundational to supporting biotransformation; proper nutrients can optimize detoxification capacity and protect the liver. Our diet can supply the body with coenzymes and nutrients critical for Phase I and II detoxification. For example, foods high in vitamin B3 (niacin), like fish, meat, and whole grains, help us maintain adequate levels of NADH/NADPH, critical for the reduction reaction. Foods high in vitamin B5 (pantothenic acid), like eggs, avocados, and legumes, can help optimize Coenzyme A levels, a nutrient critical for oxidative and fatty acid metabolism. Glutathione is a critical player in Phase II conjugation reactions. In order to boost glutathione levels, we want to incorporate foods rich in sulfur-containing amino acids, such as garlic, onions, and cruciferous vegetables, as well as foods high in N-acetyl cysteine like chicken, turkey, yogurt, cheese, eggs, sunflower seeds, and legumes. Lastly, including foods rich in antioxidant vitamins C and E, like citrus fruits, leafy greens, nuts, and seeds, can help protect cells from the damage of oxidative stress formed during biotransformation.
Liver Health and Lifestyle Choices
Remember that the liver is the critical player in the detoxification process, so it is crucial to support liver function and minimize factors that can impair detox capacity, like alcohol consumption, poor dietary choices, and medications. To maintain liver health, it is essential to stay hydrated, limit alcohol consumption, avoid processed foods, and eat a diet rich in antioxidants, like the Mediterranean diet, which promotes the consumption of dark leafy greens, colorful vegetables and fruits, legumes, nuts and seeds, healthy fats, and lean sources of protein. Herbs like milk thistle and dandelion root can also support liver function (George et al., 2018).
Conclusion: Enhancing Biotransformation for Optimal Health
Biotransformation is a complex, fascinating process that allows our body to process and excrete toxic compounds safely. Now that you understand how the body detoxifies xenobiotics, you can better support these pathways. Eat a diet high in antioxidants and coenzymes needed to support Phase I and Phase II liver detox, stay hydrated, reduce alcohol, and take liver-supporting supplements. This holistic approach will significantly enhance your body’s detoxification, health, and well-being.
References
Crinnion, W. J., & Pizzorno, J. E., Jr. (2018). Clinical Environmental Medicine: Identification and Natural Treatment of Diseases Caused by Common Pollutants. Elsevier.
George, E. S., Forsyth, A., Itsiopoulos, C., Nicoll, A. J., Ryan, M., Sood, S., Roberts, S. K., & Tierney, A. C. (2018). Practical Dietary Recommendations for the Prevention and Management of Nonalcoholic Fatty Liver Disease in Adults. Advances in nutrition (Bethesda, Md.), 9(1), 30–40. https://doi.org/10.1093/advances/nmx007
Hodges, R. E., & Minich, D. M. (2015). Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application. Journal of nutrition and metabolism, 2015, 760689. https://doi.org/10.1155/2015/760689
Phang-Lyn, S., & Llerena, V. A. (2023, August 14). Biochemistry, biotransformation. StatPearls – NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK544353/
Zhao, M., Ma, J., Li, M., Zhang, Y., Jiang, B., Zhao, X., Huai, C., Shen, L., Zhang, N., He, L., & Qin, S. (2021). Cytochrome P450 Enzymes and Drug Metabolism in Humans. International journal of molecular sciences, 22(23), 12808. https://doi.org/10.3390/ijms222312808
