User:Bacteriaburst/Cytochrome P450
Cytochrome P450
Drug metabolism
[edit]P450s are the major enzymes involved in drug metabolism, accounting for about 75% of the total metabolism.[1] Most drugs undergo deactivation by P450s, either directly or by facilitated excretion from the body. However, many substances are bioactivated by P450s to form their active compounds like the antiplatelet drug clopidogrel and the opiate codeine.
The CYP450 enzyme superfamily comprises 57 active subsets, with seven playing a crucial role in the metabolism of most pharmaceuticals.[2] The fluctuation in the amount of CYP450 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) in phase 1 (detoxification) can have varying effects on individuals, as genetic expression varies from person to person. This variation is due to the enzyme’s genetic polymorphism, which leads to variability in its function and expression. To optimize drug metabolism in individuals, genetic testing should be conducted to determine functional foods and specific phytonutrients that cater to the individual’s CYP450 polymorphism. Understanding these genetic variations can help personalize drug therapies for improved effectiveness and reduced adverse reactions.[3]
Nutritional Modulation of CYP450 Enzymes: Balancing Induction and Inhibition
CYP450 enzymes play a crucial role in metabolic pathways by converting xenobiotics into hydrophilic molecules. The effect of a food as an inducer or inhibitor depends on the dose extracted, making many foods capable of acting as either. For instance, cruciferous vegetables are known to induce CYP1A1 and aid in the upregulation of CYP1B1. These vegetables, along with berries, can also influence estrogen processing in the body. Berries are believed to reduce the activity of CYP1A1, while cruciferous vegetables may boost the activity of CYP1A enzymes over CYP1B1 enzymes.[3]
Clinical studies suggest that resveratrol, found in foods like grapes and red wine, enhances CYP1A1 activity. Conversely, certain berries, especially those containing ellagic acid, may help reduce excessive CYP1A1 activity. Apiaceous vegetables (such as carrots, celery, and parsley) and quercetin (a flavonoid found in many fruits, vegetables, and tea), may also help reduce excessive CYP1A2 activity.[3][4][5]
Other foods that can help induce CYP450 family enzymes include chicory, garlic, rosemary, rooibos tea, and fish oil. However, further research is needed to determine the correct dosage of each to ensure the desired results.[3]
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[edit]References
[edit]- ^ Guengerich FP (January 2008). "Cytochrome p450 and chemical toxicology". Chemical Research in Toxicology. 21 (1): 70–83. doi:10.1021/tx700079z. PMID 18052394. S2CID 17548932. (Metabolism in this context is the chemical modification or degradation of drugs.)
- ^ Bains, Ripudaman K. (2013). "African variation at Cytochrome P450 genes". Evolution, Medicine, and Public Health. 2013 (1): 118–134. doi:10.1093/emph/eot010. ISSN 2050-6201. PMC 3868406. PMID 24481193.
{{cite journal}}: CS1 maint: PMC format (link) - ^ a b c d Hodges, Romilly E.; Minich, Deanna 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: 1–23. doi:10.1155/2015/760689. ISSN 2090-0724.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Peterson, Sabrina; Lampe, Johanna W.; Bammler, Theo K.; Gross-Steinmeyer, Kerstin; Eaton, David L. (2006-09). "Apiaceous vegetable constituents inhibit human cytochrome P-450 1A2 (hCYP1A2) activity and hCYP1A2-mediated mutagenicity of aflatoxin B1". Food and Chemical Toxicology. 44 (9): 1474–1484. doi:10.1016/j.fct.2006.04.010.
{{cite journal}}: Check date values in:|date=(help) - ^ Nishimuro, Haruno; Ohnishi, Hirofumi; Sato, Midori; Ohnishi-Kameyama, Mayumi; Matsunaga, Izumi; Naito, Shigehiro; Ippoushi, Katsunari; Oike, Hideaki; Nagata, Tadahiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Kobori, Masuko (2015-04-02). "Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan". Nutrients. 7 (4): 2345–2358. doi:10.3390/nu7042345. ISSN 2072-6643. PMC 4425148. PMID 25849945.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)