Glutathione (GSH)
- N-acetylcysteine (NAC)
- Cysteine
- Glycine
- Glutamate
- Methionine
- S-adenosylmethionine (SAMe)
- Serine
- Taurine
- UDP-glucuronic acid
- Glucuronic acid
- Sulfate
- Sulfur-containing amino acids
- Vitamin B2 (riboflavin)
- Vitamin B3 (niacin)
- Vitamin B6 (pyridoxal phosphate)
- Vitamin B9 (folate)
- Vitamin B12 (cobalamin)
- Vitamin C (ascorbate)
- Vitamin E (tocopherols)
- Selenium
- Zinc
- Magnesium
- Molybdenum
- Alpha-lipoic acid
- Coenzyme Q10
- NADPH
- Flavin adenine dinucleotide (FAD)
- Flavin mononucleotide (FMN)
- Heme iron-containing cytochrome P450 enzymes
More science: major detox pathways
Phase I
- Oxidation
- Reduction
- Hydrolysis
- Mainly catalyzed by cytochrome P450 enzymes
- Often makes compounds more reactive, so Phase II is important afterward
Phase II
- Glutathionation
- Glucuronidation
- Sulfation
- Acetylation
- Methylation
- Amino acid conjugation
- Glycine conjugation
- Taurine conjugation
Phase III
- Transporters remove conjugated compounds from cells into bile or urine
- Important transporters include:
- P-glycoprotein (ABCB1)
- MRP2 (ABCC2)
- BCRP (ABCG2)
Key biochemical notes
- NADPH is required to keep antioxidant systems working and supports reductive metabolism.
- FAD and FMN are essential for flavoproteins involved in redox reactions.
- UDP-glucuronic acid is the activated donor for glucuronidation.
- Sulfate is needed for sulfation reactions.
- Glutathione is the major intracellular thiol antioxidant and a major conjugating molecule.
- Methionine/folate/B12/B6 support methylation and one-carbon metabolism.
- Taurine and glycine are important for conjugating bile acids and certain xenobiotics.
Full references
- Klaassen, C. D. (Ed.). (2013). Casarett & Doull’s Toxicology: The Basic Science of Poisons (8th ed.). McGraw-Hill Education.
- Nelson, D. L., & Cox, M. M. (2021). Lehninger Principles of Biochemistry (8th ed.). W. H. Freeman.
- Zanger, U. M., & Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics, 138(1), 103–141. https://doi.org/10.1016/j.pharmthera.2012.12.007 (opens in new tab)
- Guengerich, F. P. (2008). Cytochrome P450 and chemical toxicology. Chemical Research in Toxicology, 21(1), 70–83. https://doi.org/10.1021/tx700079z (opens in new tab)
- Lu, S. C. (2013). Glutathione synthesis. Biochimica et Biophysica Acta, 1830(5), 3143–3153. https://doi.org/10.1016/j.bbagen.2012.09.008 (opens in new tab)
- DeLeve, L. D., & Kaplowitz, N. (2014). Glutathione metabolism and its role in hepatotoxicity. Pharmacology & Therapeutics, 109(1–2), 131–149. https://doi.org/10.1016/j.pharmthera.2005.01.010 (opens in new tab)
- Tukey, R. H., & Strassburg, C. P. (2000). Human UDP-glucuronosyltransferases: Metabolism, expression, and disease. Annual Review of Pharmacology and Toxicology, 40, 581–616. https://doi.org/10.1146/annurev.pharmtox.40.1.581 (opens in new tab)
- Stipanuk, M. H. (2004). Sulfate, transsulfuration, and taurine metabolism in health and disease. Advances in Experimental Medicine and Biology, 566, 87–107. https://doi.org/10.1007/0-387-26206-7_5 (opens in new tab)
- Townsend, D. M., Tew, K. D., & Tapiero, H. (2003). The importance of glutathione in human disease. Biomedicine & Pharmacotherapy, 57(3–4), 145–155. https://doi.org/10.1016/S0753-3322(03)00043-X (opens in new tab)
- Hayes, J. D., & Dinkova-Kostova, A. T. (2014). The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends in Biochemical Sciences, 39(4), 199–218. https://doi.org/10.1016/j.tibs.2014.02.002 (opens in new tab)