AN ADVANCED SUMMARY OF DETOX MEDICINE

Below is a solid and serious list of major detoxification-related chemicals, enzymes, and transporters, with body sources and when they matter most. 

In biochemistry, detoxification mainly means:

phase I biotransformation, 

phase II conjugation, and

phase III transport/excretion.

1. Glutathione (GSH)

• Body source: Synthesized in most cells, especially liver
• When it matters: Major antioxidant and conjugating molecule; crucial for oxidative stress, drug metabolism, and toxin handling (e.g., acetaminophen)

2. Glutathione S-transferases (GSTs)

• Body source: Enzymes highly expressed in liver, also gut and other tissues
• When it matters: Conjugate electrophilic toxins to glutathione during phase II detoxification

3. Glutathione reductase

• Body source: Present in most tissues
• When it matters: Regenerates reduced glutathione; important when oxidative burden is high

4. N-acetylcysteine (NAC)

• Body source: Not made in large amounts endogenously; used as a precursor supplement
• When it matters: Supports glutathione synthesis; clinically relevant in acetaminophen toxicity and low glutathione states

5. Cysteine

• Body source: From diet and from methionine via transsulfuration
• When it matters: Rate-limiting amino acid for glutathione synthesis under many conditions

6. Methionine

• Body source: Essential amino acid from diet
• When it matters: Supports methylation and sulfur amino acid metabolism

7. S-adenosylmethionine (SAMe)

• Body source: Produced from methionine in cells
• When it matters: Universal methyl donor; important for methylation-dependent detox reactions

8. Folate / 5-methyltetrahydrofolate (5-MTHF)

• Body source: Dietary folate, converted to active forms
• When it matters: One-carbon metabolism and methylation support

9. Vitamin B12

• Body source: Dietary intake, absorbed in ileum with intrinsic factor
• When it matters: Works with folate in methylation and homocysteine metabolism

10. Vitamin B6 (pyridoxal-5-phosphate, P5P)

• Body source: Dietary intake
• When it matters: Needed for transsulfuration and amino acid metabolism

11. UDP-glucuronic acid

• Body source: Made intracellularly from glucose
• When it matters: Donor substrate for glucuronidation

12. UDP-glucuronosyltransferases (UGTs)

• Body source: Enzymes concentrated in liver and intestine
• When it matters: Major phase II enzymes that make compounds more water-soluble

13. Sulfate

• Body source: Derived from diet and sulfur amino acid metabolism
• When it matters: Donor for sulfation reactions

14. Sulfotransferases (SULTs)

• Body source: Liver and many extrahepatic tissues
• When it matters: Important for detoxifying hormones, drugs, and xenobiotics

15. Cytochrome P450 enzymes (CYPs)

• Body source: Mainly liver, also intestine and other tissues
• When it matters: Major phase I oxidation system for drugs and toxins

16. Cytochrome P450 reductase

• Body source: Expressed with CYP systems in microsomes
• When it matters: Transfers electrons to CYP enzymes for oxidation reactions

17. NADPH

• Body source: Generated by pentose phosphate pathway and other metabolism
• When it matters: Required for CYP function and antioxidant recycling

18. Flavin adenine dinucleotide (FAD)

• Body source: Derived from riboflavin (B2)
• When it matters: Cofactor for redox enzymes, including glutathione reductase

19. Flavin mononucleotide (FMN)

• Body source: Also derived from riboflavin (B2)
• When it matters: Important in electron transfer systems

20. Taurine

• Body source: From cysteine metabolism and diet
• When it matters: Conjugation of bile acids; supports bile flow and elimination

21. Glycine

• Body source: Dietary and endogenous synthesis
• When it matters: Amino acid conjugation and glutathione synthesis

22. Glycine N-acyltransferase (GLYAT)

• Body source: Liver mitochondrial enzyme
• When it matters: Conjugates organic acids for urinary excretion

23. Epoxide hydrolase

• Body source: Liver and other tissues
• When it matters: Converts reactive epoxides to less reactive diols

24. Carboxylesterases

• Body source: Liver, intestine
• When it matters: Hydrolyze ester-containing xenobiotics and prodrugs

25. NQO1 (NAD(P)H:quinone oxidoreductase 1)

• Body source: Widely expressed, induced by oxidative stress response
• When it matters: Detoxifies quinones and reduces redox cycling

26. Heme oxygenase-1 (HO-1)

• Body source: Inducible in many tissues
• When it matters: Stress-response enzyme that degrades heme under oxidative stress

27. Superoxide dismutase (SOD)

• Body source: Cytosol, mitochondria, extracellular space
• When it matters: Removes superoxide; supports detox by limiting oxidative injury

28. Catalase

• Body source: Mainly peroxisomes
• When it matters: Breaks down hydrogen peroxide

29. Thioredoxin / Thioredoxin reductase

• Body source: Present in most cells
• When it matters: Maintains redox balance and supports antioxidant defenses

30. ABCB1 (P-glycoprotein)

• Body source: Intestine, liver canalicular membrane, kidney, blood-brain barrier
• When it matters: Pumps xenobiotics out of cells; key phase III transporter

31. ABCC2 (MRP2)

• Body source: Liver canalicular membrane, intestine
• When it matters: Exports glucuronide, glutathione, and sulfate conjugates into bile

32. ABCG2 (BCRP)

• Body source: Intestine, liver, placenta, blood-brain barrier
• When it matters: Efflux of many xenobiotics and metabolites

33. Organic anion transporting polypeptides (OATPs)

• Body source: Liver, intestine, other tissues
• When it matters: Uptake transporters that move compounds into hepatocytes for processing

34. Selenium

• Body source: Dietary micronutrient
• When it matters: Needed for selenoenzymes such as glutathione peroxidase

35. Zinc

• Body source: Dietary micronutrient
• When it matters: Supports many enzymes and antioxidant defenses

36. Magnesium

• Body source: Dietary mineral
• When it matters: ATP-dependent enzymatic reactions, including metabolism and conjugation

37. Molybdenum

• Body source: Dietary trace element
• When it matters: Cofactor for sulfite oxidase and other enzymes

38. Vitamin C

• Body source: Dietary vitamin
• When it matters: Antioxidant regeneration and protection from oxidative stress

39. Vitamin E

• Body source: Dietary fat-soluble vitamin
• When it matters: Protects membranes from lipid peroxidation

40. Alpha-lipoic acid

• Body source: Endogenously synthesized in small amounts
• When it matters: Redox cofactor and antioxidant support

41. Coenzyme Q10

• Body source: Endogenous synthesis and diet
• When it matters: Mitochondrial electron transport and antioxidant defense

42. Heme-containing cytochrome systems

• Body source: Liver microsomes
• When it matters: Oxidative metabolism of drugs and toxins

43. Bile acids

• Body source: Synthesized in liver from cholesterol
• When it matters: Aid excretion of lipophilic compounds via bile

44. Bile salt export pump (BSEP/ABCB11)

• Body source: Liver canalicular membrane
• When it matters: Exports bile acids into bile for elimination

45. Organic cation transporters (OCTs)

• Body source: Liver, kidney
• When it matters: Handle cationic drugs and metabolites

46. Multidrug resistance-associated proteins (MRPs)

• Body source: Liver, kidney, intestine
• When it matters: Export conjugated toxins and metabolites

47. Urea cycle enzymes

• Body source: Liver
• When it matters: Detoxifies ammonia, a major metabolic toxin

48. Ornithine

• Body source: Produced in the urea cycle
• When it matters: Central intermediate in ammonia detoxification

49. Citrulline

• Body source: Produced in the urea cycle and intestine
• When it matters: Nitrogen disposal and ammonia handling

50. Arginine

• Body source: Dietary and endogenous
• When it matters: Urea cycle substrate; supports ammonia detoxification

When these matter most, overall

They matter most during:

• Drug exposure
• Alcohol exposure
• Inflammation and oxidative stress
• Poor nutrition or deficiency states
• High toxin burden
• Liver or kidney impairment
• Fasting or malnutrition
• Acetaminophen overdose
• High xenobiotic exposure
• Increased bilirubin/bile handling demands

Full references

1. Klaassen, C. D. (Ed.). (2013). Casarett & Doull’s Toxicology: The Basic Science of Poisons (8th ed.). McGraw-Hill Education.
2. Nelson, D. L., & Cox, M. M. (2021). Lehninger Principles of Biochemistry (8th ed.). W. H. Freeman.
3. 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
4. Guengerich, F. P. (2008). Cytochrome P450 and chemical toxicology. Chemical Research in Toxicology, 21(1), 70–83. https://doi.org/10.1021/tx700079z
5. Lu, S. C. (2013). Glutathione synthesis. Biochimica et Biophysica Acta, 1830(5), 3143–3153. https://doi.org/10.1016/j.bbagen.2012.09.008
6. 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
7. 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
8. 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
9. Klaassen, C. D., & Aleksunes, L. M. (2010). Xenobiotic, bile acid, and cholesterol transporters: Function and regulation. Pharmacological Reviews, 62(1), 1–96. https://doi.org/10.1124/pr.109.002014
10. 10.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