Support and Enhancement of Phase II Detoxification Pathways Using Foods, Food-Derived Components and Nutrients

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Phase II Detoxification Pathways

There are 6 Phase II detoxification pathways in the body.  Each conjugation pathway serves a specific purpose of detoxifying certain toxins and requires specific nutrients to function.  These 6 detoxification pathways include:

  • Glutathione conjugation
  • Methylation
  • Sulfation
  • Acylation/Glycation
  • Acetylation
  • Glucuronidation

These 6 conjugation pathways are found primarily in the liver and in various other locations within the body:

Locations of Phase 2 Conjugation
Pathways

Conjugation System Location in Body
Acylation/Glycation conjugation liver, kidney
Glutathione conjugation liver, kidney
Glucuronidation liver, kidney, intestine, lung, skin, prostate,
brain
Acetylation liver, lung, spleen, gastric mucosa, RBCs,
lymphocytes
Sulfation liver, kidney, intestine
Methylation liver, kidney, lung,
CNS

Source:  Liston HL, Markowitz JS, DeVane CL, (October 2001). “Drug glucuronidation in clinical psychopharmacology”. J Clin Psychopharmacol 21 (5): 500–15.doi:10.1097/00004714-200110000-00008. PMID 11593076

Phase II Conjugation Enzymes

After a toxin (xenobiotic) has gone through the process of becoming hydrophilic (water-soluble) through reactions overseen by Phase I enzymes, its intermediate molecules are then conjugated with endogenous hydrophilic enzymes.  These endogenous enzymes include:  1

  • glucuronic acid (glucuronyl transferases)
  • sulfate (sulfotransferases)
  • glutathione (glutathione transferases)
  • amino acids (amino acid transferases)
  • acetyl group (N-acetyl transferases)
  • methyl group (N- and O-methyltransferases)

These enzymatic reactions result in an increase in the hydrophilicity of the metabolite leading to enhanced excretion in the bile and/or urine.

The modulation of phase II enzymes by food-based bioactive compounds can support and enhance the Phase II process, especially when there are issues with:

  • genetic polymorphisms that inhibnit Phase II
  • high toxic burden due to chronic exposure to environmental pollutants
  • overactive Phase I activity
  • hormonal imbalance

Each of the 6 Phase II pathways are supported and enhanced by various foods, food-derived components and nutrients.

Amino Acid Conjugation:  Acylation/Glycation

In acylation/glycation, toxins are attached to amino acids, especially glycine. A low protein diet can inhibit acylation/gylcation.  Acylation/glycation detoxifies compounds like benzoate, aspirin and toluene (a widely used industrial solvent).

AminoAcidConjugation

Glucuronidation

Glucuronic acid is a metabolite of glucose that can be attached to toxins. This pathway is used as a back-up for sulfation or acylation/glycination. It is used to eliminate chemical and bacterial toxins, excess steroidal hormones (like estrogen), toxins from fungal infections and a variety of chemical toxins such as nitrosamines, aromatic amines, alcohols and phenols.

Glucuronidation

Glutathione Conjugation

Attaching toxins to glutathione helps to detoxify and eliminate poisons in the liver, lungs, intestines and kidneys. Glutathione helps the body get rid of a wide variety of chemical compounds including aromatic disulphides, paththalene and anthracene.

GlutathioneNutrients

Glutathione

Methylation

Methylation attaches toxins to the amino acid methionine. This process occurs in every cell of the body and helps the body get rid of excess hormones and neurotransmitters, including steroidal hormones like estrogen, adrenaline, dopamine, melatonin, histamine and serotonin. It also helps eliminate homecysteine, a compound associated with increased risk of heart disease. A variety of chemicals (amines, phenols, etc.) are also eliminated through methylation.

Methylation

Sulfation

Sulfation eliminates toxins by attaching them to sulphate. This is the principle pathway for eliminating excess neurotransmitters, several drugs (including acetaminophen, some food additives and toxins from intestinal bacteria. It also removes many forms of environmental toxins. Reduced sulfation may be involved in Parkinson’s disease, Alzheimer’s disease and other nervous system disorders and in environmental illness.

Sulfation

Acetylation

Acetylation involves attaching acetyl co-A to toxins for elimination. People who are chemically sensitive are usually slow acetylators. Slow acetylation enhances the toxicity of drugs because it prolongs their life span in the body. Acetylation is used to eliminate excess histamine, serotonin, sulfa drugs, PABA and chemicals like sulphur amides and hydranzines.

Acetylation

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Glutathione conjugation (page 1)

Glutathione conjugation  (page 2)

Methylation

Sulfation

Acylation/Glycation

Acetylation

Glucuronidation