Detoxification Phase 2 - what is Conjugation?

Conjugation means to join and so this process involves adding a specific molecule – chemical groups – to metabolites produced in phase I to make them water soluble and therefore make them less harmful.


Once these metabolites are converted into water-soluble products, they can be easily excreted via kidney and intestine through urine and bile. The nature and method of adding this certain molecule is called pathway. Conjugation has six main pathways which means that in each of these pathways the molecules being added differ according to the metabolite being processed. The six pathways are:

  • Amino acid pathway: the first step in the breakdown of amino acids is the removal of the amino group, and the immediate products are two amino acids, glutamine and glutamate. Other products include Glycine, Taurine, Arginine and Ornithine.
  • Glutathione pathway (Glutathionation): it detoxifies heavy metals. Gluthathione also plays an important role as an antioxidant helping get rid of free radicals.
  • Acetylation pathway: adding the acetyl chemical group
  • Methylation pathway: adding the methyl chemical group
  • Glucuronidation pathway: helps the body to remove unwanted substances including endogenous substances such as bilirubin, certain drugs and other environmental toxins. 
  • Sulfation pathway: includes sulfate activation and metabolism

What nutrients can support phase two detoxification?

Each of these pathways requires the presence of additional nutrients – mostly amino acids – in order for the process to be completed. In the absence of these nutrients the process is impaired and if detoxification phase II is put on hold, a build-up of phase I will grow, leading to inflammation and consequently tissue damage. For efficient phase two detoxification, the liver cells require sulphur-containing amino acids such as taurine and cysteine. The nutrients glycine, glutamine, choline and inositol are also required for efficient phase two detoxification. These nutrients can be found in so many foods that should be incorporated into the dietary habits; for example, eggs, cruciferous vegetables (eg, broccoli, cabbage, Brussels sprouts, cauliflower), raw garlic, onions, leeks and shallots are all good sources of natural sulphur compounds to enhance phase two detoxification. Thus, generally speaking, these foods can be considered to have a “cleansing” action.

As it is shown, each of these pathways deals with different substances and chemical groups. However, some are more important than others. The glutathione pathway mainly processes fat-soluble toxins into water-soluble compounds ready for elimination, and around 60% of the toxins eliminated by bile are processed by the glutathione pathway. The importance of this pathway is that if it to becomes impaired a build-up of fat-soluble toxins will overload the body.

Fat-soluble toxins incorporate themselves into fatty parts of the body where they may stay for years. The brain and the endocrine glands are fatty organs as well, and are common sites for fat-soluble toxins to accumulate. This may result in symptoms of brain dysfunction and hormonal imbalances, such as infertility, breast pain, menstrual disturbances, adrenal gland exhaustion and early menopause. This pathway is therefore often considered to be the most important throughout phase II of the detoxification process.

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