Amino Acid Conjugation Pathway in Metabolic Detoxification: Glycine is the Main Amino Acid

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Phase 1 Biotransformation Process

The primary function of the Phase I biotransformation process is to either:

  • Biotransform a toxic lipophilic compound directly to a more hydrophilic compound so it can be directly excreted in the kidneys (e.g. caffeine). Though, Phase I usually results in only a small amount of direct hydrophilicity and excretion
  • The bulk of Phase I enzymatic activity takes place in the form of altering unwanted compounds in a way as to either expose or introduce a functional group. Functional groups such as: Carboxyl group (–COOH), hydroxyl group (– OH), amino group (-NH2), or sulfhydryl group/thiol (-SH)

In the Phase 1 detoxification process a toxic chemical is converted into a less harmful chemical through various chemical reactions.  Phase 1 is essentially responsible for breaking fat-soluble toxins down and then sending the raw materials to Phase 2 detoxification process.  Phase 2 is the addition or conjugation phase where new substances are added/conjugated to the toxic metabolites produced in Phase 1 in order to make them easier to transport, more stable and/or more functional for the body.

Phase 2 Conjugation Pathways

There are 6 Conjugation Pathways in the human body and they include:

  • Sulphation (sulfation) pathway
  • Glucoronidation pathway
  • Glutathione conjugation pathway
  • Acetylation pathway
  • Methylation (& Sulfoxidation) pathway
  • Amino Acid conjugation pathway (glycine, cysteine, glutamine, methionine, taurine, glutamic acid and aspartic acid)

These 6 conjugation pathways occur in different organs of the body.  The locations of the Phase 2 conjugation pathways are listed in Table 1.

  Table 1 Locations of Phase 2 Conjugation Systems

Conjugation System

Location in Body

Glycine conjugation

liver, kidney

Glutathione conjugation

liver, kidney

Glucuronidation

liver, kidney, intestine, lung, skin, prostate, brain

Acetylation

liver, lung, spleen, gastric mucosa, RBCs, lymphocytes

Sulphation

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.)

Amino Acid Conjugation Pathway

The Amino Acid conjugation pathway is less utilized by the body, yet is still a very important conjugation pathway. 

The conjugation of toxins with amino acids occurs in this pathway. The amino acids commonly used in this pathway include:

  • Glycine
  • Taurine
  • Glutamine

but arginine, and ornithine are also used.

image

Figure 1:  Amino acid conjugation pathways

(Source:  Wikipathways)

The Amino Acid Conjugation Pathway often includes the Acylation Pathway.  Acylation uses acyl CO-A with the amino acids glycine, glutamine and taurine. Conjugation of bile acids in the liver with glycine or taurine is essential for the efficient removal of these potentially toxic compounds.  

The main amino acid in the Amino Acid Conjugation Pathway is glycine.  Glycine is the smallest of the 20 amino acids commonly found in proteins.  Glycine is a colorless, sweet-tasting crystalline solid. It is unique among the proteinogenic amino acids in that it is achiral. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom.

Since it plays such an important role in the Amino Acid Conjugation Pathway, it is also known as the Glycination Pathway.  Salicylates and benzoate are detoxified primarily through glycination. Benzoate is present in many food substances and is widely used as a food preservative.

In humans, there is a wide variation that exist in the activity of the glycine conjugation, which is primarily due not only to genetic variations, but also to the availability of glycine in the diet.

High-protein rich foods should be consumed in the diet to ensure that the amino acid conjugation is functioning properly.  There are a number of natural substances that induce the

Amino Acid Conjugation Pathway and act as co-factors in the conjugation process.  These substances are listed in Table 2. 

Table 2 Natural Substances that Induce the Amino Acid Conjugation Pathway

 

Category

Food

Minerals

 

 

Magnesium

 

Iron

Vitamin

 

 

B Complex Vitamins (particularly

Vitamin B3 and Vitamin B6)

Amino Acids

 

 

Glycine

 

Methionine

 

Taurine

 

Cysteine

 

Glutamine


Resources:

Life Extension – Glycine (Capsules)

NOW – Glycine (Powder)


Cover Photo Source:  Perfect Health Diet


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