LIVER DETOXIFICATION PATHWAYS:
The liver has two phases to detoxification. The phases are two different biochemical processes that enable the body to eliminate xenobiotics, waste metabolites, hormones and cellular debris.
PHASE I DETOXIFICATION.
This phase changes non-polar non-water soluble chemicals into polar compounds with the help of enzymes that add a polar group. At least 50 enzymes governed by 35 different genes allow phase I detoxification to take place. The major enzymes required are known as cytochrome P-450 system and the amine oxidase system. Some of the cytochrome P-450 processes occur in the lungs and kidneys which support the liver. The action of detoxification enzymes depends on the presence of various minerals. The key minerals are Zinc, Manganese, Magnesium, Sulpur, selenium and copper. They help to detoxify alcohols and aldehydes for example.
Usually enzymatic reactions in phase I decrease chemical toxicity. However, toxic or reactive chemicals can form during phase I that are more toxic than the original compound. This is known as bioactivation.
This can be detrimental to the body if phase II detoxification cannot eliminate the intermediate compound. Imbalance between phase I and II detoxification is associated with increased symptoms of nervous, immune, and endocrine system toxicity.
How do you know if you have a good functioning Phase I detoxification?
A Caffeine metabolism test. The efficiency of caffeine clearance is directly related to the efficiency of phase I detoxification.
PHASE II DETOXIFICATION
In phase II detoxification, chemical groups are added, or conjugated to the chemical. The chemical becomes water soluble and can be excreted through the kidneys or bile secretions. The conjugation pathways are:
- Acetylation. This is the chief detoxification pathway for amines and amides. Needs B5 to function.
- Glucuronidation: The major detoxification pathway for xenobiotics, melatonin hormones, steroid hormones, phenols, dyes, coal tar derivatives and certain pharmaceuticals.
- Glutathione conjugation: Reduced glutathione combines with xenobiotics to form less toxic substances. The predominant defense against free radicals (hydroxyl radical).
- Methylation: Addition of a methyl group detoxifies many synthetics and endogenous toxic compounds, including neuro-transmitters, adrenalin, noradrenalin and serotonin. B6 dependent.
- Sulphur conjugation: this includes sulfonation, which detoxifies cyanides by adding sulphur. Involved in detoxification of drugs, food additives, environmental pollutants, steroid and thyroid hormones, heavy metals. Requires more energy than other detox pathways and will not take place if energy is low.
- Acylation (amino acid conjugation): Peptide conjugation using Acyl CoA and amino acids glycine, taurine and glutamine. Important for ammonia detoxification.
How do you know if phase II detoxification is working effectively?
An acetaminophen and aspirin detox test: The test measures the recovery of the products of glutathione conjugation, sulphur conjugation, glucoronidation and glycine conjugation. Comparison to normal values allows for evaluation of the efficiency of phase II. You can compare the efficiencies of phase I and II detoxification and see if there imbalance.
The efficiency of phase I and Phase II is adversely affected by deficiencies of vitamins, minerals, amino acids and fatty acids. Inadequate protein intake specifically reduces phase I clearance, and insufficient calories decreases overall detoxification function.