- Assessment of liver detoxification status by measuring both Phase I and Phase II metabolites
- Assessment of chemical exposure and impairment of liver function
- The body continually attempts to eliminate chemical toxins through enzymatic processes in the liver.
- Urinary D-glucaric acid, a byproduct of phase I detoxification is a valuable indicator of chemical exposure or liver damage.
- Urinary mecapturic acids, a byproduct of phase II detoxification is a direct end product metabolites of conjugated xenobiotics* which are chemicals that enter into the body.
- Combined assessment of urinary levels of the two analytes provides valuable information about exposure to xenobiotics and liver disease, and the capacity of the liver to eliminate toxins.
Phase I – Detoxification Pathway
Converting a toxic chemical into a less harmful chemical
The phase I pathway consists of the Cytochrome P-450 mixed function oxidase enzyme pathway. These enzymes reside on the membrane of the liver cells (called hepatocytes). Human liver cells possess the genetic code for many isoenzymes (different forms) of P-450 whose synthesis can be induced upon exposure to specific chemicals. This provides a mechanism of protection from a wide variety of toxic chemicals. Excessive amounts of toxic chemicals such as pesticides can disrupt the P-450 enzyme system by causing it to become overactive through a process called ‘induction’ . This will result in high levels of damaging free radicals being produced which circulate in the body causing damage.
Measuring Phase I Detoxification of the Liver: Urinary D-Glucaric Acid
One process by which the body eliminates toxins is enzymatic detoxification in the liver. A reliable biomarker for exposure to toxic chemicals is urinary D-glucaric acid. Elevated levels of D-glucaric acid indicate induction of cytochrome p-450 enzyme of the liver (phase I which is responsible for detoxification in the body) as a result of exposure to many xenobiotics (pesticides, fungicides, petrochemicals, drugs, toluene, formaldehyde, styrenes etc.) Such exposures induce the glucuronic acid enzyme pathway and produce D-glucaric acid which is excreted in the urine and measured in this test.
Phase II – Conjugation Pathway
Removing the harmful chemical substances from the body
Phase II is the process where liver cells add another substance (ex. cysteine, glycine or a sulphur molecule) to a toxic chemical or drug, to make it less harmful. This makes the toxin or drug water-soluble, so it can then be excreted from the body through the kidney and bowel through bile or urine.
Measuring Phase II Detoxification of the Liver: Mercarpturic Acid
The urinary level of mercapturic acid indicates quantitatively the degree of activity, or capacity of phase II detoxification. Mercapturic acids are the final excretory product of detoxification and include a variety of xenobiotics that have been conjugated prior to excretion from the body. Low levels of mecapturic acids are consistent with insufficient levels of glutathione and/or cysteine. When the rate of formation of functionalized xenobiotics (phase I) exceeds the capacity of phase II detoxification, more potent toxins accumulate in the body.
* xenobiotics are chemicals which are found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual. Specifically, drugs such as antibiotics are human xenobiotics because the human body does not produce them itself nor would they be expected to be present as part of a normal diet. However, the term is usually used in the context of pollutants such as dioxins and polychlorinated biphenyls and their effect on the biota. Natural compounds can also become xenobiotics if they are taken up by another organism (e.g., uptake of natural human hormones by fish found downstream of sewage treatment plant outfalls).