D-Glucaric Acid (Phase I)

check icon Optimal Result: 40 - 400 nM/mg.

The human body attempts to eliminate xenobiotics (foreign organic chemicals) through a concerted effort of enzymatic “functionalization” (phase I) and conjugation (phase II).

Functionalization involves chemical modification of the xenobiotic by the cytochrome P-450 or the “mixed function oxidase” enzyme systems. Once functionalized, the altered xenobiotic can then be conjugated and excreted.

Urinary D-glucaric acid, a hepatic byproduct of enzymatic response to chemical toxins (phase I), is a reliable indicator of exposure to xenobiotics.

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 enzymes (phase I) as a result of exposure to many xenobiotics (= substances that are foreign to the body), including pesticides, fungicides, petrochemicals, drugs, toluene, formaldehyde, styrenes and more. Such exposures induce the glucuronic acid enzymatic pathway and production of D-glucaric acid, thus urinary D-glucaric acid is an indirect byproduct of chemical exposure and phase I detoxification reactions.

What does it mean if your D-Glucaric Acid (Phase I) result is too high?

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 enzymes (phase I) as a result of exposure to many xenobiotics (= substances that are foreign to the body), including pesticides, fungicides, petrochemicals, drugs, toluene, formaldehyde, styrenes and more. Such exposures induce the glucuronic acid enzymatic pathway and production of D-glucaric acid, thus urinary D-glucaric acid is an indirect byproduct of chemical exposure and phase I detoxification reactions.

Elevated results are consistent with clinically significant exposure to xenobiotics and enhanced phase I detoxification. Check mercapturic acid levels to evaluate the status of phase II detoxification that is required for the final elimination of the toxin(s). Severe xenobiotic exposure with markedly elevated D-glucaric acid levels (>3X normal) may be associated with impaired chemical functionalization or limited phase II activity. Elevated urinary excretion of D-glucaric acid is an indication of induction of cytochrome P-450 enzymes (phase I) in the liver that may be the result of exposure to any of over 200 different xenobiotics (e.g. pesticides, herbicides, fungicides, petrochemicals, drugs, alcohol, toluene, xylene, formaldehyde, styrenes, ibuprofen etc.). Occupational and environmental exposure to toxic compounds causes induction of the glucuronic acid enzyme pathway and production of D-glucaric acid, thus D-glucaric acid excretion is considered an indirect by-product of detoxification reactions. Elevated levels of urinary D-glucaric acid have been correlated with viral hepatitis and jaundice, and have also been found in patients receiving antirheumatic drugs, independent of disease activity. With elevated levels of D-glucaric acid, there is an increased need for antioxidant protection because toxins that are processed through phase I generate free radicals that require quenching or neutralization. It is important to consider that phase I detoxification tends to become less active with aging.

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What does it mean if your D-Glucaric Acid (Phase I) result is too low?

Occupational and environmental exposure to toxic compounds invokes increased production of D-glucaric acid, thus urinary D-glucaric acid is considered an indirect by-product of phase I detoxification reactions. If the D-glucaric acid levels are low it may reflect:

(1) dysfunction of the liver’s phase I enzymatic response to foreign chemicals (possibly due to lead or other heavy metal exposure),

(2) an environment unusually free of xenobiotics, or

(3) severe malnutrition as in Kwashiorkor (extremely rare).

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