Pyroglutamate (or 5-Oxoproline) is an intermediate in the glutathione metabolism and a marker of glutathione deficiency.
Pyroglutamate is a step in the production/recycling of glutathione. Glutathione is one of the most potent anti-oxidants in the human body. It is especially important in getting rid of toxins, including the harmful metabolites of estrogen detoxification 4-OH-E1 and 4-OH-E2.
In healthy individuals, a very modest amount of Pyroglutamate is spilled in the urine.
DECREASED urinary pyroglutamate levels if:
→ Arsenic exposure
→ Medical conditions
Autism spectrum disorder
→ Protein-calorie malnutrition or protein malabsorption
LOW LEVELS of pyroglutamate may occur if there are nutritional enzyme inhibitions or inherited low-activity enzyme variants present in the synthesis pathway, or if there are low levels of its precursor glutathione available. Pyroglutamate is a breakdown product of glutathione; it can be used on a different biochemical pathway to synthesize glutamate, one of the building blocks for glutathione. The recycling of glutathione increases with increased oxidative stress. Glutathione levels may also be affected by low dietary protein, liver disorders, inflammation, infections, stress hormones and high blood sugar. Arsenic exposure may decrease pyroglutamate and increase hippurate levels. Pyroglutamate and lactate levels may be lower in some individuals with Autism Spectrum Disorder (ASD).
→ If indicated, consider supporting glutathione synthesis with vitamins B6, glycine and N-acetylcysteine. If there is no response to these nutrients, consider the use of oral liposomal glutathione instead.
→ High levels of methylmalonate and quinolinate, with low levels of cis-aconitate and isocitrate, may also indicate oxidative stress. Consider antioxidant supports.
→ Arsenic may be found in well water, in factory-farmed poultry, alcoholic beverages and as a pesticide contaminant in conventionally-farmed fruits and vegetables. Arsenic exposure can increase alpha-ketoglutarate and pyruvate, while citrate, succinate, and pyroglutamate levels decrease.
Elevated urinary pyroglutamate (= 5-Oxoproline) levels when:
→ Inborn errors of metabolism
→ Medical conditions
Sickle cell anemia
High-risk HPV infection may increase
→ Oxidative stress
→ Pyroglutamic acid supplements
→ Toxic metals (except arsenic)
HIGH LEVELS of pyroglutamate may occur if there are inherited low-activity enzyme variations on its breakdown pathway or if there are higher levels of its downstream products glutamate/glutamine. High levels of downstream products can inhibit the further breakdown
of pyroglutamate. Pyroglutamate is an intermediary in the glutathione recycling pathway that increases as the rate of glutathione recycling and oxidative stress increases. Pyroglutamate levels can increase, and hippurate levels decrease, with exposure to toxic metals (other than arsenic). Pyroglutamate may be used as a supplement to enhance cognitive performance and reduce anxiety. High levels of Firmicutes bacteria (Clostridia, Lactobacillus, etc.) in the gut microbiome may contribute to pyroglutamate levels.
→ Support glutathione synthesis, recycling, and antioxidant functions
→ If indicated, consider an evaluation of the gastrointestinal microbiome.
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