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Pyroglutamic Acid

Also known as: Pyroglutamic acid, 5-oxoproline, Pyroglutamate

Overview

Pyroglutamic acid, also known as 5-oxoproline, is a derivative of the amino acid glutamate and an intermediate in the glutathione cycle. It plays a crucial role in glutathione synthesis and breakdown. Unlike many other compounds, pyroglutamic acid is not typically used as a dietary supplement. Instead, it is primarily significant in medical diagnostics and management, particularly in cases of pyroglutamic acidosis, a metabolic disorder characterized by the accumulation of pyroglutamic acid in the body. This condition is often associated with high-anion-gap metabolic acidosis, especially in patients with certain drug exposures, such as paracetamol (acetaminophen) and β-lactamase-resistant penicillins, and underlying health conditions like kidney disease or alcohol-use disorder. Research on pyroglutamic acid is mature in the context of its role in metabolic disorders, providing high-quality evidence from systematic reviews and clinical studies.

Benefits

Pyroglutamic acid is not used as a supplement for beneficial effects. Instead, its presence at high levels is indicative of a pathological condition, namely pyroglutamic acidosis. This condition is associated with metabolic acidosis, particularly in patients using medications like paracetamol (acetaminophen) and β-lactamase-resistant penicillins. The clinical significance lies in the diagnosis and management of pyroglutamic acidosis, where elevated levels can signal severe metabolic derangement. There are no identified benefits of pyroglutamic acid supplementation, as the focus is on addressing the underlying causes of its accumulation and managing the resulting metabolic imbalance.

How it works

Pyroglutamic acid is an intermediate in the glutathione cycle. Its accumulation indicates a blockage in this cycle, often due to drug interactions or underlying health conditions. This accumulation affects the body's acid-base balance, leading to high-anion-gap metabolic acidosis. The mechanism involves the diversion of the glutathione cycle, resulting in the overproduction of pyroglutamate. This disruption can be triggered by factors such as impaired activity of 5-oxoprolinase, the enzyme responsible for converting pyroglutamic acid to glutamate, or increased production of pyroglutamic acid due to other metabolic disturbances.

Side effects

Pyroglutamic acid itself is not a supplement and does not have a safety profile in that context. However, its accumulation can be harmful and indicative of a serious metabolic condition, pyroglutamic acidosis. Common clinical features of pyroglutamic acidosis include diminished consciousness, Kussmaul breathing, nausea or vomiting, hypokalemia, and kidney function deterioration. Severe anion gap acidosis and increased risk of mortality can occur if not managed properly. The condition often arises from interactions with drugs such as paracetamol, β-lactamase-resistant penicillins, and vigabatrin. Management involves discontinuing the offending drug and may include bicarbonate, acetylcysteine, and acute kidney replacement therapy. Adults, especially women with pre-existing conditions like undernutrition, alcohol-use disorder, or kidney disease, are more susceptible.

Dosage

Not applicable as pyroglutamic acid is not used as a supplement.

FAQs

Is pyroglutamic acid a supplement?

No, pyroglutamic acid is not used as a supplement. It is a diagnostic marker for metabolic acidosis.

What does high levels of pyroglutamic acid indicate?

High levels of pyroglutamic acid indicate a potentially fatal metabolic derangement and require immediate medical attention.

How is pyroglutamic acidosis managed?

Management involves stopping the offending drug and potentially administering bicarbonate and acetylcysteine to correct the acid-base imbalance.

Can pyroglutamic acid be confused with other supplements?

Yes, but it should not be. Pyroglutamic acid is not a supplement and should not be confused with other amino acids or supplements.

Research Sources

https://d-nb.info/119229484X/34 – This source appears to be a dissertation or thesis. Without direct access, it's difficult to provide a specific summary, but dissertations often provide in-depth analysis of a particular topic, in this case likely related to drug-related pyroglutamic acidosis.
https://www.mdpi.com/2077-0383/13/19/5781 – This systematic review of drug-related pyroglutamic acidosis analyzed 131 cases and found that the condition is rare, potentially fatal, and often occurs in adults, especially women, with pre-existing conditions and on certain medications like paracetamol and β-lactamase-resistant penicillins. The review highlights the need for increased awareness and better characterization of predisposing factors.
https://pubmed.ncbi.nlm.nih.gov/38431210/ – This prospective analytical study examined 28 critically ill patients with septic shock and found that high serum and urine pyroglutamic acid levels correlated with clinical outcomes, morbidity, and mortality. The study suggests that pyroglutamic acid levels may serve as a prognostic marker in critically ill patients.
https://www.mdpi.com/2218-1989/12/10/997 – This source appears to be a scientific article published by MDPI. Without direct access, it's difficult to provide a specific summary, but it likely discusses aspects related to pyroglutamic acid's role in biological processes or disease.
https://pubmed.ncbi.nlm.nih.gov/39407841/ – This review of 100 cases emphasizes that pyroglutamic acidosis is usually iatrogenic, associated with paracetamol use, and often seen in seriously unwell patients with underlying disorders. The review also mentions anecdotal clinical evidence for the use of N-acetyl-cysteine in managing the condition.