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Pyroglutamic acid

Pyroglutamic acid, also known as 5-oxoproline or pidolic acid, is a non-proteinogenic amino acid derivative formed by the intramolecular cyclization of L-glutamic acid through lactam formation between its α-amino and γ-carboxyl groups, resulting in a five-membered pyrrolidone ring structure with the molecular formula C₅H₇NO₃ and a molecular weight of 129.11 g/mol.^[1]^[2] This compound appears as a white crystalline solid with a melting point of 160–163 °C and high water solubility of approximately 476 mg/mL at 13 °C, making it stable under physiological conditions.^[3]^[1] It occurs naturally in various biological systems, from archaebacteria to humans, and serves as an intermediate in key metabolic pathways.^[1] In human metabolism, pyroglutamic acid plays a central role in the γ-glutamyl cycle, where it is generated from glutathione degradation via the enzyme γ-glutamylcyclotransferase and is subsequently hydrolyzed back to L-glutamate by 5-oxoprolinase, facilitating amino acid transport and detoxification processes.^[1] It is endogenously produced and found in tissues such as blood (average concentration 19.5 ± 3.7 µM), urine (5–44 µmol/mmol creatinine), brain, epidermis, and placenta, with additional dietary sources including cheese.^[1] Biologically, it contributes to glutamate storage and opposes excessive glutamate activity in the brain, while pyroglutamyl peptides derived from it, such as those from neurotensin or thyrotropin-releasing hormone, modulate neurotransmission, influencing emotion, memory, learning, and appetite regulation.^[4]^[1] Elevated levels of pyroglutamic acid are associated with metabolic disorders, including 5-oxoprolinuria—an inborn error of metabolism due to deficiencies in glutathione synthetase or 5-oxoprolinase—and can lead to high anion gap metabolic acidosis, particularly in critically ill patients exposed to factors like acetaminophen overuse, manifesting in symptoms ranging from confusion to coma.^[4] Conversely, it exhibits potential neuroprotective effects, including anti-anxiety properties through GABA release and antidepressant-like actions in preclinical models by promoting neurogenesis.^[1] Beyond biology, pyroglutamic acid is utilized in peptide synthesis for enhanced stability and in industrial applications like enzymatic glutamate production.^[4]

Chemical properties

Structure and nomenclature

Pyroglutamic acid is a cyclic derivative of glutamic acid, formed through intramolecular cyclization involving the alpha-amino group and the gamma-carboxyl group, resulting in a lactam structure.^[5] This compound has the molecular formula C_5H_7NO_3 and a molecular weight of 129.11 g/mol.^[5] Its core structure consists of a five-membered pyrrolidine ring, where the nitrogen is part of a lactam (amide) linkage, and a carboxylic acid group is attached to the carbon at position 2.^[5] The systematic IUPAC name for pyroglutamic acid is (2S)-5-oxopyrrolidine-2-carboxylic acid, reflecting the oxo group at the 5-position of the pyrrolidine ring and the carboxylic acid at position 2.^[5] Common synonyms include pidolic acid and 5-oxoproline, with the latter emphasizing the proline-like ring and the keto functionality.^[5] The name "pyroglutamic acid" originates from its historical discovery in the late 1880s, when it was first produced by heating glutamic acid, leading to dehydration and cyclization—a process evoking the prefix "pyro-" derived from pyrolysis.^[6] Pyroglutamic acid exhibits chirality at the C2 position of the ring, existing as two enantiomers: (2S)-pyroglutamic acid, known as the L-form, which is the naturally predominant enantiomer in biological systems, and (2R)-pyroglutamic acid, the D-form.^[5]^[7] This stereocenter imparts optical activity, with the L-enantiomer displaying levorotatory properties (negative specific rotation).^[8] The enantiomers are non-superimposable mirror images, differing in their interactions with chiral biological environments.^[5]

Physical and chemical characteristics

Pyroglutamic acid appears as a white crystalline solid at room temperature.^[2] The L-enantiomer has a melting point of 160–163 °C, while it decomposes at higher temperatures without reaching a boiling point.^[9]^[10] It exhibits high solubility in water, approximately 100–150 g/L at 20 °C, and is soluble to a lesser extent in ethanol, methanol, and acetone, but insoluble in ether.^[11]^[12] Regarding acid-base properties, the carboxylic acid group has a pKa of 3.32 at 25 °C, allowing the molecule to exist predominantly in its zwitterionic form at neutral pH.^[12]^[13] Pyroglutamic acid demonstrates thermal stability up to its melting point and resists hydrolysis under physiological conditions, though it can decarboxylate under basic environments.^[14]^[15] Spectroscopic characterization includes infrared (IR) absorption for the carbonyl group around 1710 cm⁻¹, indicative of the carboxylic acid functionality, with the lactam carbonyl appearing near 1690 cm⁻¹.^[2] In nuclear magnetic resonance (NMR) spectroscopy, the ring protons show characteristic ¹H NMR shifts in D₂O, with the α-proton at approximately 4.0 ppm and methylene protons between 2.0–2.5 ppm.^[16]^[17]

Biosynthesis and metabolism

Biosynthetic pathways

Pyroglutamic acid, also known as 5-oxoproline, can form non-enzymatically through the cyclization of free L-glutamic acid or L-glutamine under specific conditions. The thermal cyclization of L-glutamic acid proceeds via dehydration, typically requiring heating to 160–180 °C for several hours to achieve significant conversion.^[18] This process involves the intramolecular reaction of the α-amino group with the γ-carboxyl group, resulting in the formation of the five-membered lactam ring characteristic of pyroglutamic acid. Acid-catalyzed cyclization can also occur, albeit more slowly, under harsh acidic conditions that promote dehydration.^[19] The reaction for L-glutamic acid cyclization is represented by the following equation:

\text{L-Glutamic acid} \rightarrow \text{pyroglutamic acid} + \text{H}_2\text{O}

This dehydration is thermodynamically favorable in vivo contexts, though specific ΔG values under physiological conditions are not well-documented; the equilibrium favors the cyclic form due to ring strain relief and entropy gain from water release.^[20] Enzymatic biosynthesis of pyroglutamic acid is catalyzed by γ-glutamyl cyclotransferase (GGCT, EC 2.3.2.4), which acts on γ-glutamyl dipeptides to cleave the peptide bond and form pyroglutamic acid along with the free amino acid.^[21] GGCT is widely distributed in mammalian tissues and plays a key role in amino acid turnover, utilizing substrates such as γ-glutamyl-L-alanine.^[22] Within the glutathione cycle, pyroglutamic acid arises as an intermediate during glutathione degradation. γ-Glutamyl transpeptidase (GGT) first hydrolyzes glutathione to yield γ-glutamyl-amino acid conjugates, which serve as substrates for GGCT to produce pyroglutamic acid.^[23] This pathway is prominent in erythrocytes and other tissues, contributing to the regulated turnover of glutathione and release of pyroglutamic acid for further metabolism.^[23]

Role in cellular metabolism

Pyroglutamic acid, also known as 5-oxoproline, is converted back to glutamate in cellular metabolism through the action of the enzyme 5-oxoprolinase (EC 3.5.2.2), an ATP-dependent hydrolase that requires magnesium ions (Mg²⁺) and potassium (K⁺) or ammonium (NH₄⁺) as cofactors.^[24]^[25] This enzymatic reaction regenerates glutamate for reuse in metabolic pathways, with the stoichiometry given by:

\text{5-oxoproline} + \text{ATP} + \text{H}_2\text{O} \xrightarrow{5\text{-oxoprolinase, Mg}^{2+}} \text{L-glutamate} + \text{ADP} + \text{P}_\text{i}

The process is integral to closing the loop in amino acid recycling, preventing accumulation of the cyclic form under normal conditions.^[24] Within the γ-glutamyl cycle, pyroglutamic acid serves as a key intermediate linking glutathione degradation to its resynthesis and facilitating amino acid transport across cell membranes.^[26] Formed from γ-glutamyl amino acids via γ-glutamyl cyclotransferase, it is hydrolyzed back to glutamate, which then combines with cysteine to form γ-glutamylcysteine, the precursor to glutathione.^[27] This cycle maintains intracellular pools of cysteine and glutamate, supporting antioxidant defense and transmembrane transport of amino acids, particularly in tissues like the kidney and liver.^[26] In brain metabolism, it influences energy production and lipid synthesis, potentially altering neuronal metabolic flux at millimolar concentrations.^[28] Additionally, pyroglutamic acid forms through N-terminal modification of amyloid β peptides, promoting their aggregation via cyclization of glutamine at position 3, which enhances stability and neurotoxicity in a manner distinct from full-length amyloid β.^[29] As a marker of homeostatic balance, pyroglutamic acid levels reflect glutathione turnover rates, with elevated urinary or plasma concentrations indicating perturbations in the γ-glutamyl cycle or sulfur amino acid availability. During sulfur amino acid restriction, its urinary excretion increases, signaling adjustments in cysteine-dependent glutathione synthesis and overall redox homeostasis.^[30] This positions pyroglutamic acid as a sensitive indicator of metabolic equilibrium in antioxidant and amino acid pathways.^[31]

Occurrence

In biological systems

Pyroglutamic acid, also known as 5-oxoproline, is a naturally occurring metabolite present in various biological fluids and tissues across humans and other organisms. In healthy human adults, typical plasma concentrations range from 22.6 to 47.8 μmol/L, equivalent to approximately 2.9–6.2 mg/L, as determined by hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS). Urinary levels in healthy individuals typically fall between 8.5 and 30.1 μg/mg creatinine, with fluctuations observed over time that may stabilize around 15–40 μg/mg creatinine in cycles influenced by metabolic factors. Substantial amounts are also found in brain tissue, contributing to its role as a key component in neural metabolism. Endogenous levels can vary by age, sex, and diet; for instance, menstruating females exhibit higher urinary concentrations, potentially linked to hormonal or metabolic stress, while dietary intake of amino acids such as glycine and sulfur-containing amino acids like methionine can modulate levels through impacts on glutathione synthesis. It is also obtained from dietary sources including cheese.^[32]^[31]^[1]^[31] Detection and quantification of pyroglutamic acid in biofluids rely on sensitive analytical techniques to account for its cyclic structure and low concentrations. High-performance liquid chromatography coupled with mass spectrometry (HPLC-MS), particularly HILIC-MS/MS, enables precise measurement in plasma and urine with limits of detection as low as 0.14 μmol/L, making it suitable for routine clinical and research applications. Enzymatic assays utilizing 5-oxoprolinase, which hydrolyzes pyroglutamic acid to glutamate in an ATP-dependent manner, provide a specific method for confirmation and quantification, often coupled with amino acid analysis for accuracy. Nuclear magnetic resonance (NMR) spectroscopy serves for structural confirmation in biofluids like serum, identifying characteristic proton signals while revealing artifacts such as glutamine cyclization during sample preparation.^[32]^[33]^[34]^[35] In microbial systems, pyroglutamic acid is produced through the cyclization of glutamine by bacteria and fungi, contributing to the metabolite profiles of fermented foods. Lactic acid bacteria, such as those in kimchi and fermented milk products like yogurt and kefir, generate pyroglutamic acid during fermentation, with kinetics showing increased formation after 10 days due to glutamine conversion. In Japanese fermented foods like miso, pyroglutamyl peptides derived from similar cyclization processes are abundant, arising from the activity of Aspergillus oryzae and other microbes. Fungi, including Neurospora crassa, employ glutaminyl cyclases to catalyze this cyclization, producing pyroglutamic acid as part of peptide modification pathways.^[36]^[37]^[38]^[39]^[40] Pyroglutamic acid exhibits evolutionary conservation as a ubiquitous metabolite in both prokaryotes and eukaryotes, functioning as a stress response indicator in diverse organisms. In bacteria like Escherichia coli, it accumulates under environmental stresses as part of a conserved metabolic shift toward energy preservation and amino acid recycling. This role extends to plants, where exogenous application enhances yield under water deficit by modulating stress adaptation pathways. In eukaryotes, including humans, it briefly interfaces with the glutathione cycle as an intermediate, reflecting oxidative stress dynamics without direct mechanistic overlap.^[1]^[41]^[42]^[31]

In proteins and peptides

Pyroglutamylation refers to the post-translational cyclization of N-terminal glutamine or glutamic acid residues in proteins and peptides, forming a pyroglutamic acid (pGlu) residue that blocks the amino terminus. This modification is primarily catalyzed by glutaminyl cyclase (QC), an enzyme that facilitates the intramolecular cyclization, although spontaneous non-enzymatic formation can also occur under physiological conditions, particularly for N-terminal glutamic acid. The process enhances protein stability by conferring resistance to degradation by exopeptidases, such as aminopeptidases, thereby extending the half-life of affected polypeptides.^[43]^[20]^[44] This modification is prevalent in numerous eukaryotic proteins and peptides with suitable N-terminal sequences, serving critical roles in maturation and function. For instance, in neuropeptides like thyrotropin-releasing hormone (TRH), the N-terminal pGlu is essential for biological activity, enabling proper receptor binding and signaling in the hypothalamic-pituitary axis. In the membrane protein bacteriorhodopsin from Halobacterium salinarum, the N-terminal pGlu contributes to structural integrity, particularly in maintaining the alpha-helical conformation at the protein's terminus, which is vital for its light-driven proton pump function. Similarly, in amyloid β (Aβ) peptides associated with Alzheimer's disease, N-terminal pyroglutamylation at position 3 (pE3-Aβ) promotes aggregation propensity and neurotoxicity, altering secondary structure and stability compared to unmodified forms.^[45]^[46]^[47]^[48] Functionally, N-terminal pyroglutamylation not only protects against proteolytic cleavage but also influences protein folding and conformational dynamics. In peptides and small proteins, the cyclic structure stabilizes the N-terminus, reducing flexibility and aiding in proper folding pathways, as observed in structural studies of pGlu-containing variants. For peptide hormones, this modification is indispensable for bioactivity; in TRH, pGlu ensures resistance to rapid degradation while preserving the tripeptide's hormonal efficacy. Overall, pyroglutamylation exemplifies a conserved mechanism for modulating protein longevity and function in diverse biological contexts.^[49]^[50]

Medical and pathological aspects

Associated metabolic disorders

Pyroglutamic acid, also known as 5-oxoproline, is implicated in two primary inherited metabolic disorders arising from defects in the γ-glutamyl cycle, a pathway central to glutathione metabolism. These autosomal recessive conditions disrupt the normal feedback inhibition of pyroglutamic acid production, leading to its pathological accumulation and excretion in urine, termed pyroglutamic aciduria or 5-oxoprolinuria.^[51]^[52] Generalized glutathione synthetase deficiency (GSSD) results from mutations in the GSS gene, impairing the final step of glutathione synthesis and causing unchecked γ-glutamylcysteine production, which cyclizes to pyroglutamic acid due to loss of glutathione-mediated feedback inhibition.^[53] This severe form, first described in the 1970s, manifests in infancy with chronic metabolic acidosis, hemolytic anemia, progressive neurological impairment including spastic tetraparesis, and massive urinary pyroglutamic acid excretion.^[53]^[51] In contrast, 5-oxoprolinase deficiency stems from biallelic mutations in the OPLAH gene, which encodes the enzyme that hydrolyzes pyroglutamic acid to glutamate in the γ-glutamyl cycle, resulting in isolated pyroglutamic aciduria without the acidosis seen in GSSD.^[52] This rarer disorder typically presents with mild to moderate neurological symptoms such as developmental delay, seizures, or intellectual disability, often without hemolytic features, and was first delineated in the late 20th century through biochemical and genetic analyses.^[54]^[55] Diagnosis of these disorders relies on detecting elevated urinary pyroglutamic acid levels, typically exceeding 100 mmol/mol creatinine, confirmed by gas chromatography-mass spectrometry or other metabolic profiling, alongside genetic testing for GSS or OPLAH variants.^[56]^[57] Both conditions are extremely rare, with GSSD reported in over 70 individuals worldwide and an estimated incidence below 1 in 1,000,000 births.^[58] Management focuses on supportive care, including bicarbonate for acidosis in GSSD and supplementation with N-acetylcysteine to bolster cysteine availability and mitigate glutathione depletion, though no curative therapy exists.^[59]^[60]

Toxicity and clinical conditions

Acquired pyroglutamic acidosis, also known as 5-oxoproline acidosis, is a high anion gap metabolic acidosis resulting from elevated levels of pyroglutamic acid (5-oxoproline) in the blood and urine, often triggered by external factors that disrupt the gamma-glutamyl cycle. Chronic therapeutic use of acetaminophen (paracetamol) is the most common cause, where the drug's toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) forms adducts with glutathione, depleting its stores and leading to feedback inhibition loss on gamma-glutamylcysteine synthetase. This shifts glutamate toward pyroglutamic acid formation via autocyclization, while cysteine scarcity from acetaminophen's sulfation further impairs gamma-glutamylcysteine synthesis, creating a futile ATP-depleting cycle that inhibits 5-oxoprolinase, the enzyme responsible for pyroglutamic acid breakdown to glutamate.^[61] Other precipitating factors include vigabatrin therapy, which directly inhibits 5-oxoprolinase; severe malnutrition, which exacerbates glutathione depletion; and sepsis, which increases oxidative stress and metabolic demands. Clinical manifestations typically involve acute neurological and respiratory symptoms such as confusion, altered mental status, tachypnea, nausea, and vomiting, alongside severe acidosis (pH often <7.3, bicarbonate <15 mmol/L). Urinary 5-oxoproline levels can rise up to 10-fold above normal (exceeding 200-400 µmol/mmol creatinine), serving as a diagnostic marker confirmed by mass spectrometry or gas chromatography.^[62]^[63]^[64] The condition was first linked to chronic acetaminophen use in the late 1980s, with the initial case report appearing in 1989, and has since been recognized in critically ill patients, particularly malnourished elderly women receiving multiple risk factors. In intensive care unit (ICU) settings, pyroglutamic acidosis accounts for approximately 10-20% of unexplained high anion gap metabolic acidosis cases, with mortality rates up to 20% if undiagnosed due to its rapid progression and overlap with other acidoses.^[65]^[62]^[66] Management focuses on prompt discontinuation of the offending agent, such as acetaminophen or vigabatrin, alongside supportive care including intravenous fluids to correct volume depletion and sodium bicarbonate infusion to address severe acidosis (targeting pH >7.2). N-acetylcysteine may be administered to replenish glutathione and accelerate recovery, though evidence is primarily from case series; hemodialysis is reserved for refractory cases with extreme elevations. Early recognition via urinary organic acid profiling is crucial to prevent complications like encephalopathy or multiorgan failure.^[61]^[57]^[67]

Applications and uses

In cosmetics and personal care

Pyroglutamic acid, particularly in the form of its sodium salt known as sodium pyroglutamate (Na-PCA), serves as a key humectant in cosmetics and personal care products by mimicking the skin's natural moisturizing factor (NMF). As a component of the NMF, Na-PCA attracts and retains moisture within the stratum corneum, binding up to 250 times its weight in water to enhance hydration without causing stickiness.^[68] This property makes it particularly effective for addressing dry skin and hair, where it helps maintain suppleness and elasticity by preventing dehydration.^[69] In formulations, Na-PCA is commonly incorporated into lotions, creams, shampoos, and conditioners at concentrations typically ranging from 1% to 5%, targeting dry or damaged skin and hair. These applications leverage its ability to improve skin barrier function and reduce transepidermal water loss (TEWL), with clinical studies showing up to a 25% decrease in TEWL when used in moisturizing creams.^[68] It has been featured in proprietary emollients, contributing to long-lasting hydration in over-the-counter skincare products.^[70] For hair care, it acts as a conditioning agent by reducing static and enhancing moisture retention, making it suitable for products aimed at frizzy or brittle strands.^[71] Na-PCA exhibits low toxicity, with an oral LD50 exceeding 5 g/kg in animal studies, indicating minimal risk when used topically.^[70] It is non-irritating to skin and eyes even at concentrations up to 50%, and shows no potential for phototoxicity, sensitization, or comedogenicity.^[72] The Cosmetic Ingredient Review (CIR) Expert Panel has deemed PCA and its salts, including Na-PCA, safe for use in cosmetics at current practice levels, provided they are not combined with nitrosating agents.^[73] This regulatory affirmation supports its widespread inclusion in consumer products without restrictions beyond general cosmetic guidelines.

Pharmaceutical and nutritional uses

L-pyroglutamic acid is marketed as a nootropic supplement for cognitive enhancement, with typical doses ranging from 1 to 5 g per day. It is claimed to improve memory and learning through modulation of cholinergic pathways in the brain, as it readily crosses the blood-brain barrier and influences neurotransmitter activity. However, clinical evidence supporting these effects remains limited, primarily derived from preclinical studies showing improved learning and memory in aged rats. Human studies are sparse and inconclusive, with no large-scale randomized controlled trials confirming efficacy. Magnesium pyroglutamate, also known as magnesium pidolate, is utilized in nutritional supplements to address magnesium deficiencies due to its superior bioavailability compared to inorganic forms like magnesium oxide. This organic complex enhances magnesium absorption, with studies in animal models demonstrating higher serum magnesium levels post-administration relative to other salts, potentially exceeding 20% better uptake than oxide forms in some comparisons. It is particularly applied in supplements targeting conditions such as migraines, where magnesium supplementation has shown prophylactic benefits in reducing attack frequency and severity in deficient individuals. Preclinical research has identified pyroglutamic acid's inhibitory effects on several enzymes with therapeutic potential. It acts as a potent inhibitor of phosphodiesterase-5 (PDE5), with an IC50 of 5.23 µM, suggesting applications in conditions involving cyclic nucleotide dysregulation, including potential adjunctive roles in asthma management through bronchodilatory effects. Additionally, it exhibits strong angiotensin-converting enzyme (ACE) inhibition, achieving 98.2% inhibition at 20 µg/mL, which supports its exploration for hypertension treatment by reducing angiotensin II formation. Pyroglutamic acid also inhibits urease with an IC50 of 1.8 µM, offering promise against Helicobacter pylori infections, as urease is essential for the bacterium's gastric colonization. As of 2025, ongoing clinical trials, such as phase 1 pharmacokinetic studies evaluating pyroglutamate-conjugated compounds like rongliflozin for type 2 diabetes (NCT05374343), continue to investigate its broader pharmacological applications, though dedicated trials for these enzymatic activities remain in early stages.^[74] Historically, pyroglutamic acid has been investigated for its role in ethanol detoxification, with experiments demonstrating it significantly shortens the plasma half-life of ethanol in intoxication models, potentially aiding in accelerating alcohol metabolism.

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Pyroglutamate-modified amyloid-β (Aβ pE3 ) peptides are gaining considerable attention as potential key participants in the pathology of Alzheimer disease (AD)Missing: processing | Show results with:processing
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Roles of N-terminal Pyroglutamate in Maintaining Structural Integrity ...
Our results provide a mechanistic explanation on the essential role of Pyr1 in maintaining the structural integrity, especially at the N-terminal α-helix.Missing: pyroglutamylation resistance exopeptidases
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Protein amino-terminal modifications and proteomic approaches for ...
N-terminal acetylation, pyroglutamate formation, N-degrons and proteolysis are reviewed. •. N-terminomics provide comprehensive profiling of modification at ...Missing: prevalence | Show results with:prevalence
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Entry - #266130 - GLUTATHIONE SYNTHETASE DEFICIENCY; GSSD
Pyroglutamic acid was isolated by gas chromatography and identified by mass spectrometry; it is ninhydrin-negative. The patient showed spastic tetraparesis ...
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Entry - #260005 - 5-OXOPROLINASE DEFICIENCY; OPLAHD - OMIM
5-Oxoprolinuria can be caused by genetic defects in either of 2 enzymes involved in the gamma-glutamyl cycle of glutathione metabolism: glutathione ...
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Glutathione Synthetase Deficiency, an Inborn Error of Metabolism ...
Glutathione Synthetase Deficiency, an Inborn Error of Metabolism Involving the γ-Glutamyl Cycle in Patients with 5-Oxoprolinuria (Pyroglutamic Aciduria).
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Unravelling 5-oxoprolinuria (pyroglutamic aciduria) due to bi-allelic ...
5-oxoprolinuria (pyroglutamic aciduria) is caused by a genetic defect in the γ-glutamyl cycle, affecting either glutathione synthetase or 5-oxoprolinase.
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Is 5-Oxoprolinase Deficiency More than Just a Benign Condition?
Feb 23, 2024 · The inherited condition of 5-oxoprolinuria, or pyroglutamic aciduria, is primarily caused by mutations in the genes that encode glutathione ...Abstract · Introduction · Case Presentation · Discussion
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Glutathione Synthetase Deficiency Clinical Presentation
Feb 12, 2024 · The severe phenotypic manifestation, 5-oxoprolinuria (pyroglutamicaciduria), resulting from systemic glutathione synthetase deficiency, is an ...
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Pyroglutamate acidosis 2023. A review of 100 cases - ScienceDirect
Historically, pyroglutamic acidosis was first recognised in children with one of two inherited disorders of the glutathione cycle, either glutathione synthetase ...
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Mar 1, 2015 · Frequency. Glutathione synthetase deficiency is very rare. This disorder has been described in more than 70 people worldwide.
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NAC, best known for its ability to counter acetaminophen toxicity, is a safe, well-tolerated antidote for cysteine/GSH deficiency.
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Nov 14, 2013 · In the cell, γ-glutamyl cyclotransferase (step 2) releases the transported amino acid and “cyclizes” the glutamic acid to form 5-oxoproline ( ...
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Pyroglutamic acidosis as a cause for high anion gap metabolic ...
Mar 5, 2019 · The high PGA level group (≥63 µmol/mmol creatinine) consisted of 4 (6.3%) patients of whom median PGA concentration was 72.5 (65.2–106.3) µmol/ ...
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Pyroglutamic Acidosis – An Underrecognised Entity Associated with ...
Acquired PGA, usually associated with chronic ... Additional risk factors for PGA include female sex, malnourishment, concomitant sepsis, hepatic and renal ...
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Pyroglutamic Acidosis • LITFL • CCC Acid-base
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Pyroglutamic Acidemia: An Underrecognized and Underdiagnosed ...
Jul 24, 2019 · Pyroglutamic acidemia (oxoprolinemia) is an underrecognized cause of high anion gap acidosis resulting from derangement in the ...<|separator|>
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Drug-Related Pyroglutamic Acidosis: Systematic Literature Review
Oxoprolinase, an enzyme in the lactamase family, breaks down pyroglutamic acid into glutamic acid [4]. It is speculated that β-lactamase-resistant penicillin ...
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A case report of Paracetamol related pyroglutamic acidosis
Aug 13, 2024 · Use of other drugs, such as vigabatrin, netilmicin and flucloxacillin, was also reported as an alternative cause of pyroglutamic acidosis.
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What Makes Sodium PCA a Smarter Choice for Setting Sprays?
Sodium PCA can bind up to 250 times its weight in water—a lower number than Hyaluronic Acid, but its method of action is more skin-compatible in many cases.Missing: capacity | Show results with:capacity
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https://formunova.com/our-ingredients/sodium-pca/
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Everything you need to know about Sodium PCA | FormuNova
... water retention capacity. This property enhances skin hydration, reducing transepidermal water loss by up to 25% in clinical studies, thereby improving skin ...
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Final Safety Assessment for PCA and Sodium PCA1 - Sage Journals
The oral LD50 of Sodium PCA was 10.4 g/kg for male mice. (Ajinomoto Co., Inc. 1994c). In another study, the LD50 for. 50% Sodium PCA was >2.0 g/kg for rats ...
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Sodium PCA - Cosmetics Info
Sodium PCA was nonirritating to the eye and skin at concentrations up to 50%. No evidence of phototoxicity, sensitization or comedogenicity ...
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[PDF] Safety Assessment of PCA and Its Salts as Used in Cosmetics
Aug 18, 2014 · In 1999, PCA and sodium PCA were considered safe in cosmetics. A re-review is being done to see if new data changes this conclusion.Missing: regulatory | Show results with:regulatory
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[PDF] Safety Assessment of PCA (2-Pyrrolidone-5-Carboxylic Acid) and Its ...
The panel concluded that PCA and its salts are safe in cosmetics in the present practices of use and concentration.