Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but understudied natural

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

derivative in which the free amino group of

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

glutamine Glutamine (symbol Gln or Q) is an α-amino acid that is used in the biosynthesis of proteins. Its side chain is similar to that of glutamic acid, except the carboxylic acid group is replaced by an amide. It is classified as a charge-neutral ...

cyclizes to form a

lactam A lactam is a Cyclic compound, cyclic amide, formally derived from an amino alkanoic acid through cyclization reactions. The term is a portmanteau of the words ''lactone'' + ''amide''. Nomenclature Greek_alphabet#Letters, Greek prefixes in alpha ...

. The names of pyroglutamic acid

conjugate base A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid gives a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as it loses a hydrogen ion in the reve ...

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conven ...

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

s, and

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

s are pyroglutamate, 5-oxoprolinate, or pidolate. Formation_of_5-oxoproline_from_N-terminal_Gln

It is a metabolite in the glutathione cycle that is converted to glutamate by 5-oxoprolinase. Pyroglutamate is found in many proteins including

bacteriorhodopsin Bacteriorhodopsin (Bop) is a protein used by Archaea, most notably by Haloarchaea, a class of the Euryarchaeota. It acts as a proton pump; that is, it captures light energy and uses it to move protons across the membrane out of the cell. The res ...

. ''N''-terminal glutamic acid and glutamine residues can spontaneously cyclize to become pyroglutamate, or enzymatically converted by glutaminyl cyclases. This is one of several forms of blocked ''N''-termini which present a problem for ''N''-terminal sequencing using Edman chemistry, which requires a free primary amino group not present in pyroglutamic acid. The enzyme pyroglutamate aminopeptidase can restore a free ''N''-terminus by cleaving off the pyroglutamate residue. Pyroglutamic acid exists as two distinct

enantiomers In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

: *(2''R'') or D which happens to be (+) or ''d'' *(2''S'') or L which happens to be (–) or ''l''

Metabolism

As first discovered in 1882, pyroglutamic acid can be formed by heating glutamic acid at 180 °C, which results in the loss of a molecule of water. In living cells, it is derived from

glutathione Glutathione (GSH, ) is an organic compound with the chemical formula . It is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources ...

through the action of an enzyme, γ-glutamyl cyclotransferase. Pyroglutamic acid may function in glutamate storage, and acts to oppose the action of glutamate, including in the brain. It also acts on the brain's cholinergic system; Amyloid β containing pyroglutamic acid is increased in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

; this may be part of the disease process. Increased levels of pyroglutamic acid in the blood, leading to excess in the urine ( 5-oxoprolinuria), can occur following paracetamol overdose, as well as in certain

inborn errors of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substr ...

, causing

high anion gap metabolic acidosis High anion gap metabolic acidosis is a form of metabolic acidosis characterized by a high anion gap (a medical value based on the concentrations of ions in a patient's serum). Metabolic acidosis occurs when the body produces too much acid, or when ...

Uses

The

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

of pyroglutamic acid—known either as sodium pyroglutamate, sodium PCA, or sodium pidolate—is used for

dry skin Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin. The term derives . In most cases, dry skin can safely be treated with moisturizers (also called emollients). Xeroderma occurs ...

and hair products, as it is a

humectant A humectant is a hygroscopic (water-absorbing) substance used to keep things moist. They are used in many products, including food, cosmetics, medicines and pesticides. When used as a food additive, a humectant has the effect of keeping moistu ...

. It has low toxicity and is not a skin irritant, but its use in products is limited by a high price. L-pyroglutamic acid is sold online as a

nootropic Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...

dietary supplement A dietary supplement is a manufactured product intended to supplement a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...

Magnesium pidolate Magnesium pidolate, the magnesium salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural cr ...

, the magnesium salt of pyroglutamic acid, is found in some mineral supplements. In a preclinical study, additional pharmacological properties of pyroglutamic acid were revealed such as anti- phosphodiesterase type 5, anti-

angiotensin-converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasocon ...

, and anti-

urease Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous Bacteria, Archaea, fungi, algae, plants, and some invertebrates. Ureases are nickel-containing metalloenzymes of high ...

activities.

References

{{Protein primary structure Pyrrolidones Alpha-Amino acids Glutamates Non-proteinogenic amino acids Cyclic amino acids Secondary amino acids