Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but little studied natural amino acid derivative in which the free amino group of

glutamic acid Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) 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 synt ...

or glutamine cyclizes to form a

lactam A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''. Nomenclature Greek prefixes in alphabetical order indicate ring size: * α-Lactam (3-atom rings) * β-Lacta ...

. The names of pyroglutamic acid conjugate base, anion, salts, and esters are pyroglutamate, 5-oxoprolinate, or pidolate. Formation_of_5-oxoproline_from_N-terminal_Gln

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 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 resulting ...

. ''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 Pyroglutamate aminopeptidase is a type of enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the sub ...

can restore a free ''N''-terminus by cleaving off the pyroglutamate residue. Pyroglutamic acid exists as two distinct

enantiomers In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...

: *(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 through the action of an enzyme,

γ-glutamyl cyclotransferase In enzymology, a gamma-glutamylcyclotransferase () is an enzyme that catalysis, catalyzes the chemical reaction :(5-L-glutamyl)-L-amino acid \rightleftharpoons 5-oxoproline + L-amino acid Hence, this enzyme has one substrate (biochemistry), subst ...

. 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 Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...

;

Amyloid β Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which is ...

containing pyroglutamic acid is increased in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

; this may be part of the disease process. Increased levels of pyroglutamic acid in the blood, or

5-oxoprolinuria Glutathione synthetase deficiency (GSD) is a rare autosomal recessive metabolic disorder that prevents the production of glutathione. Glutathione helps prevent damage to cells by neutralizing harmful molecules generated during energy production. G ...

, can occur following

paracetamol overdose Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These include ...

, as well as in certain inborn errors of metabolism, causing an acidosis known as high anion gap metabolic acidosis.

Uses

The sodium salt of pyroglutamic acid—known either as sodium pyroglutamate, sodium PCA, or sodium pidolate—is used for dry skin 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 moisture ...

. 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

dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

Magnesium pidolate Magnesium pidolate, the magnesium salt of pidolic acid (also known as pyroglutamic acid), is a mineral supplement In the context of nutrition, a mineral is a chemical element required as an essential nutrient by organisms to perform functions n ...

, 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 Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme () from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to p ...

, 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 vasoconstr ...

, and anti- urease activities.

References

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