Pyroglutamic acid
Pyroglutamic acid (also known as PCA, 5-oxoproline, pidolic acid) is a ubiquitous but understudied natural amino acid derivative in which the free amino group of glutamic acid or glutamine cyclizes to form a lactam.<ref name=throwing/> The names of pyroglutamic acid conjugate base, anion, salts, and esters are pyroglutamate, 5-oxoprolinate, or pidolate.
It is a metabolite in the glutathione cycle that is converted to glutamate by 5-oxoprolinase. Pyroglutamate is found in many proteins including bacteriorhodopsin. N-terminal glutamic acid and glutamine residues can spontaneously cyclize to become pyroglutamate, or enzymatically converted by glutaminyl cyclases.<ref>Template:Cite journal</ref> 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.<ref>Template:Cite journal</ref>
Pyroglutamic acid exists as two distinct enantiomers:
- (2R) or D which happens to be (+) or d
- (2S) or L which happens to be (–) or l
MetabolismEdit
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.<ref name=throwing/> Pyroglutamic acid may function in glutamate storage, and acts to oppose the action of glutamate, including in the brain.<ref name=throwing/> It also acts on the brain's cholinergic system;<ref>Template:Cite journal</ref> Amyloid β containing pyroglutamic acid is increased in Alzheimer's disease; this may be part of the disease process.<ref>Template:Cite journal</ref> 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, causing high anion gap metabolic acidosis.<ref name=throwing>Template:Cite journal</ref><ref>Template:Cite journal</ref>
UsesEdit
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. It has low toxicity and is not a skin irritant, but its use in products is limited by a high price.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite book</ref>
L-pyroglutamic acid is sold online as a nootropic dietary supplement.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Magnesium pidolate, 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, and anti-urease activities.<ref>Template:Cite journal</ref>