L-Pyroglutamic acid

Absorption

In skin conditioning agents, it has been observed that the percutaneous absorption of 5, 10, and 20% sodium pidolic acid through human skin was 5.97, 6.78, and 5.89%, respectively .

Toxicity

High levels of pidolic acid in the blood can lead to 5-Oxoprolinuria, which can ultimately result in severe metabolic acidosis, hemolytic anaemia, or even central nervous system dysfunction .

Chemical properties

L-pyroglutamic acid has its scientific name being L-2-pyrrolidone-5-carboxylic acid. Precipitation from ethanol and petroleum ether mixture were colorless orthorhombic bipyramid crystals with the melting temperature being 162~163 °C. It is soluble in water, alcohol, acetone and acetic acid, slightly soluble in ethyl acetate, and insoluble in ether. Specific rotation-11.9 ° (c = 2, H2O). It is produced from 42% aqueous solution of glutamic acid which subjects to heating dehydration, concentration, crystallization, washing and drying to obtain L-pyroglutamic acid.

The Uses of L-Pyroglutamic acid

L-Pyroglutamic acid is an amino acid that is used in the synthesis of peptides. It has also been observed to convert when placed at the N-terminus in vivo to create IgG2 antibodies.

The Uses of L-Pyroglutamic acid

A building block for pharmaceuticals and asymmetric synthesis

The Uses of L-Pyroglutamic acid

In the resolution of racemic amines.

What are the applications of Application

L-Pyroglutamic acid is a building block for pharmaceuticals and asymmetric synthesis

Indications

There is currently no clinically approved and/or marketed medicine that relies upon pidolic acid as an active ingredient for any formal therapeutic indication.
Although pidolic acid may be sold in a variety of non-prescription, over-the-counter dietary supplement products for cognitive or memory enhancement, there are many studies that suggest that such products or such supplementation do not elicit any kind of cognitive benefit to users . In fact, the general suggestion for any such pidolic acid product is to exercise caution in their recommendation as much more research is necessary .
Pidolic acid and sodium pidolic acid are, however, used to some extent in skin and hair conditioning agents owing to their humectant characteristics .

Background

Pidolic acid is a naturally occurring but little-studied amino acid derivative that can be formed enzymatically or non-enzymatically and participates as a biological intermediate with unique pharmacodynamics in various chemical pathways . Elevations of the acid in blood levels may be associated with problems of glutamine or glutathione metabolism . Pidolic acid, in general, is found in large quantities in brain tissue and other tissues in bound form, like skin .
There are currently little to no medicines available that are clinically approved or marketed for employing pidolic acid as an active ingredient for any particular formal indication. Although pidolic acid is included in some over-the-counter, non-prescription dietary supplements for the proposed purpose of facilitating cognitive or memory enhancement, most available research suggest exercising caution in their recommendation as much more research is necessary .

Definition

ChEBI: An optically active form of 5-oxoproline having L-configuration.

Flammability and Explosibility

Not classified

Pharmacokinetics

Pidolic acid is a naturally occurring but little-studied amino acid derivative that can be formed enzymatically or non-enzymatically and participates as a biological intermediate in various chemical pathways . Elevations of the acid in blood levels may be associated with problems of glutamine or glutathione metabolism . Pidolic acid, in general, is found in large quantities in brain tissue and other tissues in bound form, like skin .
Moreover, pidolic acid in high enough levels can act as an acidogen capable of inducing acidosis and a metabotoxin that can result in adverse health effects . Chronically elevated levels of pidolic acid are associated with at least five inborn errors of metabolism including 5-oxoprolinuria (where 5-oxoproline is otherwise known as pidolic acid), 5-oxoprolinase deficiency, glutathione synthetase deficiency, hawkinsinuria, and propionic acidemia . In particular, abnormally high levels of organic acids like pidolic acid in the blood, urine, brain, and/or other tissues results in general metabolic acidosis . Such acidosis generally occurs when arterial pH falls below 7.35 . In infants, the initial symptoms of acidosis consist of poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy . Eventually, acidosis and the symptoms of acidosis can lead to heart, liver, and kidney abnormalities, seizures, coma, and possibly even death . Many children who are afflicted with organic acidemias experience intellectual disability or delayed development. In adults, acidosis or acidemia is characterized by headaches, confusion, feeling tired, tremors, sleepiness, and seizures .
High levels of pidolic acid in the blood have also been demonstrated following acetaminophen overdose, causing an increased level of acidity called a high anion gap metabolic acidosis .

Metabolism

In living cells, various metabolic pathways involving pidolic acid exist: (a) glutamyl/glutaminyl (amino acid) n is converted to pyroglutamyl- (amino acid) n by glutaminyl cyclase, pyroglutamyl- (amino acid) n is then metabolised to pyroglutamic acid (pidolic acid) by pyroglutamyl peptidase; (b) via the gamma-Glutamyl cycle, gamma-Glutamyl transpeptidase generates gamma-Glutamyl amino acid which is metabolised to pyroglutamic acid via gamma-Glutamyl cyclotransferase; (c) glutamate via gamma-Glutamylcysteine synthetase or Glutamine synthetase or Glutamate 5-kinase metabolism generates gamma-Glutamyl phosphate which itself can be converted to pyroglutamic acid; and (d) glutamate or glutamine can be non-enzymatically converted to pyroglutamic acid . Finally, pyroglutamic acid (or pidolic acid) itself is metabolized to glutamate via the 5-Oxoprolinase enzyme .

Purification Methods

Crystallise S-pyroglutamic acid by dissolving it in boiling EtOH (20g in 100mL), cooling and after a few minutes additing pet ether (b 40-60o, 120mL), then after 5 minutes adding a further 120mL, and coThis has m 155.5-157.5o and [] D -11.4o (c 4.4, H2O) [Hardy Synthesis 290 1978, Pellegata et al. Synthesis 614 1978]. The NH4 salt has m 184-186o (from EtOH). [Beilstein 22/6 V 7.]