Wednesday, March 18, 2015Ingredients

PCA or L-pyrrolidone carboxylic acid - Part 1


Who among us has never heard of the BCP? Universally known in cosmetics, to the point where it even goes almost unnoticed in formulas, PCA has always been one of the best options for moisturizing the skin. Considered as the physiological moisturizer of reference and cited in all cosmetology textbooks because of its presence within the NMF (Natural Moisturizing Factor), PCA is now too often used as a cosmetic convenience…

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Frequently associated with sodium or potassium, which give it humectant properties while acting on intra- and extracellular water flow, PCA has always been attributed the function of"physiological transporter", without however wondering if it did not have another role, more biological, to explain its presence at high concentration at cutaneous level. Indeed, metabolite resulting from the degradation of filaggrin, protein secreted by the de
kératinocytes during epidermal differentiation and degraded at the end of the process, is not PCA rather a signal molecule activating the permanent regeneration of the skin's barrier function?

L-pyrrolidone carboxylic acid

Common name : pidolic acid

Synonyms :  2-pyrrolidone-5-carboxylic acid (chemistry)  5-oxoproline (biochemistry) or pyroglutamic acid (Merck Index) BCP (cosmetology)

Molecular weight :  129

From a chemical point of view, pyrrolidone carboxylic acid is the lactam of glutamic acid. It has an asymmetric carbon hence the existence of two active forms on polarized light (D and L) and a racemic (DL).


This point needs to be clarified here. It is indeed of the utmost importance because the three-dimensional structure of proteins, responsible for their different biological activities, requires that all the constituent amino acids belong to the same stereochemical series. All amino acids with asymmetric carbon have the L configuration. To integrate into the biological reaction chains and provide active derivatives within the body, PCA must therefore be L-form.

His story

Pyrrolidone carboxylic acid (PCA) was discovered in 1882 by Haitinger[1], who observed that when heated, glutamic acid lost a molecule of water to give a new product, pyroglutamic acid. The exact structure of the molecule was only determined in 1892 by Menozzi and Appiani[2]. However, the actual development of pidolic acid did not begin until after the Second World War. In the 1960s, Drs Monge[3], Bocher[4], Harnist[5] and Ciaceri[6], pioneers in this field, conducted studies on PCA and its salts. Since then, many patents and articles have been dedicated to this remarkable molecule worldwide, and there are now over 10,000 publications on PCA and its derivatives.

In terms of beauty, it was Gertrud Pascher[7] who first noticed the high concentration of PCA in human stratum corneum in 1956. Since then, numerous studies have been conducted on the presence of this unusual metabolite in the human body. They revealed the presence of free PCA, acid or salt, in most tissues and biological fluids and confirmed G. Pascher's hypothesis that this molecule is found mainly in the stratum corneum (97% of the PCA present in the skin is located in the stratum corneum), where it accumulates at the end of epidermal differentiation.

PCA has a carboxyl function which allows the formation of salts from minerals in particular. The low molecular weight of the PCA residue results in a higher mineral content compared to other commonly used derivatives such as gluconates or orotates. As a result, a lower amount of pidolates can be used to get the same daily intake as with gluconates and orotates.

Manufacturing process

PCA is obtained by thermal cyclisation of glutamic acid (dehydration reaction). It is obtained exclusively in the L form, thanks to a synthesis process allowing perfect control of the stereochemistry of the molecule. This is as natural a process as possible since no solvents or chemical additives are used during the various stages. Glutamic acid, on the other hand, is of vegetable origin, derived from sugar beet molasses.

The synthesis process is fully automated. The different steps are automatically linked, which guarantees perfect reproducibility of the reaction and constant product quality.
 UCIB, Solabia Group, is fully equipped to perform the glutamic acid cyclisation reaction, leading to the formation of L-PCA.

PCA, a physiological molecule

PCA is a physiological molecule present in many tissues. Although 97% of the total PCA is found in the epidermis, L-pyrrolidone carboxylic acid is found in several organs such as the brain, liver, and in biological fluids. There are also enzymes in the liver and kidney that can produce PCA.

L-PCA is a biochemical intermediate of compounds abundant in collagen: proline and hydroxyproline. - The proline ( Pro ) is a neutral non-essential amino acid. It plays an important role in protein structure by causing polypeptide chain curvature. - Hydroxyproline corresponds to the oxidized form of proline. It can also be considered as an amino acid but, unlike proline, it does not enter into protein synthesis. It is found mainly in the fibrous proteins of connective tissues, in particular elastin and collagen.

This information is particularly interesting when we know that proline and hydroxyproline together represent about 21% of the amino acids that make up collagen, the rest being mainly glycine (35%) and alanine (11%). The abundance of proline/hydroxyproline is responsible for the rigidity and stability of collagen. Collagen, the most abundant protein in the human body, constitutes the pillars of the dermis but also of the bone structure.

PCA is also a precursor of γ-aminobutyric acid (GABA), a molecule involved in adrenergic regulation and promoting relaxation. The natural function of GABA is to decrease the nerve activity of the neurons to which it attaches itself by inhibiting presynaptic transmission.

PCA, a metabolic intermediary

PCA can also be considered as a metabolic intermediate because it occurs in two physiologically important cycles, the Krebs cycle and the γ-glutamyl cycle.

- The Krebs cycle, also called citric cycle or tricarboxylic cycle, has the function of degrading the end products of the metabolism of oses, fatty acids and many amino acids, providing most of the energy that the cell needs. The Krebs cycle takes place in the mitochondria in eukaryotes. It contains eight enzymatic reactions that can be broken down into simple reactions.

- L-PCA is involved in this cycle at step 3 where α-ketoglutaric acid is formed. Indeed, this last molecule can also come from glutamic acid, itself from an L-PCA molecule.

PCA and skin: a reference moisturizer

A skin whose stratum corneum (SC) is well hydrated has a pleasant appearance. It is water that gives it its smooth touch, suppleness and elasticity. A 1% change in its water content can significantly alter its elasticity and permeability. Water is therefore the plasticizer of the stratum corneum. But this water is captured in the surrounding atmosphere or brought by a cosmetic product. This capacity of the SC is due to the presence, in the cells, of hygroscopic compounds which are themselves water-soluble. It is a complex mixture of amino acids, organic acids, urea and mineral ions called Natural Moisturizing Factor (NMF). The latter constitutes a real water reservoir within the skin. Good hydration of the skin guarantees a good metabolism, hence its importance. Among these components, L-PCA is the main catabolite of filaggrin (name derived from Filament Aggregation Protein), a protein in the granular layer of the epidermis which, during the last phase of keratinization, is broken down into a mixture of amino acids.

Composition of the NMF

Watt & colleagues define in 1989 the cellular differentiation of a keratinocyte as the sequence of events, which begins when the stem cell of the basal layer gives birth to a daughter cell having lost its capacity of unlimited division, and ends when this desquamated cell. It is during this process that L-PCA is formed from a specific protein, fillagrin. Present in significant quantities in filaggrin (27%) then in le
NMF (12%), L-PCA is therefore a moisturizing element of choice.

Filaggrin P uring their migration to the surface, keratinocytes undergo biochemical and structural modifications to result in keratin synthesis and corneocyte formation. In the final phases of differentiation, an intracornecyte fibrous matrix is formed by the interaction keratohyaline-cytokeratin. L he keratohyaline granules (insoluble protein aggregates) in the granular layer produce a highly phosphorylated protein, profilaggrin (formed from 10 to 12 units of filaggrins). E n at the end of the differentiation phase, when the granular keratinocyte is about to become a corneocyte, the profilaggrin is dephosphorylated in the stratum corneum and then cleaved to produce filaggrin units. As its name suggests, filament aggregating protein (filaggrin) aggregates cytokeratin filaments to form an intracorneocyte matrix network. C It is in the upper part of the Stratum corneum that the filaggrin is then completely hydrolyzed, producing in particular amino acids and pyroglutamic acid or PCA (pyrrolidone carboxylic acid), which is found in the composition of the NMF (Natural Moisturizing Factor), the NMF's main function being to ensure and maintain the hydration of the superficial layers of the epidermis.

nombreuses studies have attributed its moisturizing action to its pouvoir
hygroscopique[8][9]. As hydration is vital to maintain the flexibility of the stratum corneum, the action of L-PCA is paramount.
Comme there is no enzyme responsible for catabolism in the epidermis, L-PCA disappears only from the corneocytes, which explains its accumulation in the stratum corneum (which contains 10% by weight) and why there is ten times more L-PCA in the skin than in other tissues and organs, in which the anabolic/catabolism balance is respected.

In cosmetics, it is customary to use sodium PCA to further increase the humectant properties of the molecule.

Physio-activator of epidermal differentiation

However, when the keratinization process is incomplete, the level of L-PCA in the SC decreases. A healthy skin contains on average 180 mmol/g L-PCA ; below this, the skin becomes dry and rough. In addition to this unsightly and uncomfortable consequence, the L-PCA depletion is also likely to damage the barrier function exercised by the SC. Indeed, dehydrated, this structure can crack and no longer act as an effective border between our body and the surrounding world.

L-PCA, biological signal?

If the formation of L-PCA in the skin is directly related to the degradation of filaggrin and therefore more globally to the very process of epidermal differentiation, shouldn't a molecule so involved in the epidermis play a much more important role than the cosmetics industry has given it for decades?

Wouldn't the skin's L-PCA concentration be an indication of its differentiation state?

Couldn't an external contribution of L-PCA be recognized by the cutaneous cells as the sign of a significant degradation of filaggrin and induce a stimulation of the differentiation process?

So there are still many questions about the physiological interest of this exciting molecule.

In a future article, we will discuss the evidence of efficacy of this ingredient, the formulation elements, as well as a review of the state of the art, i.e. a fairly complete inventory of the different types of CACs available and their effect. We will also approach a series a little particular, esters on the basis of PCA, called Ceramidone™, kind of physiological esters because biomimetic.

HAITINGER L., Monatsch Chem, 1882, 3, 228-229.  2. MENNOZZI A., APPIANI G., Gazz Cim Ital, 1892, 22, 14; 1894, 24, 370.  3. MONGES H., Therapeutic efficacy compared to betaine chloride in double blind.  4. BOCHER G., US Patent No. 3 345 264 (03/10/1967).  5. HARNIST LF, Special Patent No. 3.593M (1964).  6. CIACERI G., Biochim Appl, 1961, 8, 173-186.
 7. PASCHER G., Die wasserlöslischen Bestandteile der peropheren Hornschicht (Hautoberfläche) Quantitative Analysen III, a- pyrrolidoncarbonsaüre, Archiv. Klein. Dermatol. 1956, 203, 234-238.
 8. CLAR E. Pyrrolidone carboxylic acid and the skin, Int. J. Cosmet. Sci, 1981, 3, 101-113 .  9. TASUMI S., Pyrrolidone carboxylic acid, Amer. Perf. Cosmet. 1972, 87, 61-63.

This contribution is possible thanks to the free collaboration of the Solabia Group .

Founded in 1972, the Solabia Group designs and manufactures molecules and active ingredients for the cosmetic, pharmaceutical and nutraceutical industries, peptones and protein hydrolysates for bio-industries and microbiological diagnostic reagents for food, cosmetic, pharmaceutical and environmental laboratories. The Solabia Group has a coherent set of complementary skills such as biotechnology, fine chemistry, plant extraction and microbiology. The cosmetics department of the Solabia group, trend decoder, has built integrated solutions based on a well differentiated and convergent scientific expertise (biotechnology, fine chemistry and extraction), by developing active ingredients and concept-formulas. Among other things, PCA Science (PCA, salts and esters) developed by the UCIB entity of the Solabia group. We would particularly like to thank Jean-François Molina who helped us to make this contribution. Jean-François is currently Sales & Marketing Director within the Solabia group. He obtained his engineering degree in biotechnology at the University of Aix-Marseille and his Masters in Product Innovation Marketing in 1989. For nearly 25 years within the Solabia group, he has successively held the position of Export Manager, Marketing Manager and now supervises the overall sales and marketing activities of the Solabia group's subsidiaries in the USA, Germany and Brazil.

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