Compendium of the most significant studies with reference to properties, intake, effects.

Santana, M., Oliveira, G., Yoshida, V., Sabha, M., & Oshima-Franco, Y. (2011). Naturally occurring ingredients as potential antiaging cosmetics. Lat Am J Pharm, 30(8), 1531-1535.

Abstract. The criteria adopted for establishing whether a determined substance has potential as a cosmetic constituent are based on the present legislation of each country. In this study, natural antiaging constituents as Fomes officinalis, rice protein and glutamic acid were pharmacologically evaluated using neuromuscular preparation. These constituents induced a neuromuscular blockade, individually and also inmixture, simulating a Botox®, but not, dimethylaminoethanol-effect. The pharmacological knowledge is beneficial since the real effect of each ingredient becomes apparent, increasing the consumer’s confidence on the antiaging cosmetic.

Jara CP, de Andrade Berti B, Mendes NF, Engel DF, Zanesco AM, Pereira de Souza GF, de Medeiros Bezerra R, de Toledo Bagatin J, Maria-Engler SS, Morari J, Velander WH, Velloso LA, Araújo EP. Glutamic acid promotes hair growth in mice. Sci Rep. 2021 Jul 29;11(1):15453. doi: 10.1038/s41598-021-94816-y. 

Abstract. Glutamic acid is the main excitatory neurotransmitter acting both in the brain and in peripheral tissues. Abnormal distribution of glutamic acid receptors occurs in skin hyperproliferative conditions such as psoriasis and skin regeneration; however, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased the expression of genes related to apoptosis in the skin, whereas glutamic acid increased cell viability and proliferation in human keratinocyte cultures. In addition, we identified the keratinocyte glutamic acid excitotoxic concentration, providing evidence for the existence of a novel skin signalling pathway mediated by a neurotransmitter that controls keratinocyte and hair follicle proliferation. Thus, glutamic acid emerges as a component of the peripheral nervous system that acts to control cell growth in the skin. These results raise the perspective of the pharmacological and nutritional use of glutamic acid to treat skin diseases. © 2021. The Author(s).

Garattini S. Glutamic acid, twenty years later. J Nutr. 2000 Apr;130(4S Suppl):901S-9S. doi: 10.1093/jn/130.4.901S. 

Abstract. This review examines progress in understanding the physiologic functions of glutamic acid in the body since the first symposium on glutamic acid physiology and biochemistry was held at the Mario Negri Institute in Milan in 1978. The topics reviewed, although not exhaustive, include the metabolism of glutamic acid, umami taste, the role of glutamic acid as a neurotransmitter, glutamate safety and the development of new drugs resulting from the knowledge of the neurodegeneration induced by high doses of glutamic acid.

Wang M, Zhang E, Yu C, Liu D, Zhao S, Xu M, Zhao X, Yue W, Nie G. Dendrobium officinale Enzyme Changing the Structure and Behaviors of Chitosan/γ-poly(glutamic acid) Hydrogel for Potential Skin Care. Polymers (Basel). 2022 May 19;14(10):2070. doi: 10.3390/polym14102070. 

Abstract. Hydrogels have been widespreadly used in various fields. But weak toughness has limited their further applications. In this study, Dendrobium officinale enzyme (DOE) was explored to improve chitosan/γ-poly(glutamic acid) (CS/γ-PGA) hydrogel in the structure and properties. The results indicated that DOE with various sizes of ingredients can make multiple noncovalent crosslinks with the skeleton network of CS/γ-PGA, significantly changing the self-assembly of CS/γ-PGA/DOE hydrogel to form regular protuberance nanostructures, which exhibits stronger toughness and better behaviors for skin care. Particularly, 4% DOE enhanced the toughness of CS/γ-PGA/DOE hydrogel, increasing it by 116%. Meanwhile, water absorption, antioxygenation, antibacterial behavior and air permeability were increased by 39%, 97%, 27% and 52%.

Ghali N, Baker D, Brady AF, Burrows N, Cervi E, Cilliers D, Frank M, Germain DP, Hulmes DJS, Jacquemont ML, Kannu P, Lefroy H, Legrand A, Pope FM, Robertson L, Vandersteen A, von Klemperer K, Warburton R, Whiteford M, van Dijk FS. Atypical COL3A1 variants (glutamic acid to lysine) cause vascular Ehlers-Danlos syndrome with a consistent phenotype of tissue fragility and skin hyperextensibility. Genet Med. 2019 Sep;21(9):2081-2091. doi: 10.1038/s41436-019-0470-9. 

Abstract. Purpose: The Ehlers-Danlos syndromes (EDS) are a group of rare inherited connective tissue disorders. Vascular EDS (vEDS) is caused by pathogenic variants in COL3A1, most frequently glycine substitutions. We describe the phenotype of the largest series of vEDS patients with glutamic acid to lysine substitutions (Glu>Lys) in COL3A1, which were all previously considered to be variants of unknown significance. Methods: Clinical and molecular data for seven families with three different Glu>Lys substitutions in COL3A1 were analyzed. Results: These Glu>Lys variants were reclassified from variants of unknown significance to either pathogenic or likely pathogenic in accordance with American College of Medical Genetics and Genomics guidelines. All individuals with these atypical variants exhibited skin hyperextensibility as seen in individuals with classical EDS and classical-like EDS and evidence of tissue fragility as seen in individuals with vEDS. Conclusion: The clinical data demonstrate the overlap between the different EDS subtypes and underline the importance of next-generation sequencing gene panel analysis. The three different Glu>Lys variants point toward a new variant type in COL3A1 causative of vEDS, which has consistent clinical features. This is important knowledge for COL3A1 variant interpretation. Further follow-up data are required to establish the severity of tissue fragility complications compared with patients with other recognized molecular causes of vEDS.

Dall'Asta V, Gazzola GC, Franchi-Gazzola R, Bussolati O, Longo N, Guidotti GG. Pathways of L-glutamic acid transport in cultured human fibroblasts. J Biol Chem. 1983 May 25;258(10):6371-9. 

Abstract, The transport of L-glutamic acid has been studied in skin-derived diploid human fibroblasts. Competition analysis in the presence and absence of Na+ and mathematical discrimination by nonlinear regression indicated that L-glutamic acid enters the cell by at least three transport systems: 1) a high affinity Na+-dependent system which has been found to be identical to the previously described system for anionic amino acids (Gazzola, G. C., Dall'Asta, V., Bussolati, O., Makowske, M., and Christensen, H. N. (1981) J. Biol. Chem. 256, 6054-6059) and which is provisionally designated as System X-AG; this route was shared by L-aspartic acid; 2) a low affinity Na+-dependent system resembling the ASC System for neutral amino acids (Franchi-Gazzola, R., Gazzola, G. C., Dall'Asta, V., and Guidotti, G. G. (1982) J. Biol. Chem. 257, 9582-9587); its reactivity toward L-glutamic acid was strongly inhibited by L-serine, but not by 2-(methyl-amino)isobutyric acid; and 3) a Na+-independent system similar to System XC- described in fetal human lung fibroblasts (Bannai, S., and Kitamura, E. (1980) J. Biol. Chem. 255, 2372-2376). The XC- system served for L-glutamic acid and L-cystine, the latter amino acid behaving as a potent inhibitor of L-glutamic acid uptake. Amino acid starvation did not change the uptake of L-glutamic acid by the two Na+-dependent systems, but enhanced the activity of System XC- by increasing its Vmax. L-Glutamic acid transport was also affected by the density of the culture. An increased cell density lowered the uptake of the amino acid by Systems ASC and XC- and promoted the uptake by System X-AG. All these variations were dependent upon changes in Vmax.

Nowowiejska J, Baran A, Hermanowicz JM, Sieklucka B, Krahel JA, Kiluk P, Pawlak D, Flisiak I. Fatty Acid-Binding Protein 7 (FABP-7), Glutamic Acid and Neurofilament Light Chain (NFL) as Potential Markers of Neurodegenerative Disorders in Psoriatic Patients-A Pilot Study. J Clin Med. 2022 Apr 26;11(9):2430. doi: 10.3390/jcm11092430.

Abstract. Psoriasis and neurodegenerative diseases (NDs) are important medical, social and economic issues. The possible relationship of psoriasis and NDs has not been established yet. This study involved 60 patients with plaque-type psoriasis. Serum concentrations of fatty acid-binding protein 7 (FABP-7), glutamic acid (GA) and neurofilament light chain (NFL), which have been hardly studied in psoriasis before, were measured by ELISA before and after 12 weeks of treatment with acitretin or methotrexate. The concentration of FABP-7 and NFL in patients before the treatment was significantly higher than in the controls (p < 0.01, p < 0.001, respectively). After the treatment their concentration decreased, although FABP-7 did so insignificantly. The concentration of GA did not differ significantly between patients and controls and before and after the treatment but we found its negative correlation with CRP (p < 0.05). The duration of psoriasis does not seem to directly affect the risk of neurodegeneration and the severity only in patients with worse skin condition. Elevated FABP-7 and NFL, which are present in the brain, may be considered as potential indicators of NDs development in psoriatics, although it surely requires further research. GA might correspond with neuroinflammation in psoriasis. Systemic antipsoriatic therapy could be studied in order to improve cognitive impairment through lowering NDs biomarkers in some cases.

Ma Q, Zhou D, DeLyria ES, Wen X, Lu W, Thapa P, Liu C, Li D, Bassett RL, Overwijk WW, Hwu P, Li C. Synthetic Poly(L-Glutamic Acid)-conjugated CpG Exhibits Antitumor Efficacy With Increased Retention in Tumor and Draining Lymph Nodes After Intratumoral Injection in a Mouse Model of Melanoma. J Immunother. 2017 Jan;40(1):11-20. doi: 10.1097/CJI.0000000000000145. 

Abstract. There is an urgent need for new clinically applicable drug-delivery methods to enhance accumulation of immune-activating drugs in tumors. We synthesized a poly(L-glutamic acid)-CpG ODN2216 conjugate (PG-CpG) and injected it intratumorally into C57BL/6 mice bearing subcutaneous B16-ovalbumin melanoma. PG-CpG elicited the same potent antitumoral activity as CpG with respect to reducing tumor growth and triggering antigen-specific CD8 T-cell responses in this well-established solid tumor model. Moreover, PG-CpG was retained significantly longer in both tumor and draining lymph nodes than was free CpG after intratumoral injection. Specifically, 48 hours after injection, 26.5%±16.9% of the injected PG-CpG dose versus 4.72%±2.61% of free CpG remained at the tumor, and 1.53%±1.22% of the injected PG-CpG versus 0.37%±0.33% of free CpG was retained in the draining inguinal lymph nodes. These findings indicate that PG is an effective synthetic polymeric carrier for delivery of immunostimulatory agents to tumors and lymph nodes.