Glutamic Acids: Properties, Function, Benefits, and Sources

What is glutamic acid?

Glutamic acid (Glutamate) is a nonessential amino acid mostly utilized and synthesized as its sodium salt, monosodium glutamate (MSG). Glutamic acid is present in both animal and plant proteins. of 1908, glutamic acid was recognized as the principal constituent of a seaweed extract, commonly utilized in Asian cuisine, and was patented and commercialized as a flavor enhancer in its sodium salt form—MSG—by Ajinomoto Corp. in Japan. Glutamic acid was originally synthesized, but fermentation methods were established in 1957 and are now the predominant production technique. The fermentation medium comprises strains of corynebacteria or brevibacteria that produce glutamic acid, together with carbon sources (glucose and molasses), inorganic salts, and biotin. Analogous to lysine production, ultrafiltration (UF) can be employed post-fermentation for the preliminary separation of microorganisms and glutamic acid, subsequently concentrating the glutamic acid in the UF permeate by reverse osmosis (RO) prior to evaporation and crystallization. Alternatively, ion-exchange may be employed for the recovery of glutamic acid, while reverse osmosis might serve as the preliminary concentration step prior to additional processing.

Glutamic acid structure

Glutamic acid's structure comprises the typical amino acid backbone (an amino group, a carboxyl group, and a core alpha carbon), along with an extra carboxyl group in its side chain. Glutamic acid is chiral, with two enantiomers: d(−) and l(+), which are mirror images of each other. The L form is more prevalent in nature, whereas the D form appears in specific situations, including bacterial capsules and cell walls (where it is synthesized from the L form by the enzyme glutamate racemase) and the livers of mammals.

L-glutamate and D-glutamate. (Chang C H., et al., 2020)

Glutamic acid pKa

The reduction in pKa is due to the inductive withdrawal of electron density by the "group" attached to the carboxyl group. Because of this mechanism, carbalic acids gain acidity. When compared to glutamic acid, aspartic acid has an electron-withdrawing group—the ammonium group—that is located closer to the acidic site. A logarithmic scale is employed for pKa. The 0.36 pKa unit differential between glutamic acid and aspartic acid makes glutamic acid approximately twice as potent. Aspartic acid has a lower pKa value for its COOH side chain (3.92 vs. 4.32), as could be expected. Despite their structural similarities, asparagine and aspartic acid have differing pKa values for their -ammonium and -carboxyl groups due to the higher inductive action of carboxylate groups on ionization sites compared to amide groups. Compared to glutamine, the action of glutamic acid is smaller since its groups are located further from the ionization sites. As more links are added to the chain that connects the groups to the reaction site, the discrepancy in their impacts becomes less pronounced, if not eliminated altogether.

The pka of Aspartic acid and glutamic acid. (Ouellette R J, et al., 2015)

The pka of amino acids. (Ouellette R J, et al., 2015)

Glutamic acid charge

Upon dissolution of glutamic acid in water, the amino group (−NH₂) may acquire a proton (H+), while the carboxyl groups may relinquish protons, contingent upon the acidity of the environment. In adequately acidic conditions, both carboxyl groups are protonated, resulting in the molecule becoming a cation with a singular positive charge, HOOC−CH(NH₃⁺)−(CH₂)₂−COOH. At pH values ranging from approximately 2.5 to 4.1, the carboxylic acid next to the amine often undergoes deprotonation, resulting in the formation of the neutral zwitterion −OOC−CH(NH₃⁺)−CH₂)₂−COOH. This represents the compound's structure in the crystalline solid state. The alteration in protonation state is incremental; the two forms exist in equal amounts at pH 2.10.

At elevated pH levels, the additional carboxylic acid group dissociates its proton, resulting in the predominance of the glutamate anion −OOC−CH(NH₃⁺)−CH₂)₂−COO⁻, which has a net negative charge. The alteration in protonation state transpires at pH 4.07. This form, characterized by both carboxylates devoid of protons, predominates within the physiological pH range of 7.35 to 7.45. At elevated pH, the amino group relinquishes the additional proton, resulting in the dominant species being the doubly-negative anion −OOC−CH(NH₂)−CH₂)₂−COO⁻. The alteration in protonation state transpires at pH 9.47.

Glutamic acid solubility

Glutamic acid exhibits high solubility in water, which is notably increased at physiological pH due to its zwitterionic state. l-Glutamic acid is a characteristic polymorphic chemical. The disintegration rate of the metastable form exceeds the nucleation and growth rate of the stable form. The solubility of β-form l-glutamic acid in various binary combinations was determined using a gravimetric technique. The results demonstrate that the solubility of the -form diminishes with rising antisolvent concentration, and for a constant solvent composition, solubility declines as the polarity of the antisolvents increases. The solubility of β-form l-glutamic acid in pure water and ethanol + water at temperatures ranging from 293 K to 328 K was also assessed. The results indicate that the solubility of both forms increases with growing temperature. The dissolving enthalpy and entropy of both forms were determined by connecting solubility and temperature through the van't Hoff equation. The β-form of l-glutamic acid demonstrates reduced solubility and increased dissolution enthalpy compared to the α-form. The solubility ratios of β-form l-glutamic acid in several solvent systems indicate that all ratios are below 2, with relative standard deviations under 5%.

Mole fraction solubility of α-form and β-form glutamic acid in water. (Mo Y., et al., 2011)

Dissolution enthalpy and entropy of α-and β-form of l-glutamic acid. (Mo Y., et al., 2011)

Aspartic acid vs glutamic acid

The extra carboxyl group on amino acids like aspartic acid and glutamic acid allows them to release a proton and take on a negative charge in bodily fluids when the pH is low. Aspartate and glutamate are two examples of amino acids that are commonly referred to by their ionized forms. Because of their polar and charged functional groups, aspartic acid and glutamic acid are both hydrophilic. Because of their ionic nature and ability to form hydrogen bonds, they can have positive interactions with molecules of water. Acidic amino acids glutamic acid and aspartic acid are structurally and functionally similar; however, glutamic acid's side chain is longer and its carboxyl group on the side chain has a little higher pKa. Glutamic acid is an essential neurotransmitter in the nervous system, and both amino acids—which are polar and hydrophilic—play critical roles in protein function and cell signaling.

Acidic Amino Acids. (Blanco A., et al., 2017)

Glutamic acid amino acids at Creative Peptides

Glutamic acid benefits

Glutamate and glutamine are both essential in the metabolism of ammonia. They control the body's nitrogen equilibrium by playing an essential role in ammonia disposal. The transamination reaction is essential for the production of glutamate because it allows amino acids to transfer their amino group to a-ketoglutarate. Glutamate is involved in the process of oxidative deamination in the liver or the creation of non-essential amino acids; it also works as an amino group acceptor from other amino acids.

Glutamate and glutamine are crucial for the growth, repair, and regeneration of proteins. The kidney, lymphocytes, and monocytes use it as a substrate for gluconeogenesis and as a precursor for purine/pyrimidine. Skeletal muscle injuries are associated with decreased glutamine levels, which may suggest a function for glutamine in protein synthesis in injured muscles. Based on this, patients with injuries or infections have been supplemented with stable glutamine derivatives in total parenteral nutrition (TPN). Reasons for its improvement include its protective role against total peripheral nitrogen-related hepatic dysfunction, its capacity to modify negative nitrogen balance, and its effects on hepatic protein production and breakdown. It appears that glutamine and glutamate transporters in the heart and skeletal muscles help regulate protein metabolism throughout the body by maintaining a steady-state concentration of amino acids in the intracellular space, likely through osmotic signaling pathways.

The metabolism of glutamine and glutamate in the placenta and during pregnancy is demonstrated to be very significant. Milk is thought to play a significant role in postnatal development due to its high glutamate content in its free form. In addition, there is evidence that supplementing with glutamine and glutamate can have a positive impact on low birth weight newborns, particularly those in critical illness, by reducing the risk of nosocomial infections.

Muscle, hair, and skin proteins contain glutamate in its bound form, which is attached to other amino acids. Protein development, regeneration, and repair are all processes in which glutamate plays a crucial role in the human body. The bound form of glutamate makes up the majority of an adult's 1.5-2 kilogram body content. It is well-established that glutamate is the primary and traditional excitatory neurotransmitter in the CNS. Pharmacological characterization of many subtypes of glutamate receptors has been completed. They may function as metabotropic receptors in addition to being ligand gated. The exact number of subunits and their topographies have not been determined yet. Glutamate is involved in both normal and abnormal synaptic plasticity, which are long-term changes in the brain. It mediates quick excitatory synaptic transmission through AMPA and kainate receptors and gradual excitatory response through NMDA receptors.

Glutamic acid function and application

(1) Glutamic acid enhacnes hair growth in mice

Exogenous glutamic acid stimulates hair growth and keratinocyte proliferation by ex vivo, in vivo, and in silico methodologies. The topical administration of glutamic acid reduced the expression of apoptosis-related genes in the skin, while simultaneously enhancing cell survival and proliferation in human keratinocyte cultures. Moreover, the excitotoxic concentration of glutamic acid in keratinocytes indicates the presence of a unique skin signaling pathway regulated by a neurotransmitter that regulates the proliferation of keratinocytes and hair follicles. Consequently, glutamic acid functions as a constituent of the peripheral nervous system that regulates cellular proliferation in the skin. These findings suggest the potential pharmacological and nutritional application of glutamic acid in the treatment of dermatological conditions.

Glutamic acid stimulates hair growth and increased BrdU + cells. (Jara C P., et al., 2021)

(2) Reduce blood pressure

Participants in this cross-sectional epidemiological study ranged in age from 40 to 59 and came from 17 different randomly selected populations in the US, UK, China, and Japan. Eight readings of blood pressure (BP) were taken at four separate visits; information about the subjects' diets (83 nutrients and 18 amino acids) was culled from two timed 24-hour urine samples and four standardized, multipass 24-hour meal recalls. Blood pressure was found to be inversely associated to dietary glutamic acid, which is a percentage of total protein intake. The estimated average blood pressure differences associated with a glutamic acid intake that was higher by 4.72% of total dietary protein (2 SD) ranged from -1.5 to -3.0 mm Hg systolic and -1.0 to -1.6 mm Hg diastolic, with z scores ranging from -2.15 to -5.11. These differences were found across five different multivariate regression models, model 1 of which accounted for age, gender, and sample, and model 5, which included 16 potential nonnutrient and nutrient confounders. The findings for the glutamic acid-BP association were consistent with all of the other amino acids included in the model. For instance, when 15 factors were controlled for, including proline, the systolic/diastolic pressure differences were -2.7/-2.0 mm Hg (z scores -2.51, -2.82). There were minor changes in blood pressure and z-scores related with increasing consumption of each amino acid by 2 standard deviations in these 2-amino acid models. The adverse relationship between vegetable protein and blood pressure may be attributable, in part, to the independent BP-lowering effects of dietary glutamic acid.

Mean SBPand DBP by country-specific quartiles of glutamic acid intake. (Macronutrients M., 2009)

(3) Enhance tolerance to hypoxia and cold

Research on animals has shown that supplementing with glutamic acid lowers the heart-to-body weight ratio, which is elevated in hypoxia, and that animals treated with glutamic acid have a greater resistance to rectal temperature drops after cold stress than control animals. Based on these results, it seems that glutamate, when taken at the right dosages, might improve cold and hypoxia tolerance.

(4) Reshape the plant microbiota

Concurrent with strawberry plant aging was the decline in population density and loss of variety of the core bacterium Streptomyces globisporus SP6C4. In this study, we demonstrate that glutamic acid changes the composition of plant microbes and increases numbers of Streptomyces, a key component of strawberry anthosphere function. Glutamic acid treatment also enhanced Streptomyces, Bacillaceae, and Burkholderiaceae populations in the tomato rhizosphere. Also, there was a marked decrease in botrytis and fusarium-related illnesses in both settings. Glutamic acid has an immediate and profound effect on the microbiome's make-up. We know a lot about the make-up of microbial communities associated with plants, but not nearly as much about the mechanisms that regulate their complexity and composition. It is possible to manipulate the microbiota composition and, by extension, the intrinsic glutamic acid content in planta through the administration of an exogenous biostimulant.

Changes in microbial community structure coincident with glutamic acid treatment. (Kim D R., et al., 2021)

(5) As a food additive

Glutamic acid compound (Monosodium glutamate) is a prevalent naturally occurring amino acid commonly utilized as a taste enhancer. It generated a distinctive flavor that is not offered by the other fundamental tastes (saltiness, sourness, sweetness, and bitterness), known as the fifth taste (umami). Glutamate works in the body by acting as an energy source for specific tissues and as a substrate for glutathione synthesis. Glutamate may augment food consumption in elderly adults, and dietary free glutamate stimulated a visceral response from the stomach, colon, and portal vein. Minimal amounts of glutamate, when combined with a diminished quantity of table salt in food preparation, provide a significant reduction in salt usage during and after cooking. Due to glutamate being one of the most extensively researched food components and deemed safe, the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization and World Health Organization classified it in the safest category for food additives.

(6) Activate ROS scavenging system

The impact of exogenous glutamate administration on the qualitative characteristics, γ-aminobutyric acid (GABA) shunt, phenylpropanoid pathway, and antioxidant capability of fresh-cut carrots was examined. The results indicated that glutamate treatment mitigated the increases in lightness and whiteness values, reduced the degradation of total carotenoids, and preserved superior flavor and taste in fresh-cut carrots. Furthermore, glutamate administration swiftly enhanced the activities of glutamate decarboxylase and GABA transaminase, hence increasing GABA levels. It markedly increased the activities of phenylalanine ammonia-lyase, cinnamate-4-hydroxylase, and 4-coumarate coenzyme A ligase, while also facilitating the buildup of total phenolics and key individual phenolic compounds, such as chlorogenic and caffeic acid. Furthermore, the application of glutamate stimulated the activity of reactive oxygen species-related enzymes, including peroxidase, superoxide dismutase, ascorbate peroxidase, and catalase, hence enhancing the antioxidant capacity in fresh-cut carrots. The results indicated that exogenous glutamate treatment preserved superior nutritional quality and mitigated color degradation by promoting the accumulation of GABA and phenolics, while improving the antioxidant activity in fresh-cut carrots.

Glutamate maintains quality and antioxidant capacity of fresh-cut carrots. (Zhang J., et al., 2024)

(7) Regulate prostate function

Substantial levels of glutamic acid in the prostate gland are said to be involved in its regular function. A study involving 45 males administered glutamic acid in doses of 780 mg for 2 weeks, followed by 390 mg for the subsequent 2.5 months, in conjunction with equal quantities of alanine and glycine, shown considerable reduction in symptoms related to prostatic hyperplasia. Consequently, GA is asserted to be advantageous for patients with prostatic hyperplasia.

FAQ

Is glutamic acid acidic or basic?

Glutamic acid is categorized as an acidic amino acid owing to the existence of two carboxyl groups in its structure. The side chain carboxyl group of glutamic acid possesses a pKa of roughly 4.25, indicating that it deprotonates at this pH, hence enhancing its acidic nature. The alpha carboxyl group (on the backbone) possesses a low pKa (about 2.19), hence enhancing the acidic characteristics of glutamic acid.

Is glutamic acid polar or nonpolar?

Glutamic acid's backbone and side chains both include carboxyl groups (-COOH), which are able to create hydrogen bonds with water molecules, making them very polar. A polar amino group (-NH₂) can also generate hydrogen bonds, particularly at physiological pH when protonated to - NH₃⁺. Glutamic acid is a zwitterion at physiological pH (~7.4), and it has a positive charge on the amino group (-NH₃⁺) and a negative charge on the carboxyl groups (-COO^-). Its polarity and water solubility are further improved by this charge separation. Thus, glutamic acid is an amino acid with polarity.

Is glutamic acid hydrophobic or hydrophilic?

Because it contains polar and charged groups that can interact with water molecules, glutamic acid is hydrophilic and very soluble in water. Due to the absence of nonpolar, water-repellent groups, it cannot be considered hydrophobic.

References

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2. Ouellette R J., et al., 27 - Amino Acids, Peptides, and Proteins [M]//OUELLETTE R J, RAWN J D. Organic Chemistry Study Guide. Boston; Elsevier. 2015: 569-86.
3. Mo Y., et al., Solubility of α-form and β-form of l-glutamic acid in different aqueous solvent mixtures, Fluid Phase Equilibria, 2011, 300(1-2): 105-109.
4. Blanco A., et al., Medical biochemistry, Academic Press, 2017.
5. Kulkarni C., et al., L-Glutamic acid and glutamine: Exciting molecules of clinical interest, Indian journal of pharmacology, 2005, 37(3): 148-154.
6. Jara C P., et al., Glutamic acid promotes hair growth in mice, Scientific reports, 2021, 11(1): 15453.
7. Macronutrients M. Glutamic Acid, the Main Dietary Amino Acid, and Blood Pressure, 2009.
8. Kim D R., et al., Glutamic acid reshapes the plant microbiota to protect plants against pathogens, Microbiome, 2021, 9: 1-18.
9. Jinap S., et al., Glutamate. Its applications in food and contribution to health, Appetite, 2010, 55(1): 1-10.
10. Zhang J., et al., Glutamate application maintains quality and antioxidant capacity of fresh-cut carrots by modulating GABA shunt, phenylpropanoid and ROS metabolism, Food Chemistry, 2024, 443: 138545.