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L-Glutamine, known as L-Glutamin in Turkish, is a proteinogenic α-amino acid with the molecular formula C₅H₁₀N₂O₃. L-Glutamine, defined by CAS No 56-85-9; It is an important nitrogen carrier and amino acid raw material used in food, nutritional supplements, sports nutrition, clinical nutrition, pharmaceutical grade amino acid systems, cell culture and biotechnology applications.
The L-Glutamine molecule carries a α-amino group, a carboxylic acid group, and a carboxamide function in the side chain. This amide group is the main structural element that distinguishes L-Glutamine from L-Glutamic Acid and has a direct impact on the biological role of the molecule in nitrogen metabolism.
The molecular weight of L-Glutamine is approximately 146.14 g/mol. The molecule has a single chiral center and the form used in natural protein synthesis is L-configuration. It can be systematically described as (2S)-2,5-diamino-5-oxopentanoic acid or L-2-aminoglutaramic acid.
Since L-Glutamine can be synthesized in the human body, it is not classified as an essential amino acid in all conditions in the classical sense. However, in some cases such as severe metabolic stress, trauma, critical illness or high tissue demand, the requirement can exceed the synthesis capacity, so it can be defined as a "conditionally essential", that is, conditionally essential amino acid.
In addition to participating in protein synthesis, L-Glutamine is an important metabolic intermediate component that contributes to the transport of nitrogen between tissues, nucleotide biosynthesis, amino sugar formation, glutamate and glutathione metabolism, and energy/carbon metabolism of rapidly proliferating cells.
L-Glutamine has been identified as a nutrient supplement, flavor enhancer, and flavoring agent/adjuvant in the food industry. The U.S. FDA lists L-Glutamine under these technical functions with CAS 56-85-9 and references 21 CFR 172.320. L-Glutamine is an alpha-amino acid, one of the 20 amino acids that make up proteins.
L-Glutamine is a non-essential amino acid and is also the most abundant amino acids in the human body.
L-Glutamine is involved in many important biological processes. For example, as a key amino acid, it is a building block for protein synthesis; it is used in the biosynthesis of urea and purines for nucleic acid synthesis; it is a substrate for the biosynthesis of neurotransmitters; it is also an important source of cellular energy production.
Food, supplement, pharmaceutical, cell culture, and laboratory grades for L-Glutamine may contain the same molecule but are not the same grade grade. Assay, stereochemical purity, microbiological quality, endotoxin, heavy metals, particle structure, cell culture suitability, and pharmacopoeia criteria may vary depending on the area of use.
L-Glutamine exists in the form of a white crystal or crystalline powder. The FCC describes the product as soluble in water and practically insoluble in alcohol and ether. PubChem reports a water solubility of 41.3 g/L at about 25 °C; hence, the solubility of L-Glutamine is lower than that of some amino acids, such as L-Threonine.
One of the technically important features of L-Glutamine is that it exhibits limited chemical stability in aqueous solution. Especially under the influence of time, temperature and pH, glutamine solution can degrade. Therefore, more stable peptide derivatives such as L-Alanyl-L-Glutamine or Glycyl-L-Glutamine can also be used in controlled liquid systems such as cell culture and parenteral nutrition.
When purchasing L-Glutamine, only the expression "99% glutamine" should not be considered. According to the target application, assay, L-isomer identity, loss on drying, residue on ignition, heavy metal and microbiology limits, pharmacopoeia/FCC compliance, cell culture quality system, production method and batch COA results should be evaluated together.
L-Glutamine provides many benefits to the body, such as improving gastrointestinal health, helping treat ulcers and leaky gut, promoting muscle growth, improving diabetes and blood sugar, and aiding in cancer treatment.
L-Glutamine is one of the 20 amino acids encoded by the standard genetic code.
It is not considered an essential amino acid, but it can become conditionally essential in certain situations, including intense athletic training or certain gastrointestinal disorders.
The L-Glutamines side chain is an amide formed by replacing the side chain hydroxyl of glutamic acid with an amine functional group, making it the amide of glutamic acid.
Its codons are CAA and CAG.
In human blood, glutamine is the most abundant free amino acid, with a concentration of about 500-900 μmol/l.
L-Glutamine is odorless but has a slightly sweet taste, L-glutamine plays an important role in DNA synthesis and supports the immune system through glutathione synthesis.
L-Glutamine is an amino acid that plays a crucial role in many biological processes in the human body.
L-Glutamine is considered a conditionally essential amino acid, meaning that under normal circumstances, the body can produce enough, but during times of stress, illness, injury, or intense physical activity, the body's demand for glutamine may exceed its ability to produce it.
WHAT IS L-GLUTAMINE?
L-Glutamine is α-amino acid with L-configuration used in natural protein synthesis.
L-Glutamine is the most naturally abundant, non-essential amino acid in the human body and one of the few amino acids that can directly cross the blood-brain barrier.
It circulates in the blood throughout the body as well as is stored in skeletal muscles. L-Glutamine becomes conditionally essential in cases of illness or injury (requiring it to be obtained from food or supplements).
Dietary sources of L-glutamine include beef, chicken, fish, eggs, milk, dairy products, wheat, cabbage, beets, beans, spinach, and parsley.
Small amounts of free L-glutamine are also found in vegetable juices. Chemically, it is the γ-amide derivative of glutamic acid.
Dietary sources of glutamine include protein-rich foods such as beef, chicken, fish, dairy products, eggs, vegetables such as beans, beets, kale, spinach, carrots, parsley, vegetable juices, as well as fermented foods such as wheat, papaya, Brussels sprouts, celery, kale, and miso.
The one-letter symbol Q for glutamine was assigned in alphabetical order to N for asparagine, being greater only by a methylene –CH2– group.
It can be considered as the amidated form of the terminal carboxylic acid group in the glutamic acid side chain. Therefore, two nitrogen atoms are present in the molecule. The first nitrogen is in the α-amino group.
L-Glutamine is the most abundant amino acid in the body.
L-Glutamine is made in the muscles and is transferred through the blood to different organ systems.
L-Glutamine is a building block for making proteins in the body.
L-Glutamine is also needed to make other amino acids and glucose.
L-Glutamine supplements can help with gut function, immune function, and other processes, especially during times of stress when the body is using more glutamine.
L-Glutamine is a α-amino acid used in the biosynthesis of proteins. The second nitrogen is in the carboxamide group on the side chain.
L-Glutamine's molecular formula is C₅H₁₀N₂O₃, Molecular weight is about 146.14 g/mol, CAS No is 56-85-9, EC/EINECS No is 200-292-1, PubChem CID is 5961, UNII code is 0RH81L854J.
L-Glutamine is a proteinogenic amino acid. This expression means that it is directly incorporated into the protein chain through the genetic code during ribosomal protein synthesis.
Human metabolism can synthesize glutamine. One of the main synthesis reactions is the conversion of glutamate and ammonium to glutamine through the enzyme glutamine synthetase.
Therefore, L-Glutamine is not a mandatory essential amino acid in classical nutritional classification.
However, in some physiological and clinical conditions, the demand for glutamine may increase markedly.
This has led to the use of the phrase "conditionally essential amino acid".
L-Glutamine is central to nitrogen metabolism in the body.
The amide nitrogen in the side chain can act as a transportable nitrogen source between tissues.
This property contributes to the transport of nitrogen in a safer chemical form, limiting the toxic effect of free ammonia.
L-Glutamine can also act as a nitrogen donor in the biosynthesis of purine and pyrimidine nucleotides. It plays a role in the synthesis of amino sugar. It participates in the formation of glutamate.
Although L-Glutamine is important in cell culture, it is less stable in aqueous media than many other amino acids.
Degradation depends on time, temperature, and pH.
For this reason, it is not preferred to keep the ready-made L-Glutamine solution at high temperature for a long time.
COMMON PRODUCT AND CHEMICAL NAMES
L-Glutamine
L-Glutamine
Glutamine
L-2-Aminoglutaramic Acid
(2S)-2,5-Diamino-5-oxopentanoic Acid
Gln
L-Gln
CAS 56-85-9
EC 200-292-1
CAS NO, EC / EINECS NO AND CHEMICAL IDENTIFICATION
Product Name: L-Glutamine
English name: L-Glutamine
Chemical name: L-2-Aminoglutaramic Acid
Systematic name: (2S)-2,5-Diamino-5-oxopentanoic Acid
Chemical class: α-Amino acid
Subclass: Proteinogenic polar amino acid
CAS No: 56-85-9
EC/EINECS No: 200-292-1
PubChem CID: 5961
UNII: 0RH81L854J
Molecular formula: C₅H₁₀N₂O₃
Molecular weight: Approximately 146.14 g/mol
Natural configuration: L
Number of chiral centers: 1
Sidechain functional group: Carboxamide
Physical form: White crystal or crystalline powder
Water solubility: Approx. 41.3 g/L, 25 °C
Water solubility for 1 g: Approx. 20.8 mL of water, 30 °C
pKa1: Approximately 2.17
pKa2: Approximately 9.13
pH: Approx. 5–6, 25 °C in 14.6 g/L solution
Melting/decomposition: About 185°C
Solubility in alcohol: Practically insoluble
Solubility in ether: Practically insoluble
Form at room temperature: Solid
Volatility: Very low
Main functions: Amino acid source, nutrient supplement, cell culture nutrient ingredient and pharmaceutical/nutritional raw material
CHEMICAL STRUCTURE AND MOLECULAR PROPERTIES OF L-GLUTAMINE
At the center of L-Glutamine's structure is a α-carbon.
The amino group is attached to this carbon. The carboxylic acid group is attached.
A hydrogen atom is bonded.
The sidechain is -CH₂-CH₂-CONH₂. The terminal group of the sidechain is carboxamide.
In this amide group, carbonyl oxygen is the hydrogen bond acceptor. The amide NH₂ group can act as a hydrogen bond donor.
α-amino and carboxyl functions enable the molecule to gain ionic character in aqueous media. Therefore, L-Glutamine shows high polarity.
PubChem data support that the lipophilicity of L-Glutamine is very low.
This property is the reason for the low solubility in hydrophobic solvents and significantly higher solubility in the aquatic environment.
However, the water solubility of crystalline L-Glutamine is not unlimited.
A value of 41.3 g/L has been reported at approximately 25 °C. Solubility may increase when temperature increases.
PubChem sources indicate that 1 g of glutamine dissolves in 38.5 mL of water at approximately 18 °C and approximately 20.8 mL of water at 30 °C.
This temperature dependence is important in concentrated stock solutions.
When the hot prepared concentrated solution is cooled, crystal formation can be seen.
The solid crystalline form of L-Glutamine is more stable than aqueous solution.
Chemical transformations of the side chain amide group can occur in aqueous media. Under cell culture conditions, L-Glutamine may break down over time, contributing to the formation of ammonia.
Therefore, the shelf life of cell culture media and glutamine stability in terms of cell toxicity is an important parameter.
More stable dipeptides containing glutamine have been developed to reduce this problem.
L-Alanyl-L-Glutamine is one of the most common examples.
The presence of a USP monograph of L-Alanyl-L-Glutamine also indicates the importance of this derivative in controlled pharmaceutical and supplement applications.
The prominent properties of L-Glutamine at the molecular and biochemical level are as follows:
α-Carrying amino acid structure
Participate in protein synthesis
Moving carboxamide on sidechain
Containing two nitrogen atoms
Contributing to nitrogen transport
Supplying nitrogen to nucleotide synthesis
Participating in glutamate metabolism
Contributing to glutathione metabolism
Being a metabolic substrate in cell culture
Being soluble in water
To be able to degrade over time in aqueous solution
Demonstrate zwitterionic structure
PHYSICAL AND CHEMICAL PROPERTIES OF L-GLUTAMINE
L-Glutamine is a white crystalline solid under normal conditions.
It interacts strongly with water due to the polar amino, carboxyl and amide functions of the molecule.
General technical specifications:
Physical appearance: White crystal or crystalline powder
Chemical class: α-Amino acid
Molecular formula: C₅H₁₀N₂O₃
Molecular weight: Approximately 146.14 g/mol
CAS No: 56-85-9
EC No: 200-292-1
PubChem CID: 5961
UNII: 0RH81L854J
Natural stereochemistry: L
Water solubility: Approx. 41.3 g/L, 25 °C
Approximate solubility at 30 °C: 1 g / 20.8 mL water
Approximate solubility at 18 °C: 1 g / 38.5 mL of water
Approximate solubility at 0 °C: 1 g / 56.7 mL of water
Methanol solubility: Very low
Ethanol solubility: Very low
Ether solubility: Practically insoluble
Benzene solubility: Practically insoluble
Acetone solubility: Practically insoluble
Solubility of ethyl acetate: Practically insoluble
Chloroform solubility: Practically insoluble
pKa1: Approximately 2.17
pKa2: Approximately 9.13
pH in 14.6 g/L solution: Approx. 5–6.25 °C
Melting/decomposition: About 185°C
Volatility at room temperature: Very low
General GHS classification: Unclassified in the PubChem registry
USP assay range: 98.5–101.5%, on dry basis
Some of these values refer to the general physical properties of pure L-Glutamine.
Assay, loss on drying, residue on ignition, heavy metals and microbiological limits depend on the quality standard used and the manufacturer.
A manufacturer's supplement-grade product specifications should not be generalized to all L-Glutamine commercial products.
Likewise, cell culture quality endotoxin or sterility requirements are not standard requirements for food-grade L-Glutamine.
HOW DOES L-GLUTAMINE WORK AT THE MOLECULAR LEVEL?
The biological role of L-Glutamine is related both as an amino acid participating in protein synthesis and as one of the important intermediate components of carbon and nitrogen metabolism.
In protein synthesis, L-Glutamine is incorporated into the polypeptide chain via the aminoacyl-tRNA mechanism.
Apart from this, it can be used as a nitrogen donor in metabolic reactions to free glutamine.
Amide nitrogen to glutamine can be used in the synthesis of purine nucleotides.
Pyrimidine can also provide nitrogen to glutamine in its synthesis pathways.
Glutamine is an important source of nitrogen in the production of amino sugar.
Glutamine can be converted to glutamate by glutaminase reaction.
Glutamate can then participate in different amino acid and energy metabolism pathways.
Therefore, L-Glutamine acts as both an amino acid and a metabolic substrate in a cell culture medium.
The high need for nucleotides in rapidly proliferating cells may increase the demand for glutamine.
This feature is very important in terms of cell culture.
Thermo Fisher states that L-Glutamine participates in purine and pyrimidine nucleotide, amino sugar, glutathione, glutamate and other amino acids, and in protein synthesis.
However, L-Glutamine is not stable in solution.
Degradation due to time, temperature and pH can lead to both a decrease in glutamine concentration and an increase in by-products in cell culture.
Therefore, ready-made media manufacturers can use more stable glutamine dipeptides.
In nutritional applications, the working principle of L-Glutamine is to provide usable glutamine in the biological system.
However, since the body can synthesize glutamine in healthy individuals, the effect of supplement use is not the same in all cases.
Therefore, it is not scientifically and legislatively correct to describe L-Glutamine with precise medical phrases such as general-purpose "muscle building", "immune booster" or "gut healer".
The physiological function of the product must be distinguished from the clinical benefit claim of a particular supplement product.
The main functions of L-Glutamine at the molecular and metabolic level are:
Participate in protein synthesis
Contributing to nitrogen transport
Supplying nitrogen to Purine synthesis
Contributing to the synthesis of pyrimidine
Contributing to the synthesis of amino sugar
Being a source of glutamate
Contributing to glutathione metabolism
Being a metabolic substrate in cell culture
Supporting the nutrient needs of rapidly proliferating cells
Providing a source of glutamine in nutrition and supplement systems
IN WHICH SECTORS IS L-GLUTAMINE USED?
L-Glutamine is a versatile amino acid used in the food, nutritional supplement, clinical nutrition, pharmaceutical, biotechnology, and laboratory sectors.
Main areas of use:
Nutritional supplements
Amino acid powders
Sports nutrition products
Protein/amino acid blends
Food-grade amino acid premixes
Special nutritional products
Medical nutrition systems
Enteral nutrition research
Pharmaceutical amino acid products
Parenteral nutrition components
Glutamine dipeptide systems
L-Alanyl-L-Glutamine products
Glycyl-L-Glutamine products
Cell culture media
Mammalian cell culture
Biopharmaceutical production environments
Biotechnological fermentation environments
Laboratory reagents
Amino acid solutions for research purposes
Tissue culture media
Microbial media
Food flavour systems
Nutrient fortification applications
The grade in which L-Glutamine is used should be changed according to the target sector.
Food-grade L-Glutamine is not automatically suitable for cell culture.
Cell-culture grade product is also not considered to be produced according to food legislation.
USP/EP or other pharmacopoeia and GMP requirements for pharmaceutical grade should be checked separately.
FOOD, NUTRITIONAL SUPPLEMENT AND SPORTS NUTRITION APPLICATIONS OF L-GLUTAMINE
L-Glutamine can be used as a source of amino acids in the food and nutritional supplement industry.
The FDA lists L-Glutamine as a nutrient supplement, flavor enhancer, and flavoring agent/adjuvant.
It is registered as FEMA No. 3684.
It is also defined as JECFA flavor number 1430.
Here are the possible functions of L-Glutamine in food applications:
Providing amino acid nutritional support
Completing the composition of amino acid mixtures
Being an active ingredient in nutritional supplement powders
Being an amino acid component in sports nutrition products
Adding free amino acids to protein shakes
Providing a source of glutamine in specialized nutrition systems
To perform auxiliary technical functions in flavor systems
For use in nutrient fortification applications
In powder supplement applications, L-Glutamine is often used in dry form.
The solid form can provide higher chemical stability than the aqueous solution.
Instant powder systems mixed with water before consumption are therefore common.
Since L-Glutamine has a water solubility of about 41 g/L at room temperature, the solubility limit should be considered in very high concentration beverage targets.
For example, when a small volume of very high weight glutamine solution is desired, sediment or undissolved crystal may be seen.
As the temperature increases, the solubility may increase, but the final product should not be kept at high temperature for a long time.
In terms of taste, L-Glutamine may be relatively neutral to some other amino acids, but the final sensory profile should be considered in conjunction with other amino acids, acids, flavoring, and flavorings.
A single universal technical percentage should not be given for the usage rate in supplement formulation.
Portion size, target daily use, product claims, and target market legislation should be considered together.
No pharmaceutical treatment claims should be made in the food or supplement product.
USE OF L-GLUTAMINE IN CELL CULTURE, BIOTECHNOLOGY, AND PHARMACEUTICAL APPLICATIONS
L-Glutamine is one of the most common amino acid components of cell culture media.
It serves as a metabolic substrate in mammalian cell cultures.
It participates in protein synthesis.
It supports nucleotide synthesis.
It contributes to glutamate and glutathione metabolism.
For this reason, many basal medium and supplement systems contain glutamine or require it to be added to glutamine separately.
In cell culture applications, concentration is usually expressed at the mM level.
Thermo Fisher offers stock solutions of 200 mM L-Glutamine commercially.
The actual final concentration is determined by the cell line and medium protocol used.
The important technical problem here is that glutamine is unstable in solution.
Thermo Fisher clearly states in its current user guide that the rate of degradation depends on time, temperature and pH.
For this reason, cell-culture stock solution is mostly stored frozen or stored in a controlled manner at low temperature.
It is not recommended to leave it completely dissolved for a long time at high temperature.
Concentrated solutions such as 200 mM can crystallize when cooled.
This precipitate may not imply chemical degradation.
With short-term controlled heating, the crystals can be re-dissolved.
However, keeping the solution warm for extended periods can adversely affect stability.
In pharmaceutical and parenteral nutrition applications, the aqueous stability problem of L-Glutamine is even more important.
Therefore, glutamine can be supplied in the form of more stable dipeptide.
L-Alanyl-L-Glutamine is an example of this.
The USP has separate monograph for L-Alanyl-L-Glutamine.
In EMA documents, amino acid infusion systems containing L-Alanyl-L-Glutamine are included in the scope of parenteral nutrition.
Glycyl-L-Glutamine is a similarly defined glutamine dipeptide.
With pure L-Glutamine, the molecular weight, stability and usage calculations of these dipeptides are different.
Direct one-to-one substitution by weight should not be made.
IS L-GLUTAMINE USED IN FOOD, COSMETICS AND PHARMACEUTICAL APPLICATIONS?
L-Glutamine is the defined amino acid that can be used in food and nutritional supplement applications.
It has nutrient supplement and flavoring functions in FDA records.
There is a monograph of L-Glutamine in the Food Chemicals Codex.
For food-grade use, the compliance of the relevant product with the food quality system must also be verified.
L-Glutamine is also widely used in dietary supplement systems.
USP's Glutamine monograph defines a content of 98.5–101.5% on a dry basis.
This value provides a reference for pharmacopoeia quality control.
L-Glutamine can also be used in pharmaceutical and clinical nutrition systems, but there are applications where dipeptide derivatives are used instead of pure glutamine due to aqueous stability.
Meeting the USP assay value alone is not sufficient for pharmaceutical use.
GMP, endotoxin, microbiological quality, sterile manufacturing requirements, and specific preparation legislation should be evaluated separately.
In cosmetic applications, L-Glutamine can be used in amino acid complexes, but its main commercial volume is not cosmetics.
If it is to be used in skin or hair care, INCI should be checked separately for purity and compliance with cosmetic legislation.
The biological importance of L-Glutamine does not mean that a clinical effect has been shown in a particular cosmetic product.
INDUSTRIAL APPLICATIONS OF L-GLUTAMINE
L-Glutamine can be used on an industrial scale as a high-purity crystalline amino acid or as a sterile/filtered solution at a controlled concentration.
The following functions may be prominent in industrial L-Glutamine applications:
Nutritional supplement production
Sports nutrition product production
Amino acid premix preparation
Food-grade nutrient fortification
Tailored nutrition product development
Medical nutrition raw material system
Pharmaceutical amino acid production
Cell culture media production
Biopharmaceutical cell culture
Serum-free medium formulation
Biotechnology processes
Tissue culture
Research environments
Fermentation media
Amino acid reference/analysis systems
Production of glutamine dipeptide
Dry supplement blend production
When L-Glutamine is used in powder form, particle size and flow characteristics are important.
Very fine dust can create high dusting.
Segregation can be seen when dry blend is prepared with raw materials with different bulk density values.
For this reason, mixing validation is important in supplement and premix production.
In the aqueous system, solubility and stability should be evaluated together.
A solubility value of approximately 41.3 g/L, 25 °C, affects the limits of high-concentration stock systems.
A 200 mM L-Glutamine solution theoretically contains approximately 29.2 g/L of glutamine.
Although this concentration is below the room temperature solubility limit, crystallization may occur at low temperature due to solubility decrease.
In the cell culture system, not only the initial glutamine concentration but also the storage time is important.
Loss of glutamine during long-term medium storage can affect process consistency.
The following issues should be evaluated in the use of L-Glutamine in industrial systems:
L-isomer ID
Assay
Stereochemical purity
Loss on drying
Residue on ignition
Heavy metal limits
Arsenic
Lead
Cadmium
Mercury
Microbiological quality
Endotoxin
Bioburden
Sterility if sterility is required
Particle size
Bulk density
Streaming features
Dusting
Water solubility
Solution stability
pH
Storage temperature
Crystallization
Occurrence of ammonia
Cell culture suitability
FCC compliance
USP/EP compliance
GMP requirement
TDS
SDS
COA
WHAT PROBLEMS CAN L-GLUTAMINE HELP SOLVE?
L-Glutamine can help meet various technical needs in food, supplement, and biotechnology systems, such as missing amino acid composition, cell culture nutrient needs, and controlled glutamine supply.
Lack of glutamine in the amino acid mixture
Pure L-Glutamine enables direct adjustment of the target amino acid composition.
The need for glutamine source in sports nutrition powder
Food/supplement-grade L-Glutamine dry powder provides a highly concentrated amino acid supply to the system.
Insufficient glutamine in cell culture medium
By adding L-Glutamine medium in a controlled manner, it can help meet the metabolic needs of the cell.
Long-term loss of glutamine in cell culture medium
In this case, simply adding more L-Glutamine is not always the right solution.
Medium storage time, temperature, and dipeptide alternatives to more stable glutamine should be evaluated.
Precipitation of L-Glutamine stock solution in cold
Temperature drop in concentrated solution may reduce solubility.
Thermo Fisher states that the crystals can be resolved with short-term controlled 37 °C heating and gentle stirring.
Sediment formation in supplement drink
The target concentration of glutamine should be readjusted according to the temperature of the water and the total amount of dissolved solids.
Inhomogeneous active distribution in dry blende
Particle size and bulk density should be matched, and appropriate premixing and mixing validation should be applied.
Low glutamine stability in pharmaceutical aqueous product
More stable derivatives such as L-Alanyl-L-Glutamine or Glycyl-L-Glutamine may be considered.
Not every glutamine-related technical problem can be solved by increasing the amount of L-Glutamine.
Especially in aqueous systems, stability, temperature and time factors should be evaluated together.
THINGS TO CONSIDER WHEN USING L-GLUTAMINE
Quality class, stereochemistry, solubility and aqueous stability are the basic technical criteria in the use of L-Glutamine.
The following issues should be considered when using L-Glutamine:
CAS Number must be verified.
The L-configuration must be verified.
Confusion with D-Glutamine should be avoided.
Assay should be checked.
Food-grade, supplement-grade, pharma-grade or cell-culture grade should be distinguished.
FCC requirement must be verified.
USP/EP requirement should be verified.
Loss on drying should be checked.
Residue on ignition should be checked.
Heavy metal criteria should be examined.
Microbiological quality should be controlled.
Endotoxin should be evaluated in the use of cell culture.
Sterility should be verified in sterile use.
The particle size should be controlled.
Dry blend homogeneity should be tested.
Water solubility should be considered.
Low-temperature crystallization in concentrated solution should be evaluated.
The solution should not be kept at high temperature for a long time.
The effect of pH on stability should be evaluated.
Cell culture medium shelf life should be checked.
TDS should be examined.
SDS should be examined.
The COA must be verified.
The target country's food/supplement legislation should be checked.
The preparation of L-Glutamine solution and the storage of dry powder are not the same stability problem.
The dry crystalline product is more stable in proper storage.
In aqueous solutions, time and temperature monitoring is more important.
Therefore, the production process should be designed not only on the solubility but also on how long the solution will be stored.
INITIAL FORMULATION APPROACHES FOR L-GLUTAMINE
The following examples are initial approaches prepared to show how L-Glutamine can be evaluated in food, supplement and biotechnology applications.
These are not verified commercial formulas, medical dose recommendations, or prescriptions to be transferred directly to mass production.
EXAMPLE 1: L-GLUTAMINE POWDER NUTRITIONAL SUPPLEMENT SOLUBILITY SCREENING
Purpose: To evaluate the dissolution time, clarity, taste, and post-storage behavior of L-Glutamine level in water.
Starting components:
Food/supplement-grade L-Glutamine: 20.0%
Carrier/soluble beverage base: 65.0%
Aroma: 5.0%
Acidity regulator: 3.0%
Sweetener: 2.0%
Other amino acids: 5.0%
Total: 100%
Application approach:
The L-Glutamine assay value is verified via COA.
Target portions are prepared.
A standard volume of 20–25 °C water is used.
The dissolution time is recorded.
Clarity is observed.
Insoluble particles are checked.
Crystallization is observed after holding at 5-10 °C.
Taste panel is applied.
Dry mix moisture stability is monitored.
The final portion level is determined by the legislation and the product concept.
EXAMPLE 2: L-GLUTAMINE CELL CULTURE STOCK SOLUTION STABILITY SCREENING
Purpose: To evaluate the effect of L-Glutamine concentration, storage temperature, and time on solubility/stability.
Starting components:
Cell-culture grade L-Glutamine: 2.92%
Sterile or suitable high purity water: 97.08%
Total: 100%
Target stock concentration: Approx. 200 mM
Suitable sterile filtration system: Used as process equipment
Application approach:
L-Glutamine is dissolved at controlled temperature.
Final concentration is verified.
Proper filtration is applied.
The solution is divided into small aliquots.
A group is stored in frozen conditions.
A group is compared under 2–8 °C conditions.
Clarity is checked at determined time points.
Crystallization is followed.
If necessary, glutamine or ammonia analysis is performed.
Cell culture performance is compared with the reference fresh solution.
The most appropriate storage strategy is determined.
EXAMPLE 3: COMPARISON OF L-GLUTAMINE AND L-ALANYL-L-GLUTAMINE
Objective: To evaluate the difference in the stability of free L-Glutamine and glutamine dipeptide in liquid nutrition or biotechnology system.
Starting components:
System A – Free L-Glutamine solution
Base solution: 97.08%
L-Glutamine: 2.92%
Total: 100%
System B – L-Alanyl-L-Glutamine solution
Base solution: 95.65%
L-Alanyl-L-Glutamine: 4.35%
Total: 100%
pH: Maintained within the same target range in both systems
Storage temperatures: Kept the same in both systems
Application approach:
The two systems are prepared taking into account the glutamine equivalent provided.
Initial active quantities are analytically verified.
Samples are stored at the same temperatures.
At specific time points, the active concentration is measured.
Ammonia or other degradation indicators are followed.
Clarity and crystallization are checked.
Target application performance is compared.
Stability advantage is evaluated together with cost and regulatory requirements.
ALTERNATIVES AND COMPARISON OF L-GLUTAMINE
Biological function, chemical stability, and target application should be considered together when determining the alternative to L-Glutamine.
No other amino acid directly replaces all of L-Glutamine's metabolic functions.
L-GLUTAMINE AND L-GLUTAMIC ACID
L-Glutamine and L-Glutamic Acid are structurally closely related.
Glutamic Acid carries terminal carboxylic acid in its side chain.
L-Glutamine carries carboxamide in the same position.
This difference changes the nitrogen content of the molecule and its acid-base behavior.
L-Glutamine contains two nitrogens, while L-Glutamic Acid contains one.
They can convert to each other in cell metabolism but are not directly the same component in formulation and nutrition.
Exact substitution should not be made by weight.
L-GLUTAMINE AND L-ALANYL-L-GLUTAMINE
L-Alanyl-L-Glutamine is a dipeptide consisting of alanine and glutamine.
It can provide higher stability in aqueous systems compared to pure L-Glutamine.
For this reason, it can be preferred in liquid applications such as cell culture and parenteral nutrition.
Its molecular weight is higher.
The equivalent to glutamine must be calculated.
It should not be substituted directly in the same weight.
L-GLUTAMINE AND GLYCYL-L-GLUTAMINE
Glycyl-L-Glutamine is a dipeptide containing glycine and glutamine.
Like L-Alanyl-L-Glutamine, it can be considered one of the more stable carrier forms of glutamine.
There is a separate monograph in USP.
It is not the same chemical as pure L-Glutamine.
When calculating the amount of dipeptide, the molar equivalent to glutamine it will provide should be taken into account.
L-GLUTAMINE AND L-ASPARAGINE
L-Asparagine is also a proteinogenic amino acid that carries carboxamide in the side chain.
However, its side chain is one carbon shorter than glutamine.
L-Asparagine and L-Glutamine carry different metabolic pathways and protein codings.
While they are both amide amino acids, they are not nutritional or cell culture equivalents of each other.
L-GLUTAMINE AND D-GLUTAMINE
D-Glutamine is the optical enantiomer of L-Glutamine.
The standard form used in protein synthesis is L-Glutamine.
Stereoisomer purity is important in food, supplement, pharmaceutical and cell culture applications.
D-Glutamine is not a direct alternative to standard L-Glutamine raw material.
QUALITY CONTROL AND PURCHASING CRITERIA FOR L-GLUTAMINE
When purchasing L-Glutamine, the target usage area is the first criterion to be determined.
Food-grade, supplement-grade, pharmaceutical-grade and cell-culture grade products should not be evaluated with the same quality specification.
Recommended information to review before purchasing:
Full product name
Manufacturer
L-isomer ID
CAS No
EC No
Molecular formula
Assay
Dry base assay
Specific optical rotation
Stereochemical purity
Loss on drying
Residue on ignition
If sulfated ash is needed
pH
Heavy metal limits
Lead
Arsenic
Cadmium
Mercury
Microbiological limits
Total aerobic load
Yeast and mold
E. coli
Salmonella
Endotoxin, if necessary
Sterility, if necessary
Particle size
Bulk density
Streaming features
Water solubility
Color
Smell
Production method
Fermentation information
If GMO declaration is required
FCC compliance
USP compliance
EP eligibility
Cell culture tested information
GMP certificate
Food safety quality certificates
Shelf life
Packaging
Batch number
Production date
Origin
TDS
SDS
COA
In the USP Glutamine monograph, an assay range of 98.5–101.5% is defined on a dry base.
This value is an important reference in terms of pharmaceutical/dietary supplement quality control.
The FCC also offers a separate food grade monograph for L-Glutamine.
In cell culture application, endotoxin, sterility, cell-culture performance and solution preparation conditions may become more critical.
In the transition to a new supplier, only assay comparison should not be made.
Dissolution rate, particle structure, and stability behavior in liquid systems must also be verified.
STORAGE AND HANDLING OF L-GLUTAMINE
Storage: L-Glutamine should be stored in dry, clean, and tightly sealed packaging.
Humidity control: The powder or crystalline raw material should be protected from unnecessarily high humidity.
Contamination: The risk of cross-contamination in food, supplement and pharmaceutical grades should be controlled within the scope of the quality system.
Odor: It is recommended to keep it separate from strong-smelling chemicals.
Temperature: The manufacturer's recommended warehouse temperature should be used for the dry product.
Solutions: Ready-made L-Glutamine solutions have different stability requirement than dry product.
Cell culture stock solutions are usually stored in low temperature or frozen conditions.
Thermo Fisher's CTS L-Glutamine 200 mM product is stored between -5 °C and -20 °C and protected from light.
This storage condition does not apply to pure dry L-Glutamine, but to certain commercial sterile 200 mM solution.
Keeping the solution completely thawed for a long time, especially at temperatures above 2–8 °C, may reduce stability.
Concentrated stock solutions can crystallize in the cold.
In case of crystal sighting, the exact product manufacturer's re-dissolution instructions should be followed.
Transportation: The exact transportation classification of Dry L-Glutamine should be checked from the product SDS.
For pharmaceutical or cell-culture products, temperature-controlled shipment may also be required.
L-GLUTAMINE SAFETY INFORMATION
L-Glutamine is not a highly volatile substance under normal usage conditions.
In the general register of PubChem, L-Glutamine is not classified as a hazardous substance.
However, unnecessary inhalation of industrial amounts of fine dust should be avoided.
Proper dust control should be used during weighing and transfer.
Intense dust contact with the eyes may cause mechanical irritation.
Normal industrial hygiene practices and appropriate personal protective equipment should be used.
It is reported that in case of high temperature decomposition, degradation products such as nitrogen oxides may be formed.
For this reason, the product should not be unnecessarily raised to thermal decomposition temperature.
For safe use, spillage and storage, the current SDS document of the exact product should be taken as basis.
WHAT SHOULD BE CONSIDERED WHEN BUYING L-GLUTAMINE?
In the supply of L-Glutamine, the end usage area should be determined first.
The quality criteria required for a sports nutrition product are not the same as the requirements of biopharmaceutical cell culture application.
The following information should be clarified before purchasing:
Use sector
Food Application
Nutritional support
Sports nutrition
Medical nutrition
Pharmaceutical
Cell culture
Biotechnology
Laboratory
Desired grade
Minimum assay
L-isomer purity
Loss on drying limit
Heavy metal limit
Microbiological criteria
Endotoxin requirement
Requirement for sterile products
Particle size
Solubility
Pharmacopoeia requirement
FCC requirement
USP requirement
EP requirement
Cell culture tested requirement
GMP certificate
Food safety certifications
Fermentation production information
GMO declaration
Halal or Kosher requirement
Manufacturer
Origin
Packaging
Estimated order quantity
Shelf life
The need for TDS
The need for SDS
The need for COA
The price of L-Glutamine should not be evaluated only on the kilogram cost.
The documentation and production costs of food-grade and high-purity cell-culture or pharmaceutical grade products can be significantly different.
If the liquid is to be used in the system, not only the price of dry raw material, but also the loss of solubility and stability can affect the total process cost.
Derivatives like the more stable L-Alanyl-L-Glutamine can provide long shelf life or process consistency, even with a higher raw material price.
L-GLUTAMINE SUPPLY FROM ATAMAN KIMYA
L-Glutamine; It is a proteinogenic amino acid used in food, nutritional supplements, sports nutrition, special nutrition, pharmaceutical, laboratory and biotechnology applications.
Companies that want to get information about L-Glutamine supply from Ataman Kimya can request information about product suitability, current supply conditions, packaging options and price offer by sharing their usage areas and target quality criteria.
The current stock status, manufacturer, origin, food/supplement/pharma/cell-culture quality class, purity, packaging and technical specifications of the product should be confirmed from Ataman Kimya before ordering.
Sharing the following information in the request for a quote facilitates the evaluation of the right L-Glutamine product:
Use sector
Final application
Need for food-grade, supplement-grade, pharma-grade or cell-culture grade
Minimum assay
Desired physical form
Particle size
Resolution requirement
Microbiological criteria
Heavy metal limits
Endotoxin requirement
Sterility requirement
FCC requirement
USP/EP requirement
GMP requirement
Fermentation/GMO documentation
Halal or Kosher requirement
Estimated order quantity
Type of packaging requested
Requested technical documents
TDS or COA information of the current L-Glutamine product, if applicable
FREQUENTLY ASKED QUESTIONS ABOUT L-GLUTAMINE
What is L-Glutamine?
L-Glutamine is a natural L-configuration proteinogenic α-amino acid used in protein synthesis.
What is the Turkish name of L-Glutamine?
It is called L-Glutamine.
What is the CAS number of L-Glutamine?
CAS No is 56-85-9.
What is the EC number of L-Glutamine?
EC / EINECS No is 200-292-1.
What is the molecular formula of L-Glutamine?
C₅H₁₀N₂O₃.
What is the molecular weight of L-Glutamine?
It is approximately 146.14 g/mol.
Is L-Glutamine a proteinogenic amino acid?
It is one of the standard amino acids used in ribosomal protein synthesis.
Is L-Glutamine an essential amino acid?
It is not essential in the classical sense in healthy conditions; it can be considered conditionally essential in some cases of high metabolic demand.
Is L-Glutamine the same as Glutamic Acid?
L-Glutamine is the amidated derivative of the side chain carboxyl group of glutamic acid.
Is L-Glutamine soluble in water?
PubChem reports a water solubility of 41.3 g/L at about 25 °C.
Is the solubility of L-Glutamine affected by temperature?
At low temperature, solubility decreases and crystallization can be seen in concentrated solutions.
Is L-Glutamine soluble in alcohol?
It practically shows very low resolution.
What is the melting point of L-Glutamine?
The FCC states that it melts by degradation at around 185 °C.
What are the pKa values of L-Glutamine?
Approximately pKa1 is 2.17 and pKa2 is 9.13.
What is the pH of L-Glutamine solution?
PubChem sources have a pH of approximately 5–6, 25 °C in a solution of 14.6 g/L.
Is L-Glutamine used in food?
FDA lists it as a nutrient supplement, flavor enhancer and flavoring agent/adjuvant.
What is L-Glutamine's FEMA number?
FEMA No. 3684.
Is L-Glutamine available FCC?
There is a monograph on L-Glutamine in the FCC.
Is L-Glutamine found in USP?
USP includes the Glutamine monograph.
What is the range of USP Glutamine assay?
It is 98.5–101.5% L-Glutamine on a dry basis.
Is L-Glutamine used in dietary supplement?
It can be used according to the appropriate supplement/food-grade quality and target country legislation.
Is L-Glutamine used in sports nutrition?
It is widely formulated in amino acid and sports nutrition products.
Is L-Glutamine used in cell culture?
It is one of the basic cell culture nutrients that contribute to protein, nucleotide and other biomolecule synthesis pathways.
How stable is L-Glutamine for cell culture?
It is less stable in aqueous solution than many other amino acids, and its rate of degradation depends on time, temperature, and pH.
Why does L-Glutamine stock solution precipitate?
The solubility of the concentrated glutamine solution may decrease at low temperature and crystallization may occur.
Can the crystals in 200 mM L-Glutamine solution be dissolved again?
Although it depends on the manufacturer's instructions, Thermo Fisher recommends short-term heating of about 37 °C and gentle stirring on its product.
Why does L-Glutamine decrease over time in cell culture medium?
It is not chemically stable in aqueous media and can be degraded by the effect of time/temperature/pH.
What is L-Alanyl-L-Glutamine?
It is the dipeptide composed of alanine and glutamine, which can provide higher stability in liquid systems than free L-Glutamine.
What is Glycyl-L-Glutamine?
It is another stable glutamine dipeptide that contains glycine and glutamine.
Can L-Alanyl-L-Glutamine and L-Glutamine be used in the same amount?
Molecular weights and glutamine equivalents are different; molar calculation should be made.
Can L-Glutamine be used as a pharmaceutical raw material?
Pharmaceutical grade products may be available, but not every L-Glutamine product is automatically pharmaceutical grade.
Is L-Glutamine used in parenteral nutrition?
Glutamine source can be used in parenteral nutrition systems; dipeptide forms such as L-Alanyl-L-Glutamine can be widely evaluated due to stability.
Can L-Glutamine be used in cosmetics?
It can be used in amino acid-based cosmetic systems, but its main commercial application is in food, supplements, and biotechnology.
Can L-Glutamine be produced by fermentation?
Microbial fermentation is one of the common methods in commercial amino acid production.
Is L-Glutamine produced with GMO?
The production microorganism and GMO status depend on the manufacturer. Exact should be verified from the product's regulatory document.
Is L-Glutamine the same as D-Glutamine?
They are each other's enantiomers.
Is L-Glutamine the same as L-Asparagine?
While both are amide amino acids, their molecular structures and biological roles are different.
Why is L-Glutamine important in nitrogen metabolism?
Side chain amide nitrogen contributes to the transport and utilization of nitrogen in biochemical reactions.
Does L-Glutamine play a role in the synthesis of purine and pyrimidine?
Glutamine amide nitrogen can be used as a nitrogen source in these biosynthetic pathways.
Is L-Glutamine related to glutathione?
Since glutamine contributes to glutamate metabolism, it is metabolically related to glutathione synthesis pathways.
What quality criteria are important when buying L-Glutamine?
Assay, stereochemical purity, moisture, ash, heavy metal, microbiology and target application-specific quality certificates are important.
What to look for when buying cell culture grade L-Glutamine
In addition to the assay, endotoxin, sterility or bioburden, cell culture suitability and storage conditions of the solution should be evaluated.
What documents should be requested for L-Glutamine?
TDS, SDS, and COA are essential documents. Depending on the application, FCC, USP/EP, GMP, food safety, endotoxin, and cell-culture documents may be requested.
How should L-Glutamine be stored?
The dry product should be stored in closed, dry and clean conditions. The temperature and shelf life of ready-made solutions should be managed according to the exact manufacturer's instructions.
L-GLUTAMINE – TECHNICAL SUMMARY
L-Glutamine, known as L-Glutamine in Turkish, is a natural L-configuration proteinogenic α-amino acid with the molecular formula C₅H₁₀N₂O₃. It has CAS No 56-85-9, EC No 200-292-1, PubChem CID 5961, and a molecular weight of approximately 146.14 g/mol.
L-Glutamine is the amidated derivative of the side chain carboxylic group of glutamic acid. The molecule carries a α-amino group, a carboxylic acid, and a carboxamide side chain.
Since the human body can synthesize L-Glutamine, it is not a continuous essential amino acid in the classical sense. However, it can be considered conditionally essential under certain conditions of high metabolic demand.
In addition to protein synthesis, L-Glutamine is important for nitrogen transport, nucleotide biosynthesis, amino sugar formation, glutamate metabolism and glutathione-related metabolic pathways.
L-Glutamine is white crystal or crystalline powder. PubChem reports a water solubility of 41.3 g/L at about 25 °C, a pKa of about 2.17 and 9.13, and a pH of about 5–6 in a solution of 14.6 g/L.
The FCC states that L-Glutamine is soluble in water, practically insoluble in alcohol and ether, and dissolves by degradation around 185 °C.
The FDA lists L-Glutamine as a nutrient supplement, flavor enhancer, and flavoring agent/adjuvant. FEMA No. 3684 and 21 CFR 172.320 reference registered.
The USP Glutamine monograph defines an assay range of 98.5–101.5% on a dry base. Therefore, pharmacopoeia compliance can be verified separately in supplement and pharmaceutical-grade purchases.
L-Glutamine is an important nutrient in cell culture. It contributes to protein and nucleotide synthesis and various metabolic pathways.
The important technical limitation of free L-Glutamine is that it can be degraded in aqueous solution by the action of time, temperature and pH. Low-temperature crystallization can also be seen in concentrated solutions.
In systems where higher fluid stability is required, glutamine dipeptides such as L-Alanyl-L-Glutamine or Glycyl-L-Glutamine may be considered.
Even if food-grade, supplement-grade, pharmaceutical-grade and cell-culture grade products have the same CAS number, the quality requirements are not the same. Assay, stereochemistry, microbiology, heavy metals, endotoxin and regulatory documents should be checked separately for exact use.
Companies planning to supply L-Glutamine from Ataman Kimya are recommended to confirm the current product and offer conditions by sharing the end usage area, target quality class, minimum assay, particle characteristics, pharmacopoeia or FCC requirement, quantity and technical document needs.
