The most abundant free amino acid in the human body — a nitrogen taxi, an energy source for fast-dividing cells, and a critical player in brain chemistry.
Symbol
Gln · Q
Discovered
1883
Mol. Weight
146.15 g/mol
Essential
Conditionally
Q
Discovery: From Sugar Beet Juice
L-Glutamine
In 1883, German chemist Ernst Schulze, together with his colleague Ernst Bosshard — the same Schulze who would later discover arginine — was analyzing the pressed juice of sugar beets, searching for nitrogen-containing compounds. He isolated a new amino acid with a long side chain ending in an amide group, structurally almost identical to glutamic acid but with the critical difference of that terminal –CONH₂ instead of –COOH. He named it glutamine. It was later found to occur in abundance in wheat gliadin as well.
The relationship to glutamic acid is direct: glutamine is glutamic acid with an extra amide group. One enzyme converts glutamate to glutamine (glutamine synthetase), another reverses it (glutaminase). This interconversion turns out to be one of the most heavily regulated reactions in all of biochemistry — glutamine sits at a critical junction as the primary molecule the body uses to store and transport nitrogen safely between organs. The synthesis of glutamine from ammonium and glutamate was fully described by Hans Krebs in 1935, using guinea pig and rat kidney tissue.
🚕 Glutamine as Nitrogen Taxi
Ammonia (NH₃) is toxic — even small amounts in the bloodstream damage brain tissue. Yet nitrogen is constantly being released as cells break down proteins. The body's solution is to immediately attach that nitrogen to glutamate, creating glutamine. Glutamine then safely carries the nitrogen through the blood to the liver or kidneys, where it's offloaded for disposal. Without glutamine acting as a non-toxic nitrogen carrier, protein metabolism would be dangerous at every step.
Identifiers and Properties of Glutamine
Identity
IUPAC Name(2S)-2,5-Diamino-5-oxopentanoic acid
FormulaC₅H₁₀N₂O₃
Mol. Weight146.15 g/mol
CAS Number56-85-9
MDL NumberMFCD00008044
Physical
Melting point185 °C
Solubility35 g/L (20 °C)
pKa₁ (COOH)2.17
pKa₂ (NH₃⁺)9.13
pI5.65
Rf (BuOH/AcOH/H₂O = 12:3:5)0.13
Identifiers
Canonical SMILESC(CC(=O)N)C(C(=O)O)N
Isomeric SMILESC(CC(=O)N)[C@@H](C(=O)O)N
InChIKeyZDXPYRJPNDTMRX-VKHMYHEASA-N
CategoryPolar
EssentialConditional
The Most Abundant Free Amino Acid
Most amino acids in the body exist bound inside proteins. Glutamine is unusual: it circulates in enormous quantities as a free molecule in the blood and muscles. At any given moment, roughly 60% of the free amino acid pool in human muscle tissue is glutamine. The plasma concentration of glutamine is higher than any other amino acid — typically 500–900 μmol/L, compared to a few dozen for most others.
This abundance isn't accidental. Glutamine is in constant demand. It is the primary fuel for rapidly dividing cells — intestinal epithelial cells, immune cells, and cancer cells all preferentially consume glutamine for energy rather than glucose. During illness, injury, or intense physiological stress, glutamine demand can exceed the body's ability to synthesize it, which is why it is classified as conditionally essential.
Glutamine and the Brain
One of glutamine's most important roles is in the brain's neurotransmitter cycle. After glutamate (an excitatory neurotransmitter) is released at a synapse and does its signaling work, it needs to be recycled. Glial cells surrounding neurons take up released glutamate and convert it to glutamine (using glutamine synthetase). The glutamine is then transferred back to neurons, which convert it back to glutamate (using glutaminase). This glutamate–glutamine cycle is a continuous loop that maintains the brain's supply of its most important excitatory signal.
Functions of L-Glutamine in the Body
Glutamine participates in a wide range of metabolic processes beyond nitrogen transport. Below are its principal functions.
Gastrointestinal tract integrity
Glutamine is the primary energy source for the rapidly dividing epithelial cells that line the gut wall. These cells have a very high metabolic rate and cannot rely on glucose alone — they consume glutamine preferentially to maintain the structural integrity of the intestinal barrier. This barrier function is critical for preventing the passage of bacteria and toxins from the gut lumen into the bloodstream. Under conditions of illness, surgery, or severe physiological stress, when glutamine levels drop, intestinal permeability can increase significantly.
Immune function
Lymphocytes and macrophages — the primary cells of the adaptive and innate immune response — use glutamine as a major energy substrate, much as they use glucose. Adequate glutamine supply is necessary for the proliferation and activation of immune cells during infection or injury. Glutamine availability directly influences the rate at which the immune system can mount and sustain a response.
Gluconeogenesis
When the body requires additional glucose — during fasting, prolonged exercise, or hypoglycemia — glutamine can be converted to glucose in the liver and kidneys through gluconeogenesis. It is one of the most important amino acid precursors for hepatic and renal glucose production, contributing to the maintenance of stable blood glucose levels.
Conditional essentiality and stress response
Under normal conditions, the body produces sufficient glutamine in the muscles and lungs. However, during severe illness, major surgery, or prolonged intense physical stress, demand can outpace synthesis. One mechanism for this is the stress hormone cortisol: elevated cortisol levels — as seen in acute illness or intensive exercise — accelerate the breakdown of muscle protein and deplete intramuscular glutamine stores. In such conditions, dietary or supplemental glutamine becomes clinically relevant.
Did You Know?
Glutamine makes up around 60% of all free amino acids circulating in muscle tissue — more than all other free amino acids combined. No other amino acid dominates its pool so completely.
Interesting Facts
🔤
Why Q? Glutamine's one-letter code is Q — not an obvious choice from the name. G was already taken (glycine), L was taken (leucine), and U was avoided because it could be confused with uracil. Q was chosen partly because it is rare and unused, and partly because it vaguely echoes the sound of "glutamine" in some phonetic systems. It remains one of the more whimsical assignments in biochemical nomenclature.
🔬
Favored by cancer cells. Many cancer cells consume glutamine at a dramatically accelerated rate — a phenomenon called glutamine addiction. Cancer metabolism is often reprogrammed to use glutamine not just for energy but as a carbon and nitrogen source for building new cellular components. This makes glutamine metabolism an active area of cancer research, with several experimental drugs targeting glutaminase, the enzyme that breaks glutamine down.
🏭
Produced in large quantities industrially. Glutamine is one of the most commercially produced amino acids, synthesized by bacterial fermentation for use in food science, pharmaceuticals, and cell culture media. Growing cells in a laboratory — for biotechnology, vaccine production, or research — typically requires glutamine-supplemented media because cells in culture consume it rapidly.
🧬
Key role in polyglutamine diseases. Some genetic disorders, including Huntington's disease, are caused by abnormally long stretches of repeated glutamine residues (polyglutamine tracts) in proteins. When these glutamine repeats exceed a threshold length, the protein misfolds and aggregates, killing neurons. The precise mechanism of polyglutamine toxicity remains an active area of research.
Where Glutamine Is Found
As a conditionally essential amino acid, glutamine is synthesized by the body but is also richly available in both animal and plant foods. Values below are approximate per standard serving:
