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Glutamine (Gln)

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CONVENTIONAL UNITS

(Most Abundant Plasma Amino Acid – Central to Nitrogen Transport, Immune Function & Metabolic Homeostasis)

Synonyms

  • Glutamine
  • L-Glutamine
  • Gln
  • Plasma glutamine
  • Amino acid "Q" (genetic code notation)

Units of Measurement

  • µmol/L
  • mg/L
  • mg/dL
  • mg/100 mL
  • mg%
  • µg/mL

Key Conversions

(Molecular Weight ≈ 146.15 g/mol)

1 mg/L = 6.84 µmol/L
1 mg/dL = 68.4 µmol/L
1 µg/mL = 1 mg/L
mg/dL = mg% = mg/100 mL
1 µmol/L = 0.146 mg/L

Description

Glutamine is the most abundant amino acid in human plasma and muscle, accounting for >50% of free amino acids in the body.

Key functions:

  • Major carrier of nitrogen between tissues
  • Critical for immune cells, enterocytes, and renal ammoniagenesis
  • Precursor for nucleotides, glutamate, and GABA
  • Important for acid–base balance, especially during acidosis

Plasma glutamine levels help evaluate metabolic stress, critical illness, urea cycle disorders, and nutritional status.

Physiological Role

1. Nitrogen Transport

Carries ammonia safely as glutamine → prevents toxic buildup.

2. Immune Function

Fuel for:

  • Lymphocytes
  • Macrophages
  • Neutrophils

Low glutamine impairs immune response.

3. Gut & Mucosal Integrity

Enterocytes use glutamine as their primary energy source.

4. Acid–Base Balance

Kidneys convert glutamine → ammonium (NH₄⁺) to excrete acid load.

5. Neurotransmitter Metabolism

Part of the glutamate–glutamine cycle in brain astrocytes.

Clinical Significance

High Glutamine (Hyperglutaminemia)

1. Urea Cycle Disorders (Key Use)

  • CPS1 deficiency
  • OTC deficiency
  • ASS/ASL defects
  • ARG1 deficiency
    Hyperammonemia → ↑ glutamine due to detoxification mechanism.

Glutamine often >1000 µmol/L in severe cases.

2. Hyperammonemia of Any Cause

Liver failure
Reye syndrome
Valproate toxicity

3. Metabolic Disorders

Some organic acidemias increase glutamine.

4. Parenteral Nutrition Overload

Excessive exogenous amino acid infusion.

Low Glutamine (Hypoglutaminemia)

Common in critical illness.

Causes:

  • Severe sepsis & septic shock
  • Trauma, burns
  • Major surgery
  • Malnutrition
  • Short bowel syndrome
  • Catabolic states
  • Chronic GI disease
  • Overutilization by immune cells

Low glutamine is associated with:

  • Immune dysfunction
  • Impaired wound healing
  • Higher ICU mortality (observational data)

Reference Intervals

(Tietz 8E + Mayo + ARUP + ICU nutrition guidelines)

Plasma Glutamine

  • 400 – 700 µmol/L (adults)
  • Newborns: 350 – 800 µmol/L

Critical Ranges

  • >900–1000 µmol/L → Suggest urea cycle defect or severe hyperammonemia
  • <300 µmol/L → Severe stress, sepsis, or malnutrition

Diagnostic Uses

1. Urea Cycle Disorder Screening (Primary Use)

Glutamine rises with:

  • Hyperammonemia
  • Urea cycle blockages
    Interpreted with:
  • Glutamate
  • Citrulline
  • Arginine
  • Ornithine
  • Plasma ammonia

2. Critical Illness & ICU Nutrition

Low glutamine is common in:

  • Sepsis
  • ARDS
  • Burns
  • Multi-organ failure

Used to monitor catabolic state and parenteral nutrition adequacy.

3. Metabolic Evaluations

Part of plasma amino acid profile for:

  • Organic acidurias
  • Mitochondrial disorders
  • Inborn errors of metabolism

4. GI Disease & Malnutrition

Low levels seen in:

  • Crohn’s
  • Ulcerative colitis
  • Short bowel
  • Severe malnutrition

Analytical Notes

  • Fasting plasma, kept on ice immediately
  • Deproteinization prevents post-collection metabolism
  • Avoid serum (platelets release glutamine and glutamate)
  • Analyze by HPLC or tandem mass spectrometry
  • Samples degrade rapidly at room temperature

Clinical Pearls

  • High glutamine + high ammonia strongly suggests urea cycle defects.
  • In sepsis, plasma glutamine is often low, not high.
  • Glutamine supplementation in ICU remains controversial (not routinely recommended).
  • Glutamine:glutamate ratio is more informative than either alone.
  • Elevated glutamine without hyperammonemia may indicate nutritional excess or metabolic derangement.

Interesting Fact

Glutamine is so abundant that it makes up 20–25% of all free amino acids in the body, acting as the primary nitrogen reservoir.

References

  1. Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Amino Acids.
  2. ACMG Guidelines - Urea Cycle Disorder Diagnosis.
  3. Mayo Clinic Laboratories - Plasma Amino Acids.
  4. ARUP Consult - Hyperammonemia Workup.
  5. ESPEN/ASPEN ICU Nutrition Guidelines.
  6. MedlinePlus / NIH - Amino Acid Testing.

Last updated: January 26, 2026

Reviewed by : Medical Review Board

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