Unit Converter
Glutamic Acid (Glu)
(Non-Essential Amino Acid – Central to Nitrogen Metabolism, Neurotransmission & IEM Screening)
Synonyms
- Glutamate (when ionized)
- Glutamic acid
- L-Glutamate
- Glu
- Plasma glutamate
Units of Measurement
- µmol/L
- mg/L
- mg/dL
- mg/100 mL
- mg%
- µg/mL
Key Conversions
(Molecular Weight ≈ 147.13 g/mol)
1 mg/L = 6.80 µmol/L
1 mg/dL = 68.0 µmol/L
1 µg/mL = 1 mg/L
mg/dL = mg% = mg/100 mL
1 µmol/L = 0.147 mg/L
Description
Glutamic acid (glutamate) is a non-essential amino acid and the body’s most abundant excitatory neurotransmitter.
It plays essential roles in:
- Nitrogen transport
- Amino acid metabolism
- Ammonia detoxification
- Urea cycle linkage
- Brain neurotransmission
- Precursor to γ-aminobutyric acid (GABA)
Plasma glutamate levels are clinically relevant mainly in inborn errors of metabolism, liver disease, and nutritional assessment.
Physiological Role
1. Neurotransmitter Function
Glutamate is the primary excitatory neurotransmitter in the CNS.
Involved in:
- Learning & memory (NMDA receptor)
- Synaptic plasticity
- Neuronal development
2. Amino Acid Metabolism
- Central molecule in amino group transamination
- Precursor for alanine, aspartate, proline, glutamine
- Key part of the glutamate–glutamine cycle
3. Detoxification
- Converts ammonia to glutamine (glutamine synthetase)
- Helps maintain nitrogen balance
4. Energy Pathways
Converted to:
- α-ketoglutarate → enters Krebs cycle
Clinical Significance
High Glutamic Acid (Hyperglutamatemia)
Seen in metabolic and hepatic disorders.
1. Inborn Errors of Metabolism (IEM)
Most significant diagnostic use.
- Glutamate dehydrogenase deficiency (rare)
- Pyridoxine-dependent epilepsy
- Urea cycle defects (e.g., CPS, OTC deficiencies)
- Hyperinsulinism-hyperammonemia (HI/HA) syndrome
- Maple syrup urine disease (indirect effect)
- Mitochondrial disorders
2. Liver Disease
Impaired urea cycle → accumulation of glutamate.
3. Hyperammonemia
Ammonia accumulation increases conversion to glutamate and glutamine.
4. Neurologic Disorders
Some cases of:
- Epilepsy
- Traumatic brain injury
- Neurodegeneration
have altered glutamate levels.
5. Dietary Supplementation
Excessive intake (e.g., monosodium glutamate) rarely causes clinically measurable plasma elevation.
Low Glutamic Acid
- Severe malnutrition
- Vitamin B6 (pyridoxine) deficiency
- Chronic liver failure
- Impaired transamination activity
- Some mitochondrial diseases
Reference Intervals
(Tietz 8E + Mayo + ARUP + IEM guidelines)
Plasma Glutamate
- 20 – 80 µmol/L (adults)
- Higher in newborns: 40–120 µmol/L
- CSF glutamate: Much lower and tightly regulated
Critical Values
- >200 µmol/L → strongly suggest metabolic disorder or severe hepatic dysfunction
- <10 µmol/L → rare; suggests malnutrition or transamination defects
Diagnostic Uses
1. Inborn Errors of Metabolism
Essential in the workup of:
- Urea cycle disorders
- Hyperinsulinism-hyperammonemia syndrome
- Organic acidemias
- Pyridoxine-dependent epilepsy
Often measured alongside:
- Glutamine
- Ammonia
- Alanine
- Citrulline
- Ornithine
2. Liver Function & Hyperammonemia
Elevations correlate with:
- Hepatic encephalopathy
- Ammonia toxicity
3. Nutrition Assessment
Part of amino acid profile in malnutrition or parenteral nutrition monitoring.
4. Neurological Research
(Glutamate measured in plasma or CSF for research; limited clinical application.)
Analytical Notes
- Use fasting plasma (EDTA or heparin)
- Sample must be kept on ice immediately
- Deproteinization required to prevent post-collection metabolism
- Not reliable in serum (platelet release)
- Amino acid analysis by HPLC or tandem mass spectrometry
Clinical Pearls
- Plasma glutamate is a marker of nitrogen load and urea cycle stress.
- High glutamate with high ammonia → think urea cycle defect.
- In neonates, elevated glutamate + seizures → consider pyridoxine-dependent epilepsy.
- Glutamine:glutamate ratio often more informative than glutamate alone.
- Liver disease increases both glutamate and glutamine due to impaired detoxification.
Interesting Fact
Glutamate is the most abundant excitatory neurotransmitter in the human brain, yet high plasma levels do not necessarily reflect CNS levels due to tight blood-brain barrier control.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Amino Acids.
- ACMG Guidelines - Inborn Errors of Metabolism.
- Mayo Clinic Laboratories - Amino Acid Profile.
- ARUP Consult - Urea Cycle Disorders.
- NIH Genetics - Glutamate Metabolism.
- MedlinePlus / NIH - Amino Acid Testing.