Optimal Result: 0.06 - 0.23 Ratio.

The Glutamic Acid/Glutamine Ratio is used to identify specimen handling issues that cause spontaneous degradation of glutamine to glutamate, and can reveal the origin of difficulty maintaining systemic pH balance.

What is Glutamate (glutamic acid)?

Glutamate is the major excitatory neurotransmitter in the brain which is necessary for memory and learning. In fact, it is believed that 70% of the fast excitatory central nervous system synapses utilize glutamate as a transmitter.

An event or process that dramatically increases the activity of glutamate often induces the death of neurons. Such a scenario is believed to take place in e.g. ischemia, trauma, hypoxia, hypoglycemia, and hepatic encephalopathy.; More mild but chronic malfunctioning of glutamatergic systems may be involved in many neurodegenerative diseases such as Huntington’s disease, Parkinson’s disease, Alzheimer’s disease, vascular dementia, amyotrophic lateral sclerosis, AIDS-neurodegeneration, Tourette’s syndrome, and Korsakoff syndrome.

It is unlikely that a disturbance of glutamate homeostasis is the sole initiator of these neurodegenerative diseases, but rather that excitotoxicity plays a pivotal executive role in events triggered by other processes such as energy deficits that facilitate the neurotoxic potential of endogenous glutamate.

What is Glutamine?

Glutamine is an amino acid which acts as a precursor to glutamate. Glutamine aids in the maintenance of gut barrier function, intestinal cell proliferation and differentiation. Glutamine supplementation is commonly utilized to help repair the mucosal lining of the gut which can help with food sensitivities and other stomach/ intestinal issues. High levels may be a sign of inhibitory/excitatory imbalances in the neurotransmitter system.

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References:

https://pubmed.ncbi.nlm.nih.gov/16776830/
https://pubmed.ncbi.nlm.nih.gov/32236804/
https://ur.booksc.eu/book/26508184/4fffe8
https://pubmed.ncbi.nlm.nih.gov/11844641/
https://pubmed.ncbi.nlm.nih.gov/9755377/
https://pubmed.ncbi.nlm.nih.gov/429309/
https://www.epilepsybehavior.com/article/S1525-5050(13)00327-2/fulltext
https://academic.microsoft.com/paper/2952506610/citedby/search?q=High%20plasma%20glutamate%20and%20low%20glutamine-to-glutamate%20ratio%20are%20associated%20with%20type%202%20diabetes%3A%20Case-cohort%20study%20within%20the%20PREDIMED%20trial&qe=RId%253D2952506610&f=&orderBy=0
https://www.uv.es/symbiosis/pdfs/palomo-buitragoetal2019.pdf
https://abran.org.br/new/wp-content/uploads/2021/05/1617646504_glutamato_glutamina_ic.pdf
https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00561/full
https://www.sciencedirect.com/science/article/abs/pii/S0197018606003299?via%3Dihub
https://pubmed.ncbi.nlm.nih.gov/8841951/

What does it mean if your Glutamic Acid/Glutamine result is too low?

High protein intake may contribute to higher levels of Glutamine and hence a lower Glutamic Acid/Glutamine ratio. It should also be noted that glutamine is available as a nutraceutical supplement. Elevations of Glutamine can also be seen with supplementation.

The metabolism of glutamine requires several cofactors, such as NADPH and vitamin B1. Functional deficiencies of vitamin and mineral cofactors can also elevate Glutamine levels. There is literature to suggest vitamin B1 supplementation lowers elevated levels of glutamine, as well as other amino acids in thiamine deficiency. 

Because of the relationship of glutamine and glutamate to both the Cahill Cycle and Urea Cycle, elevations of glutamine are associated with hyperammonemia due to increased production of glutamine from glutamate.

Another reason for a lower Glutamic Acid/Glutamine ratio is a low level of Glutamic acid. Low protein intake, GI malabsorption, and maldigestion can all contribute to low levels of amino acids. As above, there are many endogenous pathways which create glutamate, each with vitamin and mineral cofactors. Lack of those cofactors should also be considered. No specific symptomatology has been attributed to low glutamic acid levels.

What does it mean if your Glutamic Acid/Glutamine result is too high?

- Increased ratio of glutamate/glutamine to creatine in the right hippocampus contributes to depressive symptoms in patients with epilepsy
- High plasma glutamate and high glutamate to glutamine ratio are associated with type 2 diabetes
- High plasma glutamate and high glutamate to glutamine ratio are associated with increased risk of heart failure
- Dysfunction in the glutamate-glutamine cycle could contribute to excitotoxicity mediated by glutamate.
- Low plasma glutamine in combination with high glutamate levels indicate risk for loss of body cell mass in healthy individuals.
- Low plasma glutamine, and high venous glutamate levels are common among patients with cancer or human immunodeficiency virus infection.

Glutamate plays a role in apoptosis induction and oxidative stress, whereas glutamine plays a role in myocardial metabolism and exerts potent antioxidant and anti-inflammatory effects in the circulation by inducing the expression of heme oxygenase-1, heat shock proteins, and glutathione. Both of them are also involved in energy metabolism.


 

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