5 replies to this topic

[ta5]

J Phys Chem B. 2014 Mar 6;118(9):2316-30.

Mechanistic study of the deamidation reaction of glutamine: a computational approach.

Halim MA1, Almatarneh MH, Poirier RA.

Department of Chemistry, Memorial University , St. John's, NL, Canada A1B 3X7.

Glutamine--a popular nutritional supplement, non-toxic amino acid, and an essential interorgan and intercellular ammonia transporter--can destroy the neurons' mitochondria. When glutamine enters (like a Trojan horse) into the mitochondria, in the presence of glutaminase, it reacts with water and yields glutamate and excess ammonia which opens gates in the membrane of the mitochondria and thereby destroys it. The mechanistic details underlying the molecular basis of the catabolic production of excess ammonia remain unclear. In the present paper, both 5-oxoproline-mediated and direct pathways for glutamine deamidation are studied using wave function and density functional theories. The mechanisms are studied both in the gas phase and in aqueous solution using the polarizable continuum model (PCM) and solvent model on density (SMD) solvation models. Among three glutamine deamidation pathways, a two-step pathway, GDB, shows the lowest gas phase barrier height of 189 kJ/mol with the G3MP2B3 level of theory. Incorporation of solvent through PCM and SMD models reduces the barrier height to 183 and 174 kJ/mol, respectively. For the hydrolysis of 5-oxoproline, a two-step mechanism, pathway PH-B, provides a lower gas phase energy barrier (187 kJ/mol) compared to one-step (201 kJ/mol) and three-step (227 kJ/mol) pathways at G3MP2B3. Although direct hydrolysis with OH(-), pathway DHE, has the lowest gas phase barrier of 135 kJ/mol, the solvent has little effect on the barrier. For the direct hydrolysis with OH(-)/H2O, pathway DHF, the overall barrier is 143 kJ/mol, in the gas phase at G3MP2B3. In aqueous solution, the overall barrier decreases to 76 and 75 kJ/mol with PCM and SMD, respectively, at B3LYP/6-31+G(d,p), making this the most plausible mechanism. Compared to PCM, SMD predicts lower barriers for nearly all pathways investigated.

PMID: 24499522

 

 

There are several studies that mention glutamine and Trojan horse, mostly in relation to hepatic encephalopathy. I wonder if there is concern for healthy people taking it.

[zorba990]

-"reacts with water and yields glutamate and excess ammonia "

Interesting, Colgan reccomended using Alpka-Ketoglutarate to avoid the ammonia issue.

[ikon2]

-"reacts with water and yields glutamate and excess ammonia "

Interesting, Colgan reccomended using Alpka-Ketoglutarate to avoid the ammonia issue.

 

I'd like to know more about this.  I like many of Glutamine's actions but had heard something about the Trojan horse stuff and subsequently put it on hold.  Are we confident in GAKG or does it have perils of its own?

Edited by ikon2, 17 November 2014 - 09:43 PM.

[Vastmandana]

wow!  thanks for the post...

[medicineman]

this is in-vitro meaningless crap (sorry for that, not intended at the OP, just the implication of the test tube study)

glutamine is HIGHLY HIGHLY regulated in the CNS. you will never have excess or too little. here is a study of intravenous glutamine in brain injury.

Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury.

Of note:

High dose L-alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction