Mechanistic Study of the Deamidation Reaction of Glutamine: A Computational Approach
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".