Low Solubility and Kinetics of Spontaneous Degradation of L-Glutamine in Aqueous Solution

The authors of this article [Arii et al., 1999a: (http://www.ncbi.nlm.nih.gov/pubmed/10493999)] cite research showing that L-glutamine degrades spontaneously to 5-pyrrolidone-2-carboxylic acid, at a rate of between 0.7 and 5 percent per day, in aqueous solution at pH values near 7 (neutral, as in the pH of tap water, etc.). The authors' own experiments show that, at 70 degrees C (158 degrees F), about 50 percent of the glutamine is gone in about 12 hours, at pH 7.39. That's a high temperature and would presumably accelerate the reaction rate, but it's still much slower than the degradation of the pyruvate anion in aqueous solution. Arii et al. (1999a) mention old research showing that glutamine can degrade to glutamic acid and ammonia in aqueous solution, and I remember reading some statements, by relatively unreliable sources, implying that this degradation was really rapid. It's not rapid, and the information in this article is consistent with information in other, reliable articles I've seen. The main reason free glutamine isn't commonly used in solutions for parenteral administration is that its solubility is quite low, but it's not as low as one might think. It just can't be used in "highly concentrated" solutions. I have an article that discusses this. Researchers primarily administer glutamine in the form of L-alanyl-L-glutamine, a dipeptide. In terms of its long-term "shelf life," that dipeptide is obviously much more stable than glutamine [Arii et al., 1999b: (http://www.ncbi.nlm.nih.gov/pubmed/9845788)]. I don't think that would substantially confound attempts to make subjective interpretations of data collected in people receiving intravenous glutamine, in the form of that dipeptide. The export of alanine from the skeletal muscles tends to coincide with the output of glutamine from the skeletal muscles (in vivo) [Cersosimo et al., 1986: (http://www.ncbi.nlm.nih.gov/pubmed/3513612)], and the metabolism of orally-administered glutamine by intestinal epithelial cells sometimes produces an elevation of plasma alanine, etc.