Glutamine and the bowel

Since the pioneering work of Windmueller and Spaeth, the importance of glut amine to the support of intestinal mucosal metabolic function has become ge nerally accepted. Nevertheless, the mechanisms underlying this role still r emain obscure. This paper explores a number of questions: 1) Is glutamine e ssential for intestinal function? 2) To what extent does this relate to its intermediary metabolism? 3) What is the importance of glutamine as a biosy nthetic precursor? 4) Is glutamine supplementation of the nutrient mixture presented to patients of any metabolic or clinical benefit? As a result of this exploratory exercise, the following general conclusions were reached: 1) Much suggestive biochemical and physiologic evidence exists that implies that glutamine, especially systemic glutamine, supports the function of th e intestinal mucosal system. 2) Despite the extensive metabolism of this am ino acid by the intestinal tissues, most evidence suggests that if glutamin e does play a physiologic role in the bowel, it is not compellingly related to its intermediary metabolism. 3) There is, on the other hand, evidence t hat the mucosal cells not only utilize extracellular glutamine but synthesi ze the amino acid. Given that inhibition of glutamine synthesis inhibits bo th proliferation and differentiation of mucosal cell cultures, this suggest s some more subtle regulatory role. This notion is supported by the demonst ration that glutamine will activate a number of genes associated with cell cycle progression in the mucosa. 4) Despite the accumulated evidence, the m echanisms underlying glutamine's function and the question whether glutamin e supplementation uniformly benefits mucosal health remain equivocal at bes t.