THE USE OF GLUTAMINE IN THE TREATMENT OF GASTROINTESTINAL DISORDERS IN MAN

The human gastrointestinal tract (GIT) is a major site of glutamine ut ilisation accounting for more than half of the net splanchnic utilisat ion (similar to 15 g/day) of glutamine obtained from the systemic circ ulation. Dietary glutamine (similar to 5 g/day) is less important than circulating glutamine, especially in disease conditions associated wi th substantial reduction in food intake. Glutamine has multiple effect s on the structure and function of the GIT, and effects in improving m orbidity and mortality in animal models of GIT damage has led to a ser ies of studies in man, which have produced variable results. Glutamine administration to treat mucositis of the upper GIT (mouth, oesophagus ) due to cytotoxic drug therapy, has produced no evidence of benefit. Early studies suggested improved healing, as do recent studies of smal l intestinal mucositis resulting from chemotherapy. Investigations in colitis are lacking although in experimental rat models of colitis, no benefit has been reported. Multiple explanations can be put forward t o explain the overall results, including the GIT distribution of enzym es involved in glutamine metabolism. Apart from the lower stomach in m an (upper stomach in the rat) there is very little weak activity of gl utamine synthetase, suggesting that the gut derives glutamine formed i n other tissues and from the diet. The activity of glutaminase, which is key flux generating enzyme involved in glutaminolysis is very weak in mucosa with stratified squamous epithelium (oesophagus), where inte rmediate in the same intestine, and highest in the small intestinal mu cosa which accounts for about 80% of the total glutaminase in the enti re human GIT mucosa. (C)Elsevier Science Inc. 1997.