Effects of Decreased Glutamine Supply on Gut and Liver Metabolism in vivo in Rats

Abstract

1. It has recently been suggested that glutamine may be a conditionally essential nutrient rather than a non-essential amino acid. Therefore, administration of methionine sulphoximine was used to create a model of decreased arterial glutamine concentrations for 4 days. Glutamine consumption in portal-drained viscera and liver was measured after an overnight fast by determining fluxes and intracellular concentrations in normal rats, methionine sulphoximine-treated rats and pair-fed controls. Moreover, fluxes and intracellular concentrations of several other amino acids and ammonia and production of urea by the liver were determined concomitantly. 2. Methionine sulphoximine treatment for 4 days resulted in a 50% decrease in arterial glutamine concentration. Although the glutamine consumption and the intracellular glutamine concentration of the intestine were reduced by 50% at day 4, no changes in intestinal amino acid and ammonia metabolism were observed. 3. In the liver, glutamine consumption was reduced and ammonia uptake was increased, but urea synthesis was not changed. The decreased intracellular glutamine, glutamate, aspartate and ammonia concentrations coincided with a substantial reduction in liver branched-chain amino acid production. 4. These results suggest that reduced intestinal glutamine uptake does not induce marked changes in intestinal amino acid metabolism. The decreased liver branched-chain amino acid production suggests a reduction in the net liver protein degradation rate during methionine sulphoximine treatment.