Glutamine or glutamate release by the liver constitutes a major mechanism for nitrogen salvage

The aim of the present study was to investigate mechanisms of N salvage by the liver when a diet is protein deficient. For this purpose, rats were adapted to a slightly deficient (11% casein) or moderately surfeit (22% casein) dietary protein level. Animals were sampled during the postprandial or the postabsorptive period, and fluxes across the digestive tract and liver were determined. During the postabsorptive period there was a negative balance of glutamine across the digestive tract in both diet groups. During the postprandial period the digestive balance of glutamine was still negative, despite a substantial supply of dietary glutamine and glutamate, suggesting that glutamine utilization is maximal during this period. There was a net production of glutamate and glutamine by the liver in both diet groups, but glutamine release was 73% higher in rats fed the low-protein diet. In these animals, because of the relatively low capacity of ureagenesis, N utilization was shifted toward glutamine synthesis: overall uptake of amino acids by the liver was approximately 5.3 micromol/min, and net release of glutamine + glutamate was approximately 2.9 micromol/min (hence a 55% cycling, on a molar basis). This cycling was only 12% in rats adapted to the 22% casein diet. When liver ammonia uptake was taken into account, N cycling showed parallel changes: 64% or 15% in rats adapted to the 11% or 22% casein diet, respectively. Besides glutamine delivery, glutamate was also released by the liver, representing an N source for extrasplanchnic tissues. With protein-deficient diets, hepatic glutamine delivery mainly serves to fulfill substrate needs for intestinal metabolism, which represents a mechanism for N salvage. This shift of N metabolism from urea toward glutamine production may imply a glutamate transfer from periportal to glutamine-synthesizing perivenous hepatocytes.