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 salvag e by the liver when a diet is protein deficient. For this purpose, rat s were adapted to a slightly deficient (11% casein) or moderately surf eit (22% casein) dietary protein level. Animals were sampled during th e postprandial or the postabsorptive period, and fluxes across the dig estive tract and liver were determined. During the postabsorptive peri od there was a negative balance of glutamine across the digestive trac t in both diet groups. During the postprandial period the digestive ba lance of glutamine was still negative, despite a substantial supply of dietary glutamine and glutamate, suggesting that glutamine utilizatio n is maximal during this period. There was a net production of glutama te and glutamine by the liver in both diet groups, but glutamine relea se was 73% higher in rats fed the low-protein diet. In these animals, because of the relatively low capacity of ureagenesis, N utilization w as shifted toward glutamine synthesis: overall uptake of amino acids b y the liver was similar to 5.3 mu mol/min, and net release of glutamin e + glutamate was similar to 2.9 pmol/min (hence a 55% cycling, on a m olar basis). This cycling was only 12% in rats adapted to the 22% case in diet. When liver ammonia uptake was taken into account, N cycling s howed parallel changes: 64% or 15% in rats adapted to the 11% or 22% c asein diet, respectively. Besides glutamine delivery, glutamate was al so released by the liver, representing an N source for extrasplanchnic tissues. With protein-deficient diets, hepatic glutamine delivery mai nly 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.