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.
Rémésy
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Laboratoire des Maladies Métaboliques et des Micronutriments, InstitutNational de la Recherche Agronomique de Clermont-Ferrand/Theix, Saint-Genès-Champanelle, France.
Moundras
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Morand
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Demigné
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D000042:Absorption; D000818:Animals; D002244:Carbon / Q000378:metabolism; D004435:Eating; D018698:Glutamic Acid / Q000097:blood / Q000378:metabolism*; D005973:Glutamine / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009584:Nitrogen / Q000378:metabolism*; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D014781:Viscera / Q000378:metabolism
D005973:Glutamine; D018698:Glutamic Acid; D002244:Carbon; D009584:Nitrogen