Rémésy C, Moundras C, Morand C, Demigné C
Laboratoire des Maladies Métaboliques et des Micronutriments, InstitutNational de la Recherche Agronomique de Clermont-Ferrand/Theix, Saint-Genès-Champanelle, France.
Am J Physiol. 1997 Feb;272(2 Pt 1):G257-64. doi: 10.1152/ajpgi.1997.272.2.G257.
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.
本研究的目的是探究当饮食中蛋白质缺乏时肝脏对氮的 salvage 机制。为此，将大鼠分别适应于轻度缺乏（11%酪蛋白）或中度过量（22%酪蛋白）的饮食蛋白质水平。在餐后或吸收后阶段对动物进行采样，并测定其消化道和肝脏的通量。在吸收后阶段，两个饮食组的消化道谷氨酰胺均呈负平衡。在餐后阶段，尽管膳食中谷氨酰胺和谷氨酸供应充足，但谷氨酰胺的消化平衡仍为负，这表明在此期间谷氨酰胺的利用率最高。两个饮食组的肝脏均有谷氨酸和谷氨酰胺的净生成，但低蛋白饮食喂养的大鼠谷氨酰胺释放量高73%。在这些动物中，由于尿素生成能力相对较低，氮的利用转向谷氨酰胺合成：肝脏对氨基酸的总体摄取约为5.3微摩尔/分钟，谷氨酰胺+谷氨酸的净释放约为2.9微摩尔/分钟（因此，以摩尔为基础，循环率为55%）。在适应22%酪蛋白饮食的大鼠中，这种循环率仅为12%。当考虑肝脏氨摄取时，氮循环呈现平行变化：适应11%或22%酪蛋白饮食的大鼠分别为64%或15%。除了谷氨酰胺输送外，肝脏还释放谷氨酸，为肝外组织提供氮源。在蛋白质缺乏饮食的情况下，肝脏谷氨酰胺输送主要用于满足肠道代谢的底物需求，这是一种氮 salvage 机制。氮代谢从尿素向谷氨酰胺生成的这种转变可能意味着谷氨酸从门静脉周围向合成谷氨酰胺的肝静脉周围肝细胞转移。
