HEPATOCYTE HETEROGENEITY IN GLUTAMINE AND AMMONIA METABOLISM AND THE ROLE OF AN INTERCELLULAR GLUTAMINE CYCLE DURING UREOGENESIS IN PERFUSED-RAT-LIVER
HEPATOCYTE HETEROGENEITY IN GLUTAMINE AND AMMONIA METABOLISM AND THE ROLE OF AN INTERCELLULAR GLUTAMINE CYCLE DURING UREOGENESIS IN PERFUSED-RAT-LIVER
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DOI：
10.1111/j.1432-1033.1983.tb07458.x
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发表时间：
1983-01-01
期刊：
影响因子：
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通讯作者：
HAUSSINGER, D
中科院分区：
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作者：
HAUSSINGER, D
短句来源本研究通过比较生理顺行（门静脉到门静脉）和逆行（门静脉到门静脉），研究了离体大鼠肝脏中谷氨酰胺和氨的代谢对灌注方向的依赖性。添加的铵离子在顺行灌注时主要转化为尿素，在逆行灌注时主要转化为谷氨酰胺。在没有添加氨的情况下，内源性产生的铵离子在顺行中转化为谷氨酰胺，但在逆行灌注中被冲走。当蛋氨酸亚砜胺抑制谷氨酰胺合成酶时，灌注方向对添加氨和内源氨合成尿素没有影响。[1‐14C]谷氨酰胺在顺行灌注中的co2产量高于逆行灌注，这是逆行灌注期间标记稀释的结果。在限制氨供应的条件下，谷氨酰胺和尿素合成的底物和酶活性沿肝小叶的梯度解释了这一结果，并且它们与谷氨酰胺合成酶的近静脉定位和谷氨酰胺酶和尿素合成的主要近门静脉定位一致。此外，数据表明内源性氨的产生主要发生在门静脉周围。结果为细胞间（而非细胞内）谷氨酰胺循环及其在不同代谢条件下的作用提供了基础。
1The metabolism of glutamine and ammonia was studied in isolated perfused rat liver in relation to its dependence on the direction of perfusion by comparing the physiological antegrade (portal to caval vein) to the retrograde direction (caval to portal vein).2Added ammonium ions are mainly converted to urea in antegrade and to glutamine in retrograde perfusions. In the absence of added ammonia, endogenously arising ammonium ions are converted to glutamine in antegrade, but are washed out in retrograde perfusions. When glutamine synthetase is inhibited by methionine sulfoximine, direction of perfusion has no effect on urea synthesis from added or endogenous ammonia.314CO2production from [1‐14C]glutamine is higher in antegrade than in retrograde perfusions as a consequence of label dilution during retrograde perfusions.4The results are explained by substrate and enzyme activity gradients along the liver lobule under conditions of limiting ammonia supply for glutamine and urea synthesis, and they are consistent with a perivenous localization of glutamine synthetase and a predominantly periportal localization of glutaminase and urea synthesis. Further, the data indicate a predominantly periportal localization of endogenous ammonia production. The results provide a basis for an intercellular (as opposed to intracellular) glutamine cycling and its role under different metabolic conditions.