A SIMPLE-MODEL FOR ALANINE METABOLISM IN ISOLATED RAT HEPATOCYTES
A SIMPLE-MODEL FOR ALANINE METABOLISM IN ISOLATED RAT HEPATOCYTES
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DOI：
10.1016/0167-4889(93)90019-l
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发表时间：
1993-01-17
期刊：
影响因子：
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通讯作者：
BAVEREL, G
中科院分区：
文献类型：
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作者：
MARTIN, G;VINCENT, N;BAVEREL, G
本文提出了一种描述空腹大鼠肝细胞中丙氨酸代谢反应的简单模型，并将其应用于以L-[1-C-14]-、L-[2-C-14]-、L-[3-C-14]-和L-[U-C-14]丙氨酸以及L-丙氨酸+ (NaHCO3)- c -14为平行底物的放射性实验数据。通过测量标签与葡萄糖和CO2结合的速率，以及所使用的不同底物中[1-C-14]丙酮酸、[1-C-14]乳酸、[1-C-14]丙氨酸和[1-C-14]谷氨酸加[1-C-14]谷氨酰胺的积累速率，可以计算模型中考虑的各种代谢步骤中丙氨酸碳的通量。[1-C-14]丙氨酸释放的(CO2)-C-14的计算值与实测值吻合，以及用两种不同方法计算的丙酮酸羧化酶通量值吻合，表明了该模型的有效性。结果表明，丙酮酸羧化酶合成的草酰乙酸进入Krebs循环和磷酸烯醇丙酮酸合成途径的比例大致相等，丙氨酸代谢合成的草酰乙酸约有40%来自Krebs循环操作。这些结果，加上丙氨酸碳通过丙酮酸脱氢酶的通量可以忽略不计的结论，与已知的禁食状态下肝脏丙氨酸代谢特征一致，因此为本研究提出的模型的有效性提供了进一步的证据。
A simple model describing reactions of alanine metabolism in isolated hepatocytes from fasted rats is proposed and applied to radioactive data obtained in experiments in which L-[ 1-C-14]-, L-[2-C-14]-, L-[3-C-14]-, and L-[U-C-14]alanine as well as L-alanine plus (NaHCO3)-C-14 were used as substrates in parallel. Measurements of the rates of incorporation of the label into glucose and CO2 and of accumulation of [1-C-14]pyruvate, [1-C-14]lactate, [1-C-14]alanine and [1-C-14]glutamate plus [1-C-14]glutamine from the different substrates used allows to calculate flux of alanine carbon through the various metabolic steps taken into account in the model. The validity of this model is indicated by the agreement found between calculations and measurement of the (CO2)-C-14 released from [1-C-14]alanine as well as between the values of flux through pyruvate carboxylase calculated in two different ways. It is shown that the oxaloacetate synthesized by pyruvate carboxylase enters into the Krebs cycle and into the pathway of phosphoenolpyruvate synthesis in about equal proportions and that about 40% of the oxaloacetate synthesized as a result of alanine metabolism is derived from the Krebs cycle operation. These results, together with the conclusion that flux of alanine carbon through pyruvate dehydrogenase is negligible, are in agreement with known characteristics of hepatic alanine metabolism in the fasted state and, therefore, provide further evidence for the validity of the model proposed in the present study.