Plomp P J, Boon L, Caro L H, van Woekom G M, Meijer A J
E. C. Slater Institute for Biochemical Research, University of Amsterdam, The Netherlands.
Eur J Biochem. 1990 Jul 20;191(1):237-43. doi: 10.1111/j.1432-1033.1990.tb19115.x.
Katz et al. [Katz, J., Golden, S. & Wals, P.A. (1976) Proc. Natl Acad. Sci. USA 73, 3433-3437] were the first to report that in hepatocytes isolated from fasted rats and incubated with either dihydroxyacetone, glucose or other sugars, glycogen synthesis was greatly accelerated by addition of amino acids. We have looked for possible mediators responsible for this effect and have tested the effect of alanine, proline, asparagine, glutamine or a combination of ammonia with either pyruvate or lactate in activating glycogen synthesis from dihydroxyacetone. The following observations were made. 1. Stimulation of glycogen synthesis by alanine, proline or asparagine does not require production of glutamine since the effect also occurs in periportal hepatocytes which lack glutamine synthetase. 2. Under various conditions, stimulation of glycogen synthesis by added amino acids directly correlated with increases in the intracellular content of amino acids, expressed in osmotic equivalents. 3. 3-Mercaptopicolinic acid, the inhibitor of phosphoenolpyruvate carboxykinase, further enhances stimulation of glycogen synthesis by amino acids because it increases the intracellular accumulation of aspartate and glutamate. 4. The previously reported enhancement by leucine of the stimulation of glycogen synthesis by glutamine [Chen. K. S. & Lardy, H. A. (1985) J. Biol. Chem. 260, 14683-14688] can be ascribed to inhibition of urea synthesis by leucine which results in accumulation of glutamate and of ammonia, the essential activator of glutaminase. It is concluded that activation of glycogen synthesis by added amino acids is due to an increase in intracellular osmolarity following their uptake and the accumulation of intracellular catabolites. This results in an increase in hepatic volume which stimulates glycogen synthesis [Baquet, A., Hue, L., Meijer, A. J., van Woerkom, G. M. & Plomp, P. J. A. M. (1990) J. Biol. Chem. 265, 955-959].
卡茨等人[卡茨，J.，戈尔登，S.和瓦尔兹，P.A.（1976年）《美国国家科学院院刊》73卷，3433 - 3437页]最先报道，在从禁食大鼠分离出的肝细胞中，用二羟基丙酮、葡萄糖或其他糖类进行孵育时，添加氨基酸可极大地加速糖原合成。我们已寻找了可能介导这种效应的物质，并测试了丙氨酸、脯氨酸、天冬酰胺、谷氨酰胺或氨与丙酮酸或乳酸的组合对从二羟基丙酮激活糖原合成的作用。得出了以下观察结果。1. 丙氨酸、脯氨酸或天冬酰胺对糖原合成的刺激并不需要谷氨酰胺的生成，因为在缺乏谷氨酰胺合成酶的门静脉周围肝细胞中也会出现这种效应。2. 在各种条件下，添加氨基酸对糖原合成的刺激与以渗透当量表示的细胞内氨基酸含量的增加直接相关。3. 磷酸烯醇式丙酮酸羧激酶的抑制剂3 - 巯基吡啶甲酸可进一步增强氨基酸对糖原合成的刺激，因为它增加了天冬氨酸和谷氨酸在细胞内的积累。4. 先前报道的亮氨酸对谷氨酰胺刺激糖原合成的增强作用[陈，K.S.和拉迪，H.A.（1985年）《生物化学杂志》260卷，14683 - 14688页]可归因于亮氨酸对尿素合成的抑制，这导致谷氨酸和氨（谷氨酰胺酶的必需激活剂）的积累。得出的结论是，添加氨基酸对糖原合成的激活是由于它们被摄取后细胞内渗透压的增加以及细胞内分解代谢产物的积累。这导致肝脏体积增大，从而刺激糖原合成[巴凯，A.，于埃，L.，梅杰，A.J.，范·沃科姆，G.M.和普洛姆，P.J.A.M.（1990年）《生物化学杂志》265卷，955 - 959页]。
