de Sagarra M R, Hochuli R, Piquerez R, Anabitarte M, Walter P
Rev Esp Fisiol. 1978 Jun;34(2):177-86.
Previous findings that 2.5 mM quinolinic acid inhibits gluconeogenesis more strongly from alanine than from lactate have been confirmed. 15 mM quinolinic acid completely inhibited gluconeogenesis from lactate as well as from alanine whereas the formation of glucose from fructose and the production of urea from ammonia and lactose were not affected. The pattern of the gluconeogenic intermediates was the same in the presence of 15 mM quinolinic acid as with 2.5 mM of the inhibitor. It is concluded that high as well as low concentrations of quinolinic acid inhibit gluconeogenesis at the step between oxaloacetate and phosphoenolpyruvate. Furthermore, 5-methoxyindole-2-carboxylic acid, an inhibitor of mitochondrial pyruvate metabolism, also completely blocked gluconeogenesis from lactate whereas glycerol conversion to glucose was only weakly inhibited. All these results do not support the concept of an alternate pathway of gluconeogenesis from lactate proposed by others. 2.5 mM quinolinic acid also partially blocked the formation of urea from alanine. It is suggested that quinolinic acid may have a second site of action causing an inhibition of the glutamate-pyruvate transamination owing to lack of 2-oxoglutarate in the cytosol. In the presence of quinolinic acid, glucagon caused about the same increase in aspartate and malate tissue levels in the absence of added substrates as in the presence of added lactate or alanine. Therefore, no additional effect of glucagon on gluconeogenesis from lactate or alanine prior to the block by quinolinic acid could be demonstrated.
先前的研究发现，2.5 mM喹啉酸对从丙氨酸生成葡萄糖的糖异生作用的抑制比从乳酸生成葡萄糖的抑制更强，这一发现得到了证实。15 mM喹啉酸完全抑制了从乳酸以及从丙氨酸的糖异生作用，而从果糖生成葡萄糖以及从氨和乳糖生成尿素的过程则未受影响。在存在15 mM喹啉酸时，糖异生中间产物的模式与存在2.5 mM该抑制剂时相同。得出的结论是，高浓度和低浓度的喹啉酸均在草酰乙酸和磷酸烯醇丙酮酸之间的步骤抑制糖异生作用。此外，线粒体丙酮酸代谢的抑制剂5-甲氧基吲哚-2-羧酸也完全阻断了从乳酸的糖异生作用，而甘油转化为葡萄糖仅受到微弱抑制。所有这些结果均不支持其他人提出的从乳酸进行糖异生的替代途径的概念。2.5 mM喹啉酸也部分阻断了从丙氨酸生成尿素的过程。有人提出，喹啉酸可能有第二个作用位点，由于胞质溶胶中缺乏2-氧代戊二酸而导致谷氨酸-丙酮酸转氨基作用受到抑制。在存在喹啉酸的情况下，胰高血糖素在未添加底物时引起的天冬氨酸和苹果酸组织水平的升高与添加乳酸或丙氨酸时大致相同。因此，在喹啉酸阻断之前，未证明胰高血糖素对从乳酸或丙氨酸进行的糖异生作用有额外影响。
