Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de Barcelona, Joan XXIII s/n, 08028 Barcelona, Spain.
Br J Nutr. 2012 Jun;107(12):1747-56. doi: 10.1017/S000711451100496X. Epub 2011 Sep 30.
In liver, through the reaction catalysed by alanine aminotransferase (ALT), alanine becomes an effective precursor for gluconeogenesis. In the present study amino-oxyacetate (AOA) was used to evaluate its effect on liver ALT activity of the carnivorous fish Sparus aurata. Moreover, the derived metabolic effects on metabolites and other key enzymes of glycolysis, gluconeogenesis and the pentose phosphate pathway were also studied. A dose-effect-dependent inhibition of AOA on hepatic cytosolic and mitochondrial ALT activity was observed in vitro. In vivo, AOA behaved as an inhibitor of hepatic cytosolic ALT activity. A long-term exposure to AOA increased pyruvate kinase activity in the liver irrespective of the composition of the diet supplied to fish. 1H NMR studies showed that inclusion of AOA to the diet decreased the hepatic levels of alanine, glutamate and glycogen. Moreover, 2H NMR analysis indicated a higher renewal rate for alanine in the liver of fish fed with a high-carbohydrate/low-protein diet, while AOA decreased alanine 2H-enrichment irrespective of the diet. The present study indicates that AOA-dependent inhibition of the cytosolic ALT activity could help to increase the use of dietary carbohydrate nutrients.
在肝脏中，通过丙氨酸氨基转移酶（ALT）催化的反应，丙氨酸成为糖异生的有效前体。本研究使用氨基氧乙酸（AOA）来评估其对肉食性鱼类真鲷肝脏 ALT 活性的影响。此外，还研究了由此产生的对糖酵解、糖异生和磷酸戊糖途径的代谢物和其他关键酶的影响。在体外观察到 AOA 对肝胞质和线粒体 ALT 活性具有剂量依赖性抑制作用。在体内，AOA 表现为肝胞质 ALT 活性的抑制剂。长期暴露于 AOA 会增加肝脏中丙酮酸激酶的活性，而不论所供应的饮食中组成如何。1H NMR 研究表明，在饮食中添加 AOA 会降低肝脏中丙氨酸、谷氨酸和糖原的水平。此外，2H NMR 分析表明，在高碳水化合物/低蛋白质饮食喂养的鱼的肝脏中，丙氨酸的更新率更高，而 AOA 则降低了丙氨酸的 2H 富集，而与饮食无关。本研究表明，AOA 依赖性抑制胞质 ALT 活性有助于增加膳食碳水化合物营养物质的利用。
