PATHWAY OF GLUTAMINE AND GLUTAMATE OXIDATION IN ISOLATED MITOCHONDRIA FROM MAMMALIAN CELLS
PATHWAY OF GLUTAMINE AND GLUTAMATE OXIDATION IN ISOLATED MITOCHONDRIA FROM MAMMALIAN CELLS
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DOI：
10.1042/bj1250757
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发表时间：
1971-01-01
影响因子：
4.1
通讯作者：
KOVACEVIC, Z
中科院分区：
文献类型：
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作者：
KOVACEVIC, Z
1. 在谷氨酰胺或谷氨酸存在的情况下，丙酮酸强烈抑制从艾利希腹水肿瘤细胞中分离的线粒体以及大鼠肾和肝呼吸的天冬氨酸产生；尽管1-[U-14C]谷氨酸被抑制50%以上，但1-[U-14C]谷氨酰胺生成14CO2并未受到抑制。 2.在葡萄糖存在下，完整的艾氏腹水肿瘤细胞在谷氨酰胺氧化过程中天冬氨酸产生的抑制并不伴随着CO 2 产生的抑制。 3.添加氨基氧乙酸几乎完全抑制天冬氨酸的产生，但在谷氨酰胺存在下不抑制线粒体的呼吸，尽管在谷氨酸存在下线粒体的呼吸受到抑制。 4.谷氨酸在谷氨酰胺存在下刺激肾线粒体的呼吸，但天冬氨酸的产生与单独谷氨酸存在时相同。 5. 结果表明，如果转氨途径受到抑制，则线粒体谷氨酰胺酶活性产生的谷氨酸氧化几乎可以完全通过谷氨酸脱氢酶途径进行。这表明谷氨酸的氧化不受高[NADPH]/[NADP+]比率的限制。 6. 有人认为，在生理条件下，与谷氨酸脱氢酶途径相比，转氨途径是艾利希腹水肿瘤细胞（或许还有肾脏）中谷氨酸（由谷氨酰胺水解产生）氧化的不太有利的途径，因为乙酰辅酶A的产生强烈抑制第一种机制。转氨途径在分离线粒体氧化谷氨酸中占主导地位，可以通过线粒体内膜对谷氨酸的通透性受限以及谷氨酸-草酰乙酸转氨酶比谷氨酸脱氢酶更有利的位置来解释。
1. Pyruvate strongly inhibited aspartate production by mitochondria isolated from Ehrlich ascites-tumour cells, and rat kidney and liver respiring in the presence of glutamine or glutamate; the production of14CO2froml-[U-14C]glutamine was not inhibited though that froml-[U-14C]glutamate was inhibited by more than 50%. 2. Inhibition of aspartate production during glutamine oxidation by intact Ehrlich ascites-tumour cells in the presence of glucose was not accompanied by inhibition of CO2production. 3. The addition of amino-oxyacetate, which almost completely suppressed aspartate production, did not inhibit the respiration of the mitochondria in the presence of glutamine, though the respiration in the presence of glutamate was inhibited. 4. Glutamate stimulated the respiration of kidney mitochondria in the presence of glutamine, but the production of aspartate was the same as that in the presence of glutamate alone. 5. The results suggest that the oxidation of glutamate produced by the activity of mitochondrial glutaminase can proceed almost completely through the glutamate dehydrogenase pathway if the transamination pathway is inhibited. This indicates that the oxidation of glutamate is not limited by a high [NADPH]/[NADP+] ratio. 6. It is suggested that under physiological conditions the transamination pathway is a less favourable route for the oxidation of glutamate (produced by hydrolysis of glutamine) in Ehrlich ascites-tumour cells, and perhaps also kidney, than the glutamate dehydrogenase pathway, as the production of acetyl-CoA strongly inhibits the first mechanism. The predominance of the transamination pathway in the oxidation of glutamate by isolated mitochondria can be explained by a restricted permeability of the inner mitochondrial membrane to glutamate and by a more favourable location of glutamate–oxaloacetate transaminase compared with that of glutamate dehydrogenase.