Bastos M T, Oliveria M B, Campello A P, Klüppel M L
Departamento de Bioquímica da Universidade Federal do Paraná, Brasil.
Cell Biochem Funct. 1990 Oct;8(4):199-203. doi: 10.1002/cbf.290080403.
The effect of methotrexate (MTX) on the mitochondrial oxidation of cytosolic-reducing equivalents in HeLa cells was studied. MTX inhibited (100 per cent) malate dehydrogenase activity, but no effect was observed on that of GOT. MTX (0.5 mM) inhibited (100 per cent) the activity of reconstituted enzymatic system MDH-GOT, probably as a consequence of inhibition of malate dehydrogenase activity. MTX decreased pyruvate production (54 per cent), demonstrating its inhibitory action on the malate-aspartate shuttle. Blockage of the malate-aspartate shuttle by MTX accounts for the decrease in cellular energetic gain. The results obtained are consistent with the view that in HeLa cells, as well as in other tumour cells, the transport of reducing equivalents from cytoplasmic NADH into the respiratory chain of mitochondria is via the malate-aspartate shuttle.
研究了甲氨蝶呤（MTX）对HeLa细胞胞质还原当量线粒体氧化的影响。MTX抑制（100%）苹果酸脱氢酶活性，但对谷草转氨酶活性未观察到影响。MTX（0.5 mM）抑制（100%）重组酶系统MDH - GOT的活性，这可能是抑制苹果酸脱氢酶活性的结果。MTX使丙酮酸生成减少（54%），表明其对苹果酸 - 天冬氨酸穿梭有抑制作用。MTX对苹果酸 - 天冬氨酸穿梭的阻断导致细胞能量获取减少。所得结果与以下观点一致：在HeLa细胞以及其他肿瘤细胞中，还原当量从细胞质NADH转运到线粒体呼吸链是通过苹果酸 - 天冬氨酸穿梭进行的。
