HIGH AEROBIC GLYCOLYSIS OF RAT HEPATOMA-CELLS IN CULTURE - ROLE OF MITOCHONDRIAL HEXOKINASE - (L-LACTIC ACID-D-GLUCOSE-D-GALACTOSE-LIVER-NEOPLASIA)
HIGH AEROBIC GLYCOLYSIS OF RAT HEPATOMA-CELLS IN CULTURE - ROLE OF MITOCHONDRIAL HEXOKINASE - (L-LACTIC ACID-D-GLUCOSE-D-GALACTOSE-LIVER-NEOPLASIA)
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DOI：
10.1073/pnas.74.9.3735
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发表时间：
1977-01-01
影响因子：
11.1
通讯作者：
PEDERSEN, PL
中科院分区：
文献类型：
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作者：
BUSTAMANTE, E;PEDERSEN, PL
在偶氮染料诱导的大鼠腹水肝癌培养中建立了致瘤性锚定依赖细胞系H-91。当在含葡萄糖的培养基中生长时，细胞表现出快速生长的肿瘤细胞特征的高乳酸生成率。当葡萄糖被半乳糖取代时，细胞生长得同样好，但乳酸的产生率只有适度提高。这种观察的分子基础不能归因于渗透性的差异，因为葡萄糖和半乳糖进入肝癌细胞的初始速率是相同的。相反，肝癌细胞中己糖激酶（ATP: d -己糖6-磷酸转移酶，EC 2.7.1.1）的活性较高，约为对照和再生大鼠肝脏的20倍。肿瘤己糖激酶活性不受低浓度（< 0.6 mM）反应产物葡萄糖-6-磷酸的抑制。此外，肝癌细胞50%的己糖激酶活性与线粒体部分有关。该部分的己糖激酶活性比匀浆高3倍，比核和线粒体后部分高4倍。肿瘤线粒体己糖激酶似乎与氧化磷酸化直接耦合，因为向呼吸性肝癌线粒体添加葡萄糖（在ATP合成爆发后）导致呼吸刺激。葡萄糖对来自控制和再生肝脏的线粒体的呼吸没有影响。H-91肝癌细胞的高糖酵解能力至少部分是由于细胞线粒体部分中己糖激酶的升高。
A tumorigenic anchorage-dependent cell line (H-91) was established in culture from an azo-dye-induced rat ascites hepatoma. When grown in a glucose-containing medium the cells exhibit high rates of lactic acid production characteristic of rapidly growing tumor cells. When glucose is replaced with galactose the cells grow equally well but exhibit only moderately elevated rates of lactic acid production. The molecular basis for this observation cannot be attributed to differences in permeability because initial rates of glucose and galactose entry into hepatoma cells are identical. Rather, the activity of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) is high in hepatoma cells, about 20-fold higher than that of control and regenerating rat liver. Tumor hexokinase activity is not inhibited by low concentrations (< 0.6 mM) of the reaction product glucose-6-phosphate. Additionally, 50% of the hexokinase activity of hepatoma cells is associated with the mitochondrial fraction. This fraction is 3-fold enriched in hexokinase activity relative to the homogenate and 4-fold enriched relative to the nuclear and postmitochondrial fractions. Tumor mitochondrial hexokinase appears to be coupled directly to oxidative phosphorylation, because addition of glucose to respiring hepatoma mitochondria (after a burst of ATP synthesis) results in stimulation of respiration. Glucose has no effect on the respiration of mitochondria from control and regenerating liver. The high glycolytic capacity of H-91 hepatoma cells is due, at least in part, to an elevated form of hexokinase concentrated in the mitochondrial fraction of the cell.