The role of phosphometabolites in cell proliferation, energy metabolism, and tumor therapy

被引:139
作者
Mazurek, S [1 ]
Boschek, CB [1 ]
Eigenbrodt, E [1 ]
机构
[1] UNIV GIESSEN, FAC MED, INST MED VIROL, GIESSEN, GERMANY
关键词
glycolysis; pyruvate kinase type M-2; glutaminolysis; hydrogen shuttles; phosphometabolites; AMP; NADH; NADPH; apoptosis; tumor therapy;
D O I
10.1023/A:1022490512705
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
A common characteristic of tumor cells is the constant overexpression of glycolytic and glutaminolytic enzymes. In tumor cells the hyperactive hexokinase and the partly inactive pyruvate kinase lead to an expansion of all phosphometabolites from glucose 6-phosphate to phosphoenolpyruvate. In addition to the glycolytic phosphometabolites, synthesis of their metabolic derivatives such as P-ribose-PP, NADH, NADPH, UTP, CTP, and UDP-N-acetyl glucosamine is also enhanced during cell proliferation. Another phosphometabolite derived from P-ribose-PP, AMP, inhibits cell proliferation. The accumulation of AMP inhibits both P-ribose-PP-synthetase and the increase in concentration of phosphometabolites derived from P-ribose-PP. In cells with low glycerol 3-phosphate and malate-aspartate shuttle capacities the inhibition of the lactate dehydrogenase by low NADH levels leads to an inhibition of glycolytic ATP production. Several tumor-therapeutic drugs reduce NAD and NADH levels, thereby inhibiting glycolytic energy production. The role of AMP, NADH, and NADPH levels in the success of chemotherapeutic treatment is discussed.
引用
收藏
页码:315 / 330
页数:16
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