STIMULATION OF TUMOR-CELL RESPIRATION BY INHIBITORS OF PYRUVATE-KINASE

STIMULATION OF TUMOR-CELL RESPIRATION BY INHIBITORS OF PYRUVATE-KINASE
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DOI:
10.1111/j.1432-1033.1975.tb02165.x
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发表时间:
1975-01-01
期刊:
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子:
--
通讯作者:
WEINHOUSE, S
WEINHOUSE, S
中科院分区:
其他
文献类型:
--
作者:
GOSALVEZ, M;LOPEZALARCON, L;WEINHOUSE, S

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In a model system consisting of highly coupled rat liver mitochondria respiring in the presence of substrate, pyruvate kinase, phosphoenolpyruvate, ATP, hexokinase and glucose, the increase in the mitochondrial concentration results in a progressive decrease in the activity of pyruvate kinase. These results are in accord with a role of pyruvate kinase as a determinant of glycolytic activity by competing with mitochondrial oxidative phosphorylation for the available ADP.The addition of adequate amounts of the amino acids, cysteine, alanine and phenylalanine, known as inhibitors of pyruvate kinase, to living Ehrlich ascites tumor cell suspensions results in a stimulation of the respiratory rate and in a decrease of the glycolytic rate of the cells. Concomitant with these changes, there is an accumulation of intracellular phosphoenolpyruvate and ADP, and a decrease in pyruvate kinase as another key enzyme whose properties and activities may be major determinants for the control of glycolysis and the Crabtree and Pasteur effects of tumor cells.