In many types of tumor cells, this interlocking coordination appears to be defective: glycolysis proceeds at a higher rate than required by the citric acid cycle. As a result, cancer cells use far more blood glucose than normal cells, but cannot oxidize the excess pyruvate formed by rapid glycolysis, even in the presence of O2. To reoxidize cytoplasmic NADH, most of the pyruvate is reduced to lactate (Chapter 14), which passes from the cells into the blood. The high glycolytic rate may result in part from smaller numbers of mitochondria in tumor cells. In addition, some tumor cells overproduce an isozyme of hexokinase that associates with the cytosolic face of the mitochondrial inner membrane and is insensitive to feedback inhibition by glucose-6phosphate (p. 432). This enzyme may monopolize the ATP produced in mitochondria, using it to produce glucose-6-phosphate and committing the cell to continue glycolysis.
Lehninger-Nelson-Cox: Principles of Biochemistry, 568.o.
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