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Aerobic Glycolysis in Homogenates of Normal and Tumor Tissues^*

( McArdle Memorial Laboratory, Medical School, University of Wisconsin, Madison, Wis.)

1. A system for the aerobic glycolysis of HDP by tissue homogenates has been developed.

2. A grading of oxidative capacity from high values for normal tissues to low values for tumor tissues has been observed in this system. Brilliant cresyl blue doubled the oxygen uptake of three out of four tumor tissues, while no effect was observed with four normal tissues. These data are interpreted in terms of a limited capacity of the DPN-cytochrome c reductase in tumor tissues.

3. Measurements of lactic acid production and phosphate breakdown were used to study the effect of inhibitors and substrates on the aerobic glycolysis of normal and tumor tissues. Lactic acid production with HDP as substrate in the fluoride-inhibited system was similar with normal and tumor tissues. Quantitative data on the action of fluoride in stimulating oxygen uptake and inhibiting both lactic acid formation and phosphate breakdown were obtained. Addition of antimycin A or omission of cytochrome c reduced the oxygen uptake and phosphate breakdown in some tissues but had essentially no effect on lactic acid production.

4. With the probable exception of brain, which was not studied, a clear-cut difference in the capacity to produce lactic acid from glucose was observed between homogenates of normal and tumor tissues. Brain homogenates carry out this reaction anaerobically. The other normal tissues were unable to produce lactic acid from glucose in the absence of other substrates, while neoplastic tissues produced considerable quantities of lactic acid under identical conditions. However, addition of HDP stimulated the production of lactic acid from glucose in heart and kidney. These data confirm previous findings by LePage for anaerobic glycolysis.

^* A preliminary report has been given (14).

Received 7/15/53.

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