The production of pyruvic acid, oxaloacetic acid and α-oxoglutaric acid from glucose by tissue in culture

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Abstract
Monolayers of chick-embryo mesenchyma tissue and of human tumor tissue (HeLa) were incubated for 24 hr. with radioactive glucose. When the supply of glucose per cell is raised, the ratio of radioactive lactic acid to radioactive CO2 accumulated increases sharply, indicating a shift from respiration to fermentation. In stationary conditions, the quantities of the 3 keto acids can be calculated from their radioactivities. These quantities are small and correspond to the lactic acid or CO2 generated during a few minutes only. The average amount of each keto acid within a cell increases parallel with the supply of glucose, but the ratio of the 3 keto acids does not change appreciably. Thus the enzymes of the citric acid cycle can, to a large extent, cope with an increase in the supply of pyruvic acid. Pyruvic acid diffuses, from both mesenchyma and tumor tissue, into the medium where it is acted upon by lactic dehydrogenase. In the given conditions, the inverse Pasteur effect can partly be explained as being due to this reaction. Oxaloacetic acid and a-oxoglutaric acid diffuse into the medium from tumor, but not from mesenchyma tissue. This loss is attributed to some malfunction of the mitochondria in tumor tissue. But it is shown that this malfunction need not express itself in any great increase of the ratio of pyruvic acid to oxaloacetic acid or [alpha]-oxoglutaric acid within the cells or any great decrease in the rate of respiration.