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The Interconversion of Lactate and Pyruvate and Its Effect on the Apparent Oxidative Decarboxylation of These Substrates in Normal Tissue and Ascites Tumor Cells¹

The Department of Experimental Medicine and Cancer Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel

The interconversion of lactate and pyruvate and its effect on the apparent oxidative decarboxylation of these substrates in Landschuetz ascites tumor cells and in normal rat kidney slices has been studied. This reaction, which apparently proceeds by the mediation of lactate dehydrogenase and DPN according to the equation CH₂·CHOH·COOH¹⁴C + CH₂·CO·COOH CH₂·CO·COOH¹⁴C + CH₂·CHOH·COOH when one of the substrates used is labeled, is readily demonstrable in both these tissues, even under aerobic conditions.

The rate of interconversion in the actively respiring kidney slices was at least as high as the oxidative decarboxylation of the substrates. It proceeded more rapidly in the tumor cells in which its rate was 4–5 times as high as that of the oxidative decarboxylation.

The failure of pyruvate to suppress the radioactive CO₂-production from lactate-1-¹⁴C was observed only in the tumor cells, and only when these were present in excess with regard to the equilibration of the isotopic carbon. This phenomenon has been attributed to the rapid interconversion and high degree of equilibration of the radioactive carbon between the 2 substrates, obtained prior to their oxidative decarboxylation.

Pyruvate markedly inhibited the disappearance of lactate in the kidney slices and arrested it completely in the case of the tumor cells even when it failed to suppress the apparent ¹⁴CO₂ production from the carboxyl-labeled substrate.

These results suggest that the isotopic CO₂ produced by the tumor cells from lactate-1-¹⁴C in the presence of an equimolar concentration of pyruvate is derived entirely via the interconversion of these substrates. They further suggest that the radioactive CO₂ production from lactate-1-¹⁴C is not a valid criterion for the ability of the mammalian cells to consume and oxidize this substrate, since it may result from the interconversion of the latter with endogenously generated pyruvate.

¹ This investigation was supported by Research Grant CA-05271 of the National Cancer Institute, NIH, USPHS.

² Part of this study will be included in a thesis to be presented by Dalia Ram to the Hebrew University, in partial fulfillment of the requirements of the Ph.D. degree.

Received 9/23/65. Revised 3/ 2/66.