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Metabolism of Renal Tumors in Situ and during Ischemia¹

External Staff, Medical Research Council, London, [D. H. W.]; England Metabolic Research Laboratory, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, OX2 6HE, [H. A. K., M. S., M. A. P.]; England Department of Biochemistry, Howard University School of Medicine, Washington, D. C. 20001 [H. P. M.]; and Department of Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana 46202 [G. W.]

The concentrations of ATP, ADP, AMP, creatine phosphate, glucose, lactate, pyruvate, glucose 6-phosphate, glycerol 3-phosphate, malate, glutamate, 2-oxoglutarate, acetoacetate, and 3-hydroxybutyrate have been measured in freeze-clamped Renal Tumors 8997-K (MK-1) and 9789-K (MK-3). Samples were taken within 5 sec after excision of the tumor and during the subsequent ischemia up to 10 min. The results were compared with similar values for liver and kidney. The activities of enzymes responsible for the initial stages of the catabolism of free fatty acids and ketone bodies (acyl-CoA synthetase, 3-oxo acid-CoA transferase, acetoacetyl-CoA thiolase, and 3-hydroxybutyrate dehydrogenase) were also measured in order to evaluate the relative importance of these potential fuels of respiration.

In contrast to kidney and liver, the renal tumors maintained their ATP levels during ischemia provided that glycolysis occurred. After inhibition of glycolysis by iodoacetamide, ATP was no longer maintained.

The rates of glycolysis during ischemia, as measured by lactate production, were 6- to 8-fold higher in the tumors than in kidney. The glucose 6-phosphate decreased in both tumors by about 50% during ischemia. More lactate was formed than glucose removed in both tumors and kidneys. The lactate/pyruvate and glutamate/oxoglutarate ratios increased during ischemia, whereas there was no change in the 3-hydroxybutyrate/acetoacetate ratio. The activity of 3-hydroxybutyrate dehydrogenase in the tumors was hardly measurable and was probably insufficient to establish equilibrium between its substrates. Ischemia did not alter the glycerol 3-phosphate concentration appreciably.

The activities of acyl-CoA synthetase, 3-oxo acid-CoA transferase, and acetoacetyl-CoA thiolase in the tumors indicate that free fatty acids and acetoacetate can act as fuels of respiration.

¹ This work was supported in part by the Medical Research Council, London, and by USPHS Grant AM 11748.

² Supported by USPHS Grant CA-10729.

³ Supported in part by USPHS Grant CA-05034 and American Cancer Society and Damon Runyon Memorial Fund grants.

Received 2/10/70. Accepted 4/ 1/70.