A study of the citric acid cycle in certain tumour tissue

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Abstract
Utilization of acetate, malate, and/or succinate by way of the citric acid cycle was less in the Walker, LC-18 and mouse ascites tumors than in muscle, liver (homogenates and isolated intact cells) or nucleated erythrocytes. Addition of ATP and 2 concentrations of diphosphopyridine nucleotide to the incubation mixture in the presence of Fl- or triethyltin acetate did not result in any appreciable increase in the amounts of C14-activities of the citric acid-cycle intermediates in tumors. Likewise, fortifying the incubation mixture with either co-enzyme A or preformed acetyl-coenzyme A failed to produce a significant increase in the quantities and activities of the cycle acids. The only increase was in the lipid and acetoacetate fractions. This was considered to indicate that there was no apparent impairment in the activating-enzyme system or excessive loss of ATP or diphosphopyridine nucleotide in the tumors employed. The cycle intermediates, succinate and malate, were not utilized any better by the tumor tissues than was acetate. In view of the above findings, it is concluded that the lowered activity of the cycle in the tumor studied is primarily due to some defect in an intra-Krebs-cycle reaction(s).