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Metabolism of Ascites Tumor Cells

IV. Enzymatic Reactions Involved in Adenosinetriphosphate Degradation Induced by 2-Deoxyglucose^*

R. B. McComb and W. D. Yushok

( Division of Cancer Biochemistry, Biochemical Research Foundation, Newark, Delaware)

The changes in cellular nucleotides accompanying the phosphorylation of 2-deoxyglucose by respiring Krebs ascites tumor cells have been studied. The degradation of ATP by dephosphorylation and deamination to form ADP, AMP, IMP, and inosine in 2-deoxyglucose-treated cells was followed chromatographically and electrophoretically. A rise in cellular AMP concentration, a rise and subsequent fall in cellular IMP, and a steady rise in inosine until it was the predominant 250- to 260-mµ absorbing compound in the reaction mixture were observed when ascites cells were treated with 2-deoxyglucose. GTP was also broken down in 2-deoxyglucose-treated cells, and one of its breakdown products GDP was identified.

A pathway is proposed for the 2-deoxyglucose-induced ATP degradation in these cells. Hexokinase, adenylate kinase, adenylic deaminase, and 5'-nucleotidase, the enzymes necessary for operation of this pathway, were assayed in fractionated or crude homogenates of ascites cells, and their activities were found to be adequate to account for the observed nucleotide changes in the ATP degradation series.

^* This work has been supported in part by Public Health Service research grant C-5118 from the National Cancer Institute.

Present address: Biochemical Research Laboratory, Hartford Hospital, Hartford 15, Connecticut.

Received 3/ 6/63.

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