A novel synergistic effect of alanosine and guanine on adenine nucleotide synthesis in mammalian cells. Alanosine as a useful probe for investigating purine nucleotide metabolism

A 6-mercaptopurine (6-MP)-resistant subline of the Ehrlich ascites carcinoma developed in this laboratory has been reported previously to lack the ability to synthesize thioinosinate, a characteristic believed to be related to mercaptopurine resistance. A comparison was made of various aspects of purine nucleotide metabolism in cells of the parent tumor line and the resistant subline in order to detect differences which, if they existed, might account for resistance to 6-MP.The synthesis of adenylate or of inosinate from adenine-8-C14was found to take place at similar rates in the two cell types under conditions in which adenylate renewal was independent of adenine-8-C14concentration. Both cell types synthesized adenylate and inosinate at comparable rates from hypoxanthine-8-C14and had equivalent adenylate deaminase activities. The size of the pool of inosinate in the tumor cells was measured by the isotope dilution method and that of the Ehrlich cells was found to be 1.6 times the pool size of the resistant cells. The conversion of guanine-8-C14to guanylate took place at similar rates in both tumors.In general, no differences in purine nucleotide metabolism were revealed which were obviously related to resistance or to the characteristic inability of the resistant subline to synthesize thioinosinate. This inability did not appear to be due to an inadequacy of the phosphoribosylpyrophosphate resources of the resistant cell, since the rates of purine nucleotide synthesis were similar in the two cell types. In Part II it is shown that extracts of the 6-MP-resistant cells catalyzed the synthesis of thioinosinate. It was concluded that the failure of intact resistant cells to synthesize thioinosinate was due to failure of 6-MP to enter the cell.

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Purine Nucleotide Metabolism in Mammalian Cells

Biochemical Society Transactions ◽

10.1042/bst0031195 ◽

1975 ◽

Vol 3 (6) ◽

pp. 1195-1198 ◽

Cited By ~ 4

Author(s):

J. FRANK HENDERSON

Keyword(s):

Mammalian Cells ◽

Nucleotide Metabolism ◽

Purine Nucleotide ◽

Purine Nucleotide Metabolism

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Influence of sprint training on human skeletal muscle purine nucleotide metabolism

Journal of Applied Physiology ◽

10.1152/jappl.1994.76.4.1802 ◽

1994 ◽

Vol 76 (4) ◽

pp. 1802-1809 ◽

Cited By ~ 109

Author(s):

C. G. Stathis ◽

M. A. Febbraio ◽

M. F. Carey ◽

R. J. Snow

Keyword(s):

Skeletal Muscle ◽

Human Skeletal Muscle ◽

Adenine Nucleotide ◽

Cycle Ergometer ◽

Nucleotide Metabolism ◽

Atp Depletion ◽

Purine Nucleotide ◽

Sprint Training ◽

Similar Reduction ◽

Purine Nucleotide Metabolism

To examine the effect of sprint training on human skeletal muscle purine nucleotide metabolism, eight active untrained subjects completed a maximal 30-s sprint bout on a cycle ergometer before and after 7 wk of sprint training. Resting muscle ATP and total adenine nucleotide content were reduced (P < 0.05) by 19 and 18%, respectively, after training. Training resulted in a 52% attenuation (P < 0.05) in the magnitude of ATP depletion after exercise and a similar reduction (P < 0.05) in the accumulation of inosine 5′-monophosphate and ammonia. During recovery, muscle inosine 5′-monophosphate (P < 0.05) and inosine (P < 0.01) content were reduced after training, as was the accumulation of inosine (P < 0.05). Plasma ammonia was higher (P < 0.05) after training early in recovery; in contrast, plasma hypoxanthine concentrations were reduced (P < 0.05) during the latter stages of recovery. The attenuated resting ATP and total adenine nucleotide contents after training probably result from the acute effects of prior training sessions. The reduction in the magnitude of ATP depletion during a 30-s sprint bout after training must reflect an improved balance between ATP hydrolysis and resynthesis. It is unclear which mechanism(s) is responsible for the reduction in the magnitude of ATP degradation after training.

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RESISTANCE TO 6-MERCAPTOPURINE: I. BIOCHEMICAL DIFFERENCES BETWEEN THE EHRLICH ASCITES CARCINOMA AND A 6-MERCAPTOPURINE-RESISTANT SUBLINE

Canadian Journal of Biochemistry and Physiology ◽

10.1139/o62-023 ◽

1962 ◽

Vol 40 (2) ◽

pp. 181-194 ◽

Cited By ~ 12

Author(s):

A. R. P. Paterson ◽

A. Hori

Keyword(s):

Ehrlich Ascites Carcinoma ◽

Cell Types ◽

Nucleotide Metabolism ◽

Isotope Dilution Method ◽

Dilution Method ◽

Purine Nucleotide ◽

Nucleotide Synthesis ◽

Ehrlich Ascites ◽

Purine Nucleotide Metabolism ◽

Resistant Cells

A 6-mercaptopurine (6-MP)-resistant subline of the Ehrlich ascites carcinoma developed in this laboratory has been reported previously to lack the ability to synthesize thioinosinate, a characteristic believed to be related to mercaptopurine resistance. A comparison was made of various aspects of purine nucleotide metabolism in cells of the parent tumor line and the resistant subline in order to detect differences which, if they existed, might account for resistance to 6-MP.The synthesis of adenylate or of inosinate from adenine-8-C14was found to take place at similar rates in the two cell types under conditions in which adenylate renewal was independent of adenine-8-C14concentration. Both cell types synthesized adenylate and inosinate at comparable rates from hypoxanthine-8-C14and had equivalent adenylate deaminase activities. The size of the pool of inosinate in the tumor cells was measured by the isotope dilution method and that of the Ehrlich cells was found to be 1.6 times the pool size of the resistant cells. The conversion of guanine-8-C14to guanylate took place at similar rates in both tumors.In general, no differences in purine nucleotide metabolism were revealed which were obviously related to resistance or to the characteristic inability of the resistant subline to synthesize thioinosinate. This inability did not appear to be due to an inadequacy of the phosphoribosylpyrophosphate resources of the resistant cell, since the rates of purine nucleotide synthesis were similar in the two cell types. In Part II it is shown that extracts of the 6-MP-resistant cells catalyzed the synthesis of thioinosinate. It was concluded that the failure of intact resistant cells to synthesize thioinosinate was due to failure of 6-MP to enter the cell.

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