Regeneration Nucleotide pools

The accumulation of fructose 1-phosphate also substantially depletes the phosphate pools. The fructokinase reaction uses ATP at a rapid rate such that the mitochondria regenerate ATP rapidly, which leads to a drop in free phosphate levels. The low levels of phosphate release inhibition of AMP deaminase, which converts AMP to inosine monophosphate (IMP). The nitrogenous base of IMP (hypoxanthine) is degraded to uric acid. The lack of phosphate and depletion of adenine nucleotides lead to a loss of ATP, further contributing to the inhibition of biosynthetic pathways, including gluconeogenesis. 

In experiments of this type with animal tissues, Rose and Schweigert (2) and Thomson et al. (S) showed that pyrimidine ribonucleosides were converted to DNA nucleotides without cleavage of the JNT-glycosidic bond. As well, Larsson and Neilands (4) performed a similar type of experiment in which P-phosphate and uniformly labeled C-cytidine were administered to rats with regenerating liver. Both substances were incorporated into the liver polynucleotides which, upon isolation, were degraded to their constituent nucleotides for analysis. Their data (Table 16-1) showed that the four nucleotides of RNA had similar specific activities with respect to P, indicating that the labeled phosphate readily equilibrated with the nucleoside phosphate pool during the experimental period. In this experiment, cytidylate derived from RNA and deoxycytidylate derived from DNA had the same P C ratio. This result indicated that both polynucleotide subunits, deoxycytidylate and cytidylate, were derived from a common precursor, evidently a ribonucleotide. 

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