Evidence that the Severity of Depletion of Inorganic Phosphate Determines the Severity of the Disturbance of Adenine Nucleotide Metabolism in the Liver and Renal Cortex of the Fructose-Loaded Rat

A C T To test the hypothesis that in both the liver and renal cortex ofthe fructose-loaded rat, severity of depletion of inorganic phosphate (Pi), and not the magnitude of accumulation of fructose-l-phosphate (F-1-P), determines the severity of the dose-dependent reduction of ATP, we intraperitoneally injected fed rats with fructose, 20 and 40 umol/g, alone, and at the higher load, in combination with (a) sodium phosphate, 20 umol/g, administered shortly beforehand or sub- sequently or, (b) adenosine, 2 ,umol/g, administered beforehand. The following observations were made: (a) With fructose loading alone, at the higher load, both Pi and total adenine nucleotides (TAN) were reduced by one third in the renal cortex and (as previously ob- served) by two thirds in the liver; and at either load, the reduction of ATP (and TAN) and the accumulation of F-I-P were less severe in the renal cortex than in the liver. (b) Prior phosphate loading largely prevented the reductions of ATP and TAN in the renal cortex and significantly attenuated them in the liver, yet doubled the renal cortical accumulation of F-1-P. (c) Adenosine loading substantially attenuated the reductions ofATP, TAN, and Pi only in the renal cortex. (d) ATP varied directly with Pi (P < 0.001, r = 0.98) in the domain of control and reduced values of Pi taken from both liver and renal cortex. (e) As judged from tissue and plasma concentrations of fructose and glucose, and tis- sue concentrations of fructose-6-phosphate and glu- cose-6-phosphate, the rate at which the renal cortex and liver converted fructose to glucose was much lower at the higher fructose load. (f) Prior phosphate loading prevented this decrease in rate in the renal cortex and attenuated it in the liver; adenosine loading attenuated