Coordination of adenylate energy charge and phosphorylation state during ischemia and under physiological conditions in rat liver and kidney

Abstract

The relation of the adenylate energy charge ( ATP + 1 2 ADP/ATP + ADP + AMP) to the phosphorylation state (ATP)/(ADP)(HPO 4 2−) in rat liver and kidney was analyzed. Under physiological conditions and in ischemia, the two regulatory parameters, calculated from reported values for adenine nucleotides and inorganic phosphate (P i) and from new observations, were closely coordinated. Energy charge was an inverse linear function of P i and -log (1 - energy charge) was a positive linear function of log phosphorylation state. To evaluate experimental data with known energy charge, but unknown P i, and to determine the theoretical relation between energy charge and phosphorylation state, P i was estimated from a) the regression equation: P i , μmol/g wet wt tissue = 1.05 - energy charge/0.073 and b) the empirical relationship: (P i/2P a) + energy charge = k, where P a = σAMP + 2ADP + 3ATP and k = 1. With both estimates, the relation between phosphorylation state and energy charge for the experimental data was, within error, the same as that observed with measured P i and concordant with theoretical values. Over the physiological range of energy charge (∼0.85 – 0.95, log phosphorylation state ∼3.3 – 4.3), apparent ΔG ATP (×2) was closer to the range of ΔG observed by Wilson et al (Biochem. J. 140 :57, 1974) for transfer of two electrons from mitochondrial NAD to the cytochrome c couple than the ΔG ATP (×2) they reported, supporting their conclusion that near-equilibrium exists between the mitochondrial respiratory chain and the cytoplasmic phosphorylation state under physiological conditions. From evidence presented, it is postulated that the phosphorylation state is regulated by the adenylate energy charge.