Stabilization of adenylate energy charge by the adenylate deaminase reaction
Journal of Biological Chemistry
In the physiological range of the adenylate energy charge in liver (0.7 to 0.9) the rate of deamination of AMP catalyzed by rat liver adenylate deaminase (EC 126.96.36.199) increases sharply with decreasing energy charge. It is suggested that this response serves to protect against sharp transient decreases in energy charge: when the charge decreases the resulting removal of AMP by deamination will oppose the decrease in charge (the mole fraction of ATP plus half the mole fraction of ADP). The
... of ADP). The activity of the enzyme decreases sharply as the size of the adenine nucleotide pool decreases in and below the physiological range. This effect may be a self-limiting response to prevent excessive depletion of the pool. These suggestions, based on the properties of the enzyme observed in vifro, are consistent with the results of experiments on liver in uivo reported by other workers. In liver, as in most other tissues and organisms studied, the adenylate energy charge (the mole fraction of ATP plus half the mole fraction of ADP (1)) has been shown to be maintained at a value of approximately 0.90 (Refs. 2 and 3; compilation in Ref. 4). When liver is subjected to metabolic stress, such as the trapping of large amounts of phosphate that results from the presence of abnormally high levels of a phosphoryl acceptor, a relatively small drop in the energy charge value is accompanied by a decrease in the total concentration of adenine nucleotides (5-8). This is illustrated by a very interesting experiment reported by Raivio el al. (7) , whose results are plotted in Fig. 1 . Rats injected with fructose exhibit a rapid decrease in hepatic adenine nucleotide concentration. Krebs and co-workers (8) obtained similar results using a perfused liver system, and showed that the decrease in the adenine nucleotide level was accompanied by an increase in the concentration of IMP. This result suggests that the decrease in the adenylate pool level may result from the action of adenylate deaminase. If this enzyme were to become active when the charge falls, the resulting removal of AMP would tend to buffer or protect the value of the energy charge (since removal of AMP must increase the mole fractions of ATP and ADP). This protection would be, of course, at the expense of a decrease in the total adenylate pool. The proposed protection requires that the adenylate deaminase reaction go slowly, if at all, under normal physiological conditions, but more rapidly as the charge falls.