The pathway of AMP catabolism and its control in isolated rat hepatocytes subjected to anoxia.

Abstract

In anoxic conditions, the hepatic concentrations of high energy phosphates, most notably ATP, decrease to a marked extent, whereas those of AMP and Pi increase several-fold (Deuticke and Gerlach, 1966; Busch et al., 1968; Hems and Brosnan, 1970; Jackson et al., 1976). The exact pathway of the further catabolism of AMP in this situation has been a subject of controversy: whereas Deuticke and Gerlach (1966) have proposed that the initial degradation of AMP occurs by way of AMP deaminase and is followed by the dephosphorylation of IMP by 5′-nucleotidase, Busch et al. (1968) have asserted that the degradation of AMP involves a prior dephosphorylation by the same enzyme, followed by deamination of adenosine by adenosine deaminase. The present study was undertaken with isolated rat hepatocytes in order to try to solve this controversy. As in our previous work, coformycin was used to determine the pathway of degradation of AMP. In the liver, this inosine analog inhibits selectively adenosine deaminase at concentrations around 0.1 μM, whereas at concentrations around 50 μM, it also inhibits AMP deaminase (Van den Berghe et al., 1980). If the initial degradation of AMP occurs by way of 5′-nucleotidase, the low concentration of coformycin would decrease the formation of the terminal products of adenine nucleotide catabolism. If, however, the initial step of the degradation of AMP is catalyzed by AMP deaminase, the decrease in the production of purine catabolites would be observed only at high concentrations of coformycin. Further details concerning the experiments reported and a description of the methodology can be found in Vincent et al. (1982).