Pathways of adenine nucleotide catabolism in erythrocytes.

Abstract

The exact pathway whereby the initial catabolism of the adenine nucleotides proceeds from AMP and the possibility of a recycling of adenosine were investigated in human erythrocytes. Adenine nucleotide catabolism, reflected by the production of hypoxan- thine, is very slow under physiologic conditions and can be greatly increased by suppression of glucose or alkalinization of the me- dium. Experiments with inhibitors of adenosine deaminase and adenosine kinase demonstrated that under physiologic conditions the initial catabolism of AMP proceeds by way of a deamination of AMP, followed by dephosphorylation of inosine monophos- phate, and that no recycling occurs between AMP and adenosine. Under glucose deprivation, -75% of the 20-fold increase of the catabolism of the adenine nucleotides proceeded by way of a dephosphorylation of AMP followed by deamination of adeno- sine, and a small recycling of this nucleoside could be evidenced. Inhibition of adenosine transport showed that the dephosphor- ylation of AMP occurred intracellularly. When the incubation medium was alkalinized in the presence of glucose, the 15-fold increase in the conversion of AMP to hypoxanthine proceeded exclusively by way of AMP deaminase but a small recycling of adenosine could also be evidenced. The threefold elevation of intraerythrocytic inorganic phosphate (PI) during glucose depri- vation and its 50% decrease during alkalinization as well as ex- periments in which extracellular P1 was modified, indicate that the dephosphorylation of red blood cell AMP is mainly respon- sive to variations of AMP, whereas its deamination is more sen- sitive to Pi.