PATHWAYS OF ADENINE NUCLEOTIDE CATABOLISM IN HUMAN ERYTHROCYTES: 20

Abstract

Adenine nucleotide catabolism in erythrocytes incubated for 4h under physiological conditions is very low as shown by a production of hypoxanthine (HX) of 4.2 ± 0.7 nmol/h per g of packed cells (mean ± SEM for n=8). It is not influenced by maximal inhibition of adenosine (Ado) deaminase by 10 μM deoxycoformycin (dCF) and of Ado-kinase by 10 μM iodotubercidin (ITu) indicating that it proceeds by deamination of AMP, followed by dephosphorylation of IMP, and that there is no recycling between AMP and Ado. Suppression of glucose increases AMP 30-fold and the production of HX 20-fold. dCF decreases this production by 75 % and provokes an accumulation of Ado, demonstrating a dephosphorylation of AMP. ITu enhances this accumulation, indicating a recycling of Ado under glucose deprivation which reaches approx. 20 nmol/h per ml of cells. Alcalinisation of the incubation medium in the presence of glucose increases AMP 5-fold and the production of HX 15-fold. dCF has no effect on this production, demonstrating that it results from a deamination of AMP. ITu also evidences recycling of Ado under this condition, reaching 25 nmol/h per ml of cells. The 2-fold elevation of intracellular Pi during glucose deprivation and its 50 % decrease during alcalinisation, as well as experiments in which extracellular Pi was modified, indicate that the dephosphorylation of AMP is mainly responsive to variations of AMP, whereas its deamination is more sensitive to modifications of Pi.Supported by FRSM.