Pathways of adenine nucleotide catabolism in erythrocytes.
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 hypoxanthine, is very slow under physiologic conditions and can be greatly increased by suppression of glucose or alkalinization of the medium. 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 monophosphate, and that no recycling occurs between AMP and adenosine. Under glucose deprivation, approximately 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 adenosine, and a small recycling of this nucleoside could be evidenced. Inhibition of adenosine transport showed that the dephosphorylation 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 deprivation and its 50% decrease during alkalinization as well as experiments in which extracellular Pi was modified, indicate that the dephosphorylation of red blood cell AMP is mainly responsive to variations of AMP, whereas its deamination is more sensitive to Pi.
D000227:Adenine Nucleotides / Q000097:blood*; D000241:Adenosine / Q000097:blood; D001639:Bicarbonates / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D004163:Diphosphoglyceric Acids / Q000097:blood; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D010710:Phosphates / Q000097:blood; D010879:Piperazines / Q000494:pharmacology
D000227:Adenine Nucleotides; D001639:Bicarbonates; D001786:Blood Glucose; D004163:Diphosphoglyceric Acids; D010710:Phosphates; D010879:Piperazines; C041518:mioflazine; D000241:Adenosine