Uncertainties regarding the role of
pyrimidine nucleotidase (PyrNase) in
AMP catabolism were resolved by studies of erythrocytes from normal controls, controls with young mean cell ages, and patients with
hereditary hemolytic anemia due to severe deficiency of PyrNase. Hemolysates from the latter exhibited undiminished capacity to dephosphorylate
AMP over a broad range of pH, indicating that PyrNase was not directly involved. In each subject group, the rates of
AMP dephosphorylation between pH 5.1 and 8.3 were indistinguishable from those of
IMP, suggesting a potential role for
AMP-deaminase, an erythrocyte
enzyme that was stimulated by
coformycin at pH 7.2. Quantitative analysis of catabolites in incubated hemolysates confirmed that
AMP degradation preferentially occurred via deamination to
IMP with subsequent dephosphorylation by another erythrocyte
nucleotidase isozyme, deoxyribonucleotidase. Both
AMP-deaminase and deoxyribonucleotidase have acidic pH optima with minimal activities at physiologic pH, suggesting that this pathway of
AMP catabolism could accelerate depletion of the
adenine nucleotide pool and thereby mediate the demise of senescent erythrocytes sequestered in the spleen.