Adenosine 3':5'-cyclic monophosphate (cAMP)-inducible pyrimidine 5'-nucleotidase and pyrimidine nucleotide metabolism of chick embryonic erythrocytes.
Terminally differentiating erythrocytes degrade most of their RNA with subsequent release of mononucleotides. Pyrimidine mononucleotides are preferentially cleaved by an erythrocyte-specific pyrimidine 5'-nucleotidase; deficiency of this enzyme causes hemolytic anemia in humans. Details of the regulation of its activity during erythroid differentiation are unknown. The present study arose from the observation that the immature red blood cells (RBCs) of mid-term chick embryos contain high concentrations of uridine 5'-triphosphate (UTP) (5 to 6 mmol/L), which decline rapidly from days 13 to 14 onward. We analyzed two key enzymes of RBC pyrimidine nucleotide metabolism: pyrimidine nucleoside phosphorylase (PNP) and pyrimidine 5'-nucleotidase (P-5'-N), to evaluate if changes of enzyme activity during embryonic development are correlated with changes of RBC UTP. Secondly, we tested if these enzymes are under hormonal control. The results show that embryonic RBCs contain only minimal activity of PNP. In contrast, P-5'-N increases from day 13 on, suggesting that the enzyme is a limiting factor in UTP degradation. Activation of beta-adrenergic and A2A-adenosine receptors causes transcription-dependent de novo synthesis of P-5'-N. Because beta-adrenergic and adenosine receptors are also found on adult erythroid cells, P-5'-N might be an enzyme of differentiating RBCs whose expression is in part controlled by adenosine 3':5'-cyclic monophosphate (cAMP).
Dragon
S
S
Physiologisches Institut, Universität Regensburg, Regensburg, Germany.
Hille
R
R
Götz
R
R
Baumann
R
R
D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D011743:Pyrimidines / Q000378:metabolism*
D011743:Pyrimidines; D000242:Cyclic AMP; D015720:5'-Nucleotidase; C030986:pyrimidine