Erythrocyte disorders of purine and pyrimidine metabolism.
The maturing reticulocyte degrades ribosomal RNA to constituent ribonucleoside phosphates. Guanosine ribonucleotides are retained only in small amounts and pyrimidine ribonucleotides only in trace quantities. In the mature erythrocyte more than 97% of total nucleotides are the interconvertible adenosine mono-, di-, and triphosphates. High energy ATP fuels most of the reactions required to sustain viability. Unable to synthesize adenosine phosphates from small precursor molecules, the red cell relies on certain salvage pathways to replenish its losses from the adenosine phosphate pool. The most important of these involve adenosine. Adenylate kinase deficiency, when severe, is associated with nonspherocytic hemolytic anemia. A genetically-determined deficiency of pyrimidine 5'-nucleotidase prevents the normal dephosphorylation of pyrimidine ribonucleotides, and hence is characterized by the unique accumulation of pyrimidine phosphates intracellularly. Other features are chronic hemolytic anemia, splenomegaly, and a profound increase in basophilic stippling on the stained blood film. The syndrome is transmitted as an autosomal recessive disorder. A similar syndrome is found in severe lead poisoning as a consequence of nucleotidase inhibition by lead. An inherited, dominantly transmitted hemolytic anemia associated with low red cell ATP and a 45-70 fold increase in the enzymatic activity of adenosine deaminase has also been documented. The undefined molecular lesion appears to involve overproduction of an entirely normal enzyme protein. Severe deficiency of either of two sequential enzymes of purine metabolism, adenosine deaminase anemia, but by excessive accumulations of deoxyribonucleotides within red cells and lymphocytes. The clinical counterpart of each is a severe immunodeficiency state secondary to lymphopenia and lymphocyte dysfunction. Certain other rare clinical syndromes involving disturbed nucleotide metabolism also are detectable by red cell assay procedures.
D015720:5'-Nucleotidase; D000227:Adenine Nucleotides / Q000097:blood; D000243:Adenosine Deaminase / Q000097:blood; D000263:Adenylate Kinase / Q000172:deficiency; D000743:Anemia, Hemolytic / Q000201:enzymology; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007855:Lead Poisoning / Q000097:blood; D009708:Nucleotidases / Q000172:deficiency; D011683:Purine-Nucleoside Phosphorylase / Q000097:blood / Q000172:deficiency; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000097:blood*; D012156:Reticulocytes / Q000378:metabolism
D000227:Adenine Nucleotides; D011683:Purine-Nucleoside Phosphorylase; D000263:Adenylate Kinase; D009708:Nucleotidases; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase