Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0398564 (Adenylate kinase deficiency)
 3 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Erythrocyte disorders of purine and pyrimidine metabolism. 625 19

Abnormalities in erythrocyte nucleotide metabolism are associated with hereditary nonspherocytic hemolytic anemia. Deficiency of adenylate kinase and pyrimidine 5'-nucleotidase and hyperactivity of adenosine deaminase shorten the red cell lifespan. Deficiency of adenylate kinase has been reported in four different families. Although in one family, total absence of this enzymatic activity was documented in one hematologically normal sibling, there is doubt about the capacity of this single enzyme deficiency to produce hemolysis. A deficiency of pyrimidine 5'-nucleotidase is a cause of hemolytic anemia characterized by red cells with basophilic stippling. This enzyme has been reported to catalyze the hydrolytic dephosphorylation of pyrimidine 5'-ribose monophosphate. Red cells of patients contain an increased concentration of pyrimidine nucleotides and reduced form of glutathione. In hyperactivity, the adenosine deaminase activity in erythrocytes may be increased to 100 times the normal level. The high adenosine deaminase activity of erythrocytes depletes adenine nucleotides, inhibiting its metabolism.
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PMID:[Hemolytic anemia due to abnormalities in erythrocyte nucleotide metabolism]. 889 May 81