Pyrimidine Hypoxanthine guanine phosphoribosyl

In many cells, the capacity for de novo synthesis to supply purines and pyrimidines is insufficient, and the salvage pathway is essential for adequate nucleotide synthesis. In patients with Lesch-Nyhan disease, an enzyme for purine salvage (hypoxanthine guanine phosphoribosyl pyrophosphate transferase, HPRT) is absent. People with this genetic deficiency have CNS deterioration, mental retardation, and spastic cerebral palsy associated with compulsive self-mutilation, Cells in the basal ganglia of the brain (fine motor control) normally have very high HPRT activity. These patients also all have hyperuricemia because purines cannot be salvaged. 

The patient s RBC ADA activity was 43 000 nmol.min . ml RBC " (normal values 495 i 60), There was an about 3-fold increase of red cell pyrimidine 5 -nucleotidase and orotate phosphoribosyl-transferase, whereas other enzymes of purine and pyrimidine metabolism (inosine phosphorylase, adenosine kinase, adenine phosphoribo-syltransferase, hypoxanthine-guanine-phosphoribosyltransferase, phosphoribosylpyrophosphate synthetase) were normal or slightly elevated. There was a 6-fold increase of pyruvate kinase activity relatively to comparably reticulocyte-rich blood, and a 1.5 to 3-fold increase of the other enzymatic activities of glucose and glutathione metabolism. Plasma ADA was much elevated (30.5 pmol.min . ml normal value 5.1 - 2.5), probably reflecting intravascular hemolysis. ADA activity in lymphocytes (2.13 nmol.min 1.10 cells normal 1.93 0.61) and in fibroblasts (26 nmol.min l.mg protein 1 normal range 14-118) was normal, whereas the small increase of activity in platelets (59.5 nmol.min . 10 cells control 26.7) and in the liver (8.4 pmol.min . mg protein" normal ... 

At the present time, we just report some experimental results of a study on the mechanism of action of allopurinol (U-hydroxy-pyrazolo (3, -d ) pyrimidine) and thiopurinol k thiopyrazolo (3, d) pyrimidine) on de novo biosynthesis of uric acid. In this present work, we have compared effect of alio and thiopurinol on oxypurine (xanthine and hypoxanthine) urinary excretion with their rate of synthesis of ribonucleotides in vitro by erythrocyte hemolysate in some particular enzymatic deficiencies (hypoxanthine-guanine phosphoribosyltransferase HGPRT, adenine phosphoribosyl-transferase APRT and xanthinuria). 

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