Purine metabolism in normal and ITP-pyrophosphohydrolase-deficient human erythrocytes.
Fresh and stored erythrocytes from normal and ITP-pyrophosphohydrolase (ITP-ase, EC 3.6.1.19) deficient individuals were incubated with hypoxanthine, guanine, allopurinol, and inosine. Differences in the purine metabolism between the normal and the ITP-ase deficient erythrocytes were observed only in the IMP-ITP cycle. Hypoxanthine, guanine and allopurinol were converted to nucleotides at the same rate. Hypoxanthine (2.5 mumol/l) inhibited the salvage of allopurinol (40 mumol/l). A slow decrease (0.7%/day) in salvage rate was observed in both types of cells upon storage at +4 degrees C. Erythrocyte ITP-ase activity was measured in a reference sample group of 48 healthy volunteers. Two distinct groups were found with mean activities equal to 48.3 +/- 13.1 nkat/g Hb (means +/- SD, n = 38) and 11.4 +/- 4.3 nkat/g Hb (n = 10). In two previously selected subjects, the ITP-ase activity was 0.2 and 2.4 nkat/g Hb. A hypothetical genetic mechanism is discussed. The maximal energy turnover in the IMP-ITP cycle during hypoxanthine incubation was found to be less than 10% of the basal erythrocyte energy turnover.
van Waeg
G
G
Departmet of Clinical Chemistry, Uppsala University, Akademiska Sjukhuset, Sweden.
Niklasson
F
F
Ericson
A
A
de Verdier
C H
CH
D000493:Allopurinol / Q000097:blood; D002478:Cells, Cultured; D004734:Energy Metabolism; D004912:Erythrocytes / Q000201:enzymology*; D006147:Guanine / Q000097:blood; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000097:blood; D011687:Purines / Q000097:blood*; D011755:Pyrophosphatases / Q000172:deficiency*; D013048:Specimen Handling; D000097630:Inosine Triphosphatase
D000493:Allopurinol; D006147:Guanine; D019271:Hypoxanthine; D007042:Hypoxanthines; D011687:Purines; D011755:Pyrophosphatases; D000097630:Inosine Triphosphatase