Superactivity of Phosphoribosylpyrophosphate Synthetase, due to Feedback Resistance, Causing Purine Overproduction and Gout

Oded Sperling*, Pnina Boer, Sara Brosh, Esther Zoref, André de Vries

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


A mutant feedback-resistant, physiologically superactive, phos phoribosylpyr ophosphate (PP-ribose-P) synthetase was found in a family with purine overproduction, gout and uric acid lithiasis. In haemolysates and cultured fibroblasts from the propositus, the mutant enzyme exhibited resistance to feedback inhibition by normal cell constituents, such as ADP and GDP; normal affinity to substrates and to activator P1 was demonstrated in the haemolysate. In both erythrocytes and cultured fibroblasts, the superactivity of the mutant enzyme was manifest in increased PP-ribose-P content and availability for nucleotide synthesis, leading to an acceleration of the rate of purine synthesis de now in the fibroblasts. The enzyme abnormality and the resulting increase in PP-ribose-P content and generation were demonstrated in the erythrocytes of one of the propositus' two siblings who was similarly affected but not in the propositus' father, his second brother and four sons, who were all clinically and biochemically normal, nor in the erythrocytes of the clinically normal hyperuricosuric mother. However, cultured fibroblasts from her skin exhibited variability in PP-ribose-P content and availability and in the rate of purine synthesis de now, these parameters being increased in most cultures. The mother's fibroblast cultures were found to contain two cell populations, one with normal and the other with mutant PP-ribose-P synthetase, indicating an X-linked pattern of inheritance of the synthetase superactivity in this gouty family.

Original languageEnglish
Title of host publicationPurine and Pyrimidine Metabolism
Number of pages22
ISBN (Electronic)9780470720301
ISBN (Print)9789021940540
StatePublished - 30 May 2008


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