Purine Overproduction in Man Associated with Increased Phosphoribosylpyrophosphate Synthetase Activity

  title={Purine Overproduction in Man Associated with Increased Phosphoribosylpyrophosphate Synthetase Activity},
  author={Michael A. Becker and L. J. Meyer and Alexander W. Wood and J. Edwin Seegmiller},
  pages={1123 - 1126}
In hemolyzates from red cells of two brothers with purine overproduction and gout, activity of phosphoribosylpyrophosphate synthetase is more than twofold greater than that measured in normal or other gouty individuals. The increased enzyme activity, which is also demonstrable in fibroblasts of the one patient tested, is associated with increased production of 5-phosphoribosyl-1-pyrophosphate by intact cells, an indication that the enzyme abnormality is the basis for the purine overproduction… 

Increased PP-ribose-P synthetase activity: a genetic abnormality leading to excessive purine production and gout.

Another hereditary abnormality of biochemistry has now been described in two families in which purine overproduction and clinical gout are associated with an increased, rather than a decreased, activity of a specific enzyme.

Abnormal purine and pyrimidine metabolism in inherited superactivity of PRPP synthetase.

The biochemical abnormalities in a patient with PRPPS superactivity was investigated and changes in nucleotide and nucleoside profiles were investigated.

Phosphoribosylpyrophosphate synthetase superactivity. A study of five patients with catalytic defects in the enzyme.

Findings support the concept that enzyme superactivity results in uric acid overproduction as a consequence of increased rates of PRPP and purine nucleotide synthesis.

Superactivity of phosphoribosylpyrophosphate synthetase, due to feedback resistance, causing purine overproduction and gout.

A mutant feedback-resistant, physiologically superactive, phosphoribosylpyrophosphate (PP-ribose-P) synthetase was found in a family with purine overproduction, gout and uric acid lithiasis, indicating an X-linked pattern of inheritance of the synthet enzyme superactivity in this gouty family.

Phosphoribosylpyrophosphate overproduction, a new metabolic abnormality in the Lesch Nyhan syndrome

The activity of phosphoribosylpyrophosphate synthetase and the rate of phosphoribosylpyrophosphate accumulation are significantly increased in cultured lymphocytes of Lesch Nyhan patients deficient

Mutant feedback-resistant phosphoribosylpyrophosphate synthetase associated with purine overproduction and gout. Phosphoribosylpyrophosphate and purine metabolism in cultured fibroblasts.

F fibroblast studies demonstrate the following sequence of abnormalities: feedback-resistance of PRPP synthetase; superactivity of this enzyme in normal physiological milieu; increased availability ofPRPP; and increased de novo synthesis of purine nucleotides.

Gout with superactive phosphoribosylpyrophosphate synthetase due to increased enzyme catalytic rate.

It is suggested that increased intracellular synthesis dut to enzyme superactivity underlay purine nucleotide and uric acid overproduction in these patients, and distinct structural alterations leading to enzymes superactivity in families C and A are suggested.

IMP dehydrogenase mutants: cell culture model for hyperuricemia.

  • B. Ullman
  • Biology, Medicine
    Advances in experimental medicine and biology
  • 1984
These studies with wild-type and mutant cells defective in IMP dehydrogenase and the previous data with the adenylosuccinate synthetase-deficient cell line suggest that among the clinical population



Depletion of erythrocyte phosphoribosylpyrophosphate in man.

The findings that allopurinol depletes PRPP and is apparently converted to its ribonucleotide in vivo suggest that this widely used drug may have a variety of biochemical effects in addition to xanthine oxidase inhibition.

Heme biosynthesis in intermittent acute prophyria: decreased hepatic conversion of porphobilinogen to porphyrins and increased delta aminolevulinic acid synthetase activity.

A micro-radio-chemical assay of delta-aminolevulinic acid synthetase, and some of its applications, are described, and this first and rate-controlling enzyme in the biosynthetic pathway is subject to negative feedback regulation by the end product, heme.

Enzyme Defect Associated with a Sex-Linked Human Neurological Disorder and Excessive Purine Synthesis

This work has demonstrated the first relationship between a specific enzyme defect and abnormal compulsive behavior in a neurological disease and the production of excessive uric acid in this disorder implies that the enzyme is involved in the normal regulation of purine biosynthesis.

Rate-limiting steps in the interconversion of purine ribonucleotides in Ehrlich ascites tumor cells in vitro.

The conversion of inosinate to guanylate in Ehrlich ascites tumor cells incubated in vitro in Krebs-Ringer phosphate medium is limited first by the concentration of glutamine and then by the

Substrate Stabilization: Genetically Controlled Reciprocal Relationship of Two Human Enzymes

The increased activity of adenine phosphoribosyltransferase seen in erythrocytes deficient in hypoxanthine-guanine phosphorosyl transferase may result from substrate stabilization of this enzyme in vivo.