Literature DB >> 682520

[The influence of allopurinol on purine- and pyrimidinesynthesis (author's transl)].

W Gröbner, N Zöllner.   

Abstract

Allopurinol inhibits xanthinoxydase. This results in a decrease of the serum and urinary uric acid. Simultaneously the renal excretion of hypoxanthine and xanthine increases. In most patients, however, the decrease of urinary uric acid is not completely replaced by the increase of oxypurines. This is attributed to an additional inhibition of de novo purine biosynthesis. The different effect of allopurinol on the endogenous and exogenous urates offers an alternative approach to explain the "purine deficit". The effect of allopurinol on the pyrimidine metabolism is due to an inhibition of orotidylic decarboxylase by the ribonucleotides of allopurinol, xanthine and oxipurinol. This inhibition is followed by an increase in the urinary excretion of orotidine and orotic acid. The additional administration of ribonucleic acid leads to a striking decrease of the allopurinol induced orotaciduria. The continuous administration of allopurinol also produces an increase in the activity of orotate phosphoribosyltransferase and orotidylic decarboxylase. At this time the mechanism of this increase in activity is not completely understood. Allopurinol is metabolized rapidly. Only 3-10% of an administered dose are excreted unchanged in the urine. Most of the allopurinol is oxidized to oxipurinol. A small portion is converted to the ribonucleosides and ribonucleotides1 of allopurinol and oxipurinol.

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Year:  1978        PMID: 682520

Source DB:  PubMed          Journal:  Klin Wochenschr        ISSN: 0023-2173


  29 in total

1.  Effect of allopurinol and its metabolic derivatives on the configuration of human orotate phosphoribosyltransferase and orotidine 5'-phosphate decarboxylase.

Authors:  W Grobner; W N Kelley
Journal:  Biochem Pharmacol       Date:  1975-02-01       Impact factor: 5.858

2.  PSEUDOFEEDBACK INHIBITION OF PURINE SYNTHESIS BY 6-MERCAPTOPURINE RIBONUCLEOTIDE AND OTHER PURINE ANALOGUES.

Authors:  R J MCCOLLISTER; W R GILBERT; D M ASHTON; J B WYNGAARDEN
Journal:  J Biol Chem       Date:  1964-05       Impact factor: 5.157

3.  HEREDITARY OROTIC ACIDURIA AND MEGALOBLASTIC ANAEMIA: A SECOND CASE, WITH RESPONSE TO URIDINE.

Authors:  D M BECROFT; L I PHILLIPS
Journal:  Br Med J       Date:  1965-02-27

4.  Augmentation of the incorporation of hypoxanthine into nucleic acids by the administration of an inhibitor of xanthine oxidase.

Authors:  R POMALES; S BIEBER; R FRIEDMAN; G H HITCHINGS
Journal:  Biochim Biophys Acta       Date:  1963-05-28

5.  Refractory megaloblastic anemia associated with excretion of orotic acid.

Authors:  C M HUGULEY; J A BAIN; S L RIVERS; R B SCOGGINS
Journal:  Blood       Date:  1959-06       Impact factor: 22.113

6.  Human glutamine phosphoribosylpyrophosphate amidotransferase. Kinetic and regulatory properties.

Authors:  E W Holmes; J A McDonald; J M McCord; J B Wyngaarden; W N Kelley
Journal:  J Biol Chem       Date:  1973-01-10       Impact factor: 5.157

7.  An enzymatic basis for variation in response to allopurinol. Hypoxanthine-guanine phosphoribosyltransferase deficiency.

Authors:  W N Kelley; F M Rosenbloom; J Miller; J E Seegmiller
Journal:  N Engl J Med       Date:  1968-02-08       Impact factor: 91.245

8.  Allopurinol: alteration in pyrimidine metabolism in man.

Authors:  W N Kelley; T D Beardmore
Journal:  Science       Date:  1970-07-24       Impact factor: 47.728

9.  Allopurinol in the treatment of gout.

Authors:  R W Rundles; E N Metz; H R Silberman
Journal:  Ann Intern Med       Date:  1966-02       Impact factor: 25.391

10.  Effect of dietary purine restriction, allupurinol, and oxipurinol on urinary excretion of ultraviolet-absorbing compounds.

Authors:  W N Kelley; J B Wyngaarden
Journal:  Clin Chem       Date:  1970-08       Impact factor: 8.327

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