Uricolysis in Normal and Gouty Individuals

Bień, E; Zucker, Mordecai

doi:10.1136/ard.14.4.409

Cited by 15 publications

(3 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A diminished uricolysis has been postulated as a cause of hyperuricemia (33). The essentially complete recovery in the urine of intravenously administered uric acid-N"5 in Patient J.F.…”

Section: Discussionmentioning

confidence: 99%

Uric Acid Metabolism in Psoriasis

Eisen¹,

Seegmiller²

1961

J. Clin. Invest.

View full text Add to dashboard Cite

Hyperuricemia has been noted to occur in approximately 30 to 40 per cent of patients with psoriasis (1-5). The cause of the hyperuricemia and its possible relation to the psoriatic process has received very little attention.Uric acid synthesis has been evaluated in man by determining the turnover of injected isotopically labeled uric acid as well as by the incorporation of isotopically labeled glycine into urinary uric acid. Observations made on subjects with primary gout have shown that there is a prompt incorporation of glycine-l-C14 or glycine-N'5 into urinary uric acid (6-13) while in gout secondary to proliferative disorders of the hemopoietic system, isotopic incorporation is delayed presumably because the major pathway of uric acid synthesis involves the incorporation of glycine into tissue purines with their slower rate of turnover (14,15).In psoriasis, the skin lesion is a result of hyperplasia of the epidermis in which the rate of cellular reproduction is accelerated to such an extent that maturation of the epidermal cells and the process of normal keratinization do not occur (16). By analogy with the hyperuricemia seen in myeloproliferative diseases, it is possible that the hyperuricemia of psoriasis may reflect an increased nucleic acid turnover resulting from the marked acceleration of epidermal proliferation that occurs in this disease.The present study was undertaken to determine whether the pattern of glycine-l-C14 incorporation control subjects. The patient with gout and psoriasis (F.M.) had a history of frequent attacks of acute arthritis which responded to colchicine. A synovial biopsy of his left knee revealed characteristic deposition of urate crystals. The control subjects had no family history or stigmata of either psoriasis or gout. Remission of psoriasis occurred in one patient (L.P.) following a severe drug eruption resulting from the oral administration of chloroquin phosphate. Within 2 weeks after the drug had been discontinued, complete healing of the skin had occurred and no lesions of psoriasis were present. The repeat glycine-1-C1' incorporation study was carried out approximately 10 weeks after the last dose of chloroquin had been administered, while the psoriasis was still in complete remission.All subjects were hospitalized throughout the studies and were maintained on a standard 2,600 calorie diet, essentially free of purines and containing 70 g of protein, 350 g of carbohydrate and 100 g of fat. At least 5 days were allowed for equilibration on the diet before the studies were performed. Patients received no medication during the study. The clinical diagnosis of psoriasis in each case was confirmed by skin biopsy. Renal function was assessed by routine urinalysis, blood urea nitrogen and phenolsulfonphthalein excretion.Daily 24-hour urine collections were preserved with toluene and stored at room temperature. Serum and urinary uric acid determinations were performed by means of the enzymatic spectrophotometric assay of Praetorius and Poulsen (17) as modified by Liddle, Seegm...

show abstract

“…A diminished uricolysis has been postulated as a cause of hyperuricemia (33). The essentially complete recovery in the urine of intravenously administered uric acid-N"5 in Patient J.F.…”

Section: Discussionmentioning

confidence: 99%

Uric Acid Metabolism in Psoriasis

Eisen¹,

Seegmiller²

1961

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…And since the turnover time of ribonucleic acids is about 8 to 10 days, and of desoxyribonucleic acids even longer (24), the prompt enrichment of urinary uric acid could not have proceeded via nucleic acids. Some of the mechanisms permitting this prompt direct entry of isotope into urinary uric acid, which obviously occurs to a limited extent also in normal subjects, are currently under study (8,25 The uric acid not excreted via the kidney has three quantitatively important fates available to it: deposition in tophi, excretion by way of bile and gastrointestinal tract (29), and destruction in tissues (30,31). Two of our patients (D. W. and V. L.) were observed to develop tophi about the time the studies were performed.…”

Section: Discussionmentioning

confidence: 99%

Overproduction of Uric Acid as the Cause of Hyperuricemia in Primary Gout

Wyngaarden¹

1957

J. Clin. Invest.

View full text Add to dashboard Cite

Glycine contributes carbon atoms 4 and 5 and nitrogen atom 7 of the purine ring (1-3). Benedict, Yfi, Bien, Gutman and Stetten (4) have described experiments in which the abundance of N15 in uric acid was measured for several days following an oral test dose of glycine-N'5. In two gouty subjects, three times as much of the administered N15 was recovered in urinary uric acid as in normal subjects. In two others, however, normal quantities of N15 appeared in uric acid. In these studies, there was a rank order correlation between the daily excretion of uric acid in the urine and the per cent of ingested isotope appearing in urinary uric acid. In subjects who exhibited abnormally high basal uric acid excretions, an abnormally rapid and excessive incorporation of dietary glycine into uric acid occurred. In others whose basal excretion was approximately normal, utilization of glycine for uric acid synthesis was normal. Muller and Bauer (5) and Bishop, Rand, and Talbott (6) have each reported an additional gouty patient excreting normal quantities of uric acid who incorporated normal quantities of glycine-N'5 into urinary uric acid. The latter authors also described one gouty patient who incorporated excessive quantities of glycine-N'5 into urinary uric acid on two of three occasions despite a normal urinary urate excretion. These studies, therefore, demonstrated that overproduction of uric acid was present in some gouty subjects, but failed to give a clear indication of the cause of hyperuricemia in another, perhaps predominant group of the gouty population.Recently, we have administered glycine-1-C'4 to control and gouty patients in order to label urinary purines, as part of a study of intermediates in urate synthesis (7). The first two gouty patients both exhibited excessive incorporation of C14 into urinary urate, one despite a normal urate excretion (7,8). It was therefore decided to re-investigate the problem of the rate of generation of uric acid in gout, employing tracer doses of glycine-1-C"4 rather than large doses of glycine-N'5 as were required in previous studies.In the present study, glycine-1-C'4 was administered orally in 2.5 to 25 uc. doses to control and gouty subjects, and the concentration and cumulative incorporation of isotope into urinary uric acid were determined. This paper presents data indicating that overincorporation of glycine-1-C'4 into uric acid is a consistent finding in primary gout, and that the failure of the glycine-N'5 technique to disclose overincorporation in some gouty subjects may have been the result of the large dose of glycine employed. These results have been interpreted as showing that the hyperuricemia of primary gout is due to overproduction of uric acid in the majority if not all gouty subjects. METHODSGlycine-1-C'4, specific activity 1 to 2 mc. per mM, was purchased from Nuclear Instrument and Chemical Company. Uric acid determinations were performed by differential spectrophotometry according to Praetorius (9), employing purified uricase purchased from Worthington Bio...

show abstract

“…Nachdem wir den erhöhten Harnsäurcanfall aus dem Nukleinsäurestoffwechsel bei E r krankungen m it verm ehrtem Zellzerfall (in erster Linie des myelo ischen Systems) entsprechend Gutrnan [20] als sekundäre Gicht -mit relativ seltenen M anifestationen trotz z. T. sehr hohen Seruinwertenvon der genetisch fixierten primären Gicht abgrenzen, nachdem wei ter die Frage einer gewissen urikolytischen Fähigkeit auch mensch licher Gewebe zwar zu bejahen ist [5,[25][26][27][28], der Gichtkranke sich aber kaum anders verhält als der Gesunde, und nachdem Verminde rungen der enteralen Ausscheidungsquote von normalerweise 40-80 mg pro Tag [22], die Brugsch 1922 m it seiner «enterotropischen Gichttheorie» verm utete [21], als Ursache der Gicht wohl ausgeschloßen sind [23] [47,48], und zwar sicher nicht bedingt durch eine sekun däre Nierenschädigung als Folge der Gicht. Eine verm inderte Elim i nationsfähigkeit für H arnsäure, wahrscheinlich über eine tubuläre Sekretionshemmung, mag also beim Gichtkranken bestehen oder hinzukom m en; ob sie das generelle prim äre pathogenetische Moment bei allen Gichtkranken darstellt, muß noch für fraglich gehalten wer den.…”

Section: Schwartingunclassified

Die Gicht

Schwarting¹

1962

Digestion

View full text Add to dashboard Cite

Uricolysis in Normal and Gouty Individuals

Cited by 15 publications

References 5 publications

Uric Acid Metabolism in Psoriasis

Uric Acid Metabolism in Psoriasis

Overproduction of Uric Acid as the Cause of Hyperuricemia in Primary Gout

Die Gicht

Contact Info

Product

Resources

About