Uric Acid Abstracts 1 - Glycine

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A further study of the utilization of dietary glycine nitrogen for uric acid synthesis in gout

         (Benedict, Yu et al. 1953) Download

The concentrations of N15 in urinary uric acid following the ingestion of a single test dose of glycine-N'5. In subjects who exhibited abnormally high basal uric acid excretions, an abnormally rapid incorporation of dietary glycine nitrogen into uric acid occurred. In others whose basal excretion was approximately normal,no such evidence of accelerated uric acid synthesis was  ddemonstrable.

The relation of dietary nitrogen consumption to the rate of uric acid synthesis in normal and gouty man

         (Bien, Yu et al. 1953) Download

Both in the normal and in the gouty subject, uric acid synthesis was found to be accelerated when the diet was fortified with protein. This acceleration was approximately paralleled by an acceleration in other metabolic pathways of glycine.

The Effect Of The Ingestion Of Glycine On The Excretion Of Endogenous Uric Acid

         (Christman and Mosier 1929) Download

After the collection of two control samples, 10 gm. of glycine were ingested and the hourly collection continued for the following 5 hours.

Our results then are in accordance with the work of Lewis, Dunn, and Doisy; that is, the ingestion of glycine produces a distinct rise in the uric acid excretion.

In confirmation of the work of Lewis, Dunn, and Doisy (2) these results show that the ingestion of glycine by a fasting man is followed by an increased hourly excretion of uric acid. This effect is noted during the 1st hour after the ingestion of the glycine and continues for the following 2 hours.


The Effect of Glycine on the Production and Excretion of Uric Acid

         (Friedman 1947) Download

The above results suggest quite strongly that glycine does not increase the production of uric acid in the body of either rat or man. On the other hand it was certain from the observations made that glycine ingestion does increase the renal excretion of uric acid.

The failure of the blood uric acid to decrease in the presence of this increased renal output of uric acid may well be due to the ability of the extra- vascular tissues to maintain the blood uric acid concentration despite its increased renal excretion.

A Note On The Effect Of Some Organic Acids Upon The Uric Acid Excretion Of Man

         (Gibson and Doisy 1923) Download

The ingestion of sodium salts of lactic acid causes a decrease, and of pyruvic acid an increase in the excretion of uric acid.

Amino acid excretion in primary hyperuricaemia

         (Kaplan, Diamond et al. 1969) Download

This study has demonstrated that the clearance of several amino acids by the kidneys of hyperuricaemic subjects is diminished. Hyperuricaemia alone does not appear to be the cause of the altered amino acid clearance. It is suggested that the renal tubular cells in hyperuricaemic persons have a defect in transport mechanisms leading to a reduction in secretion of both uricacid and certain amino acids.

Sur La Genese Du Glycocolle Lors De L'Intoxication Benzoique

         (Lombroso, Zummo et al. 1934) Download

The study of human intermediary purine metabolism and its regulation

         (Seegmiller 1966) Download

Human purine synthesis may be regulated by a relative feedback control system.


On The Utilization Of Glycine For Uric Acid Synthesis In Man

         (Shemin and Rittenberg 1947) Download

The carbon atom at position 7 of uric acid arises specifically from glycine.

Uric acid changes in urine and plasma: an effective tool in screening for purine inborn errors of metabolism and other pathological conditions

         (Simoni, Gomes et al. 2007) Download

Purine inborn errors of metabolism (IEM) are serious hereditary disorders, which should be suspected in any case of neonatal fitting, failure to thrive, recurrent infections, neurological deficit, renal disease, self-mutilation and other manifestations. Investigation usually starts with uric acid (UA) determination in urine and plasma. UA, the final product of purine metabolism in humans, may be altered not only in purine IEM, but also in other related pathologies and clinical conditions. However, data and information about abnormal UA levels are scattered in the literature, often being controversial and confusing. A comprehensive overview has been elaborated, according to abnormal UA levels in urine and plasma, which associates these alterations with purine IEM. Other possible diseases, clinical conditions, diet and drug intake, related to the metabolism of uric acid, are also presented. The article includes tables that classify the disorders according to different patterns of UA alterations, with pertinent enzymes, clinical symptoms, inheritance and comments. Additionally, summarized pathophysiological mechanisms of important disorders are described. The overview is intended to assist in the interpretation of the results of UA analyses. It demonstrates that variation of UA concentrations in urine and plasma may constitute an effective tool in screening for purine IEM and other related pathological conditions.


The kinetics of intramolecular distribution of 15N in uric acid after administration of (15N) glycine. A reappraisal of the significance of preferential labeling of N-(3+9) of uric acid in primary gout

         (Sperling, Wyngaarden et al. 1973) Download

THE CONCEPT OF AN ABNORMALITY OF GLUTAMINE METABOLISM IN PRIMARY GOUT WAS FIRST PROPOSED ON THE BASIS OF ISOTOPE DATA: when [(15)N]glycine was administered to gouty subjects, there was disproportionately great enrichment of N-(3 + 9) of uric acid, which derive from the amide-N of glutamine. An unduly high concentration of (15)N in glutamine was postulated, and attributed to a hypothetical defect in catabolism of glutamine. Excess glutamine was proposed as the driving force of uric acid overproduction. WE HAVE REEXAMINED THIS PROPOSITION IN FOUR GOUTY SUBJECTS: one mild overproducer of uric acid with "idiopathic gout," one marked overproducer with high-grade but "partial" hypoxanthine-guanine phosphoribosyl-transferase deficiency, and two extraordinary overproducers with superactive phosphoribosylpyrophosphate synthetases. In the last three, the driving force of excessive purine biosynthesis is a known surplus of alpha-5-phosphoribosyl-1-pyrophosphate. Disproportionately high labeling of N-(3 + 9) was present in all four gouty subjects, most marked in the most flamboyant overproducers. The precursor glucine pool was sampled by periodic administration of benzoic acid and isolation of urinary hippuric acid. Similarly, the precursor glutamine pool was sampled by periodic administration of phenylacetic acid and isolation of the amide-N of urinary phenylacetylglutamine. The time course of (15)N enrichment of hippurate differed from that of the amide-N of glutamine. Whereas initial enrichment values of hippurate were very high, those of glutamine-amide-N were low, increasing to a maximum at about 3 h, and then declining less rapidly than those of hippurate. However, enrichment values of hippurate and of phenacetyl glutamine were normal in all of the gouty subjects studied. Thus, preferential enrichment of N-(3 + 9) in gouty overproducers given [(15)N]glycine does not necessarily reflect a specific abnormality of glutamine metabolism, but rather appears to be a kinetic phenomenon associated with accelerated purine biosynthesis per se.In addition, greater enrichment of N-9 than of N-3 on days 1 and 2 provided suggestive evidence for a second pathway for synthesis of the initial precursor of purine biosynthesis, phosphoribosylamine, perhaps utilizing ammonia rather than the amide-N of glutamine as nitrogen donor. In this limited study, the activity of this potential second pathway did not appear to be selectively increased in gout.


Hyperuricaemia: some biochemical aspects

         (Watts 1969) Download

It should be emphasized that a clear-cut abnormality of enzyme activity has so far been demonstrated only in a minority of hyperuricemic patients, even among those with evidence of excessive purine biosynthesis.

Overproduction of uric acid as the cause of hyperuricemia in primary gout

         (Wyngaarden 1957) Download

These results constitute strong evidence that overproduction of uric acid from glycine and other small molecules is the fundamental defect responsible for the hyperuricemia of primary gout.

Glycine in the Treatment of Gout

         (Wrigley 1950) Download

The use of glycine and salicylate in the treatment of gout has now become fairly well established. This paper is to suggest a reconsideration of this form of therapy.

One might think there is not in these studies sufficient evidence to justify the administration of glycine to a case of gout. Later evidence points to the fact that the administration of glycine may actually promote the formation of uric acid.

Effect of glycine loading on plasma and urinary uric acid and amino acids in normal and gouty subjects

         (Yu, Kaung et al. 1970) Download

A single oral dose of glycine, 100 mg/kg body weight, a "physiologic" load, was given to ten normal men and seventeen patients with primary gout. The ensuing uricosuria, chiefly due to increased renal clearance of uric acid, was relatively greater in the gouty subjects.


References

Benedict, J. D., T. F. Yu, et al. (1953). "A further study of the utilization of dietary glycine nitrogen for uric acid synthesis in gout." J Clin Invest 32(8): 775-7 PMID: 13069625

Bien, E. J., T. F. Yu, et al. (1953). "The relation of dietary nitrogen consumption to the rate of uric acid synthesis in normal and gouty man." J Clin Invest 32(8): 778-80 PMID: 13069626

Christman, A. A. and E. C. Mosier (1929). "The Effect Of The Ingestion Of Glycine On The Excretion Of Endogenous Uric Acid." J. Biol. Chem. 83: 11-19 PMID:

Friedman, M. (1947). "The Effect of Glycine on the Production and Excretion of Uric Acid." J Clin Invest 26(4): 815-9 PMID: 16695473

Gibson, H. V. and E. A. Doisy (1923). "A Note On The Effect Of Some Organic Acids Upon The Uric Acid Excretion Of Man." J. Biol. Chem. 66: 605 PMID:

Kaplan, D., H. Diamond, et al. (1969). "Amino acid excretion in primary hyperuricaemia." Ann Rheum Dis 28(2): 180-6 PMID: 5777248

Lombroso, U., C. Zummo, et al. (1934). "Sur La Genese Du Glycocolle Lors De L'Intoxication Benzoique." Arch Int Physiol 39(1) PMID:

Seegmiller, J. E. (1966). "The study of human intermediary purine metabolism and its regulation." Proc R Soc Med 59(4): 292-302 PMID: 5327976

Shemin, D. and D. Rittenberg (1947). "On The Utilization Of Glycine For Uric Acid Synthesis In Man." J. Biol. Chem. 167: 875-876 PMID:

Simoni, R. E., L. N. Gomes, et al. (2007). "Uric acid changes in urine and plasma: an effective tool in screening for purine inborn errors of metabolism and other pathological conditions." J Inherit Metab Dis 30(3): 295-309 PMID: 17520339

Sperling, O., J. B. Wyngaarden, et al. (1973). "The kinetics of intramolecular distribution of 15N in uric acid after administration of (15N) glycine. A reappraisal of the significance of preferential labeling of N-(3+9) of uric acid in primary gout." J Clin Invest 52(10): 2468-85 PMID: 4353999

Watts, R. W. (1969). "Hyperuricaemia: some biochemical aspects." Proc R Soc Med 62(8): 853-7 PMID: 5810320

Wrigley, F. (1950). "Glycine in the Treatment of Gout." Ann Rheum Dis 9(1): 38-42 PMID: 18623833

Wyngaarden, J. B. (1957). "Overproduction of uric acid as the cause of hyperuricemia in primary gout." J Clin Invest 36(10): 1508-15 PMID: 13475488

Yu, T. F., C. Kaung, et al. (1970). "Effect of glycine loading on plasma and urinary uric acid and amino acids in normal and gouty subjects." Am J Med 49(3): 352-9 PMID: 5455567