Uric acid hypothesis

Lithium became a popular medicinal substance under the influence of the uric acid hypothesis. Proprietary medicines, tonics and fashionable mineral spas were advertised as containing lithium and other recommended antidotes to uric acid. Lithium was even put into beer and the drink 7 UP started life as a lithium drink (Healy 2002) (see Illustration 11.1). 

Ames, B.N., Cathcan, B, Schwiers, E. and Hochstein, P. (1981). Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer a hypothesis. Proc. Natl Acad. Sci. USA 78, 6858-6862. 

It remains to be clarified why patients with renal hypouricemia frequently develop acute renal failure. The following hypothesis has been proposed. Oxidative stress is essential for the onset of ischemic acute renal failure. In the kidney, uric acid acts as a protective mechanism against oxidative stress. However, in patients with renal hypouricemia, a decrease in uric acid may allow exposure of the kidney to oxidative stress, causing ALPE [152,153]. 

Fay RA. Uric acid in pregnancy and preeclampsia an alternative hypothesis. Aust NZ J Obstet Gynaecol 1990 30 141-2. 

The response of serum and urine uric acid to different kinds of dietary purines v/as explained by the hypothesis that RNA and DNA have to be degraded to their nucleotides (and possibly nucleosides) prior to absorption, and that different absorption might be due to a different velocity of degradation. This results in a renai excretion of the purines administered orally of about 25 percent in the case of DNA, 50 percent with RNA, and 80 percent with nucleotides (Zollner et al., 1972). The conclusion drawn from these results was that only nucleotides are absorbed from the gut completely. 

If there is an increased uric acid synthesis as well as an additional enhancement of renal excretion, one might expect constant serum levels of uric acid while excretion increases. In agreement with this hypothesis, there were publications which showed a considerable increase in renal excretion of uric acid and at the same time only slight or no variations in serum levels (Bowering et al., 1969). 

Summerizing it can be said that a higher percentage of the patients with uric acid stones have an increased P2 -microglobulin excretion than patients suffering from oxalate stones. Furthermore our study shows that in this group of patients Uromucoid, GAG, and Citrate excretion are decreased. We think that our findings must be interpreted in the way that tubular defects in patients with uric acid stones are not rare. It seems that the acidification, reabsorption, and the decrease of the acid mucoprotein in the urine support this hypothesis. 

A more widely accepted scheme for uric acid synthesis was proposed in 1902 by Wiener. In this hypothesis urea was condensed with hydroxy-... 

Uric acid accumulation could result from underexcretion of purines, either as a result of excessive reabsorption in the tubules (see above), or because of the presence of a noncompetitive inhibitor of the carrier of urates through the epithelial membrane in the process of secretion. There is no direct evidence for such a hypothesis, but the plotted curves representing the changes in uric acid content in the urine for a given level of uric acid in the blood are compatible with it. Relevant to this assumption is an observation made on uric acid excretion in salivary glands the secretion of urate in saliva is lower in patients with gout than in normal individuals. 

Our patient had basal hypouricemia due to renal urate overexcretion. Renal leak of other substances and inappropriate secretion of ADH were ruled out. Pentagastrin injection elevated plasma calcitonin with simultaneous increment of urate fractional excretion and diminution of serum uric acid, lending support to the hypothesis... 

The glycine incorporation studies performed in two subjects support the hypothesis that purine biosynthesis is not inhibited by oral purine administration. Cumulative renal excretion of 15 N as uric acid over 11 days is shown in Figure 1 and 2. After correction of renal uric acid excretion for extrarenal excretion, in Subject 4 15 N excretion was 0.29 percent of the dose given orally during purine-free diet and 0.28 percent during purine supplementation. Corresponding values in Subject 5 were 0.22 and 0.26 percentjrespec-tively. 

THE KINETICS OF INTRAMOLECULAR DISTRIBUTION OF in URIC ACID FOLLOWING ADMINISTRATION OF N-GLYCINE PREFERENTIAL LABELING OF N-(3+9) OF URIC ACID IN PRIMARY GOUT AND A REAPPRAISAL OF THE "GLUTAMINE HYPOTHESIS"... 

Our observations are most consistent with the hypothesis that the infusion of fructose leads to a rapid degradation of purine nucleotides with the consequent formation of inosine, hypoxanthine, xanthine, and finally uric acid (Fig. 6. Recent studies in the rat in vivo (Raivio, Kekomaki, and Maenpaa,... 

Since ATP normally inhibits 5 -nucleotidase and inorganic phosphate inhibits AMP deaminase, these changes would be expected to stimulate the catabolism of AMP to inosine. This hypothesis would most readily account for the rapid rise in serum urate concentration, the increased urinary excretion of inosine, oxypurines and uric acid, and the lack of an increase in intracellular PP-ribose-P levels following fructose infusion. 

PEPP "generation most likely is influenced by formation of inhibitors for PRPP synthetase, like AMP. This could further favour our hypothesis of a rapid breakdown of purine nucleotides being the cause of xylitol-induced uric acid increase. 

There are two methylated uric acids which are considered by Wanner et aL (1975) to be the first products of caffeine degradation. They are testing that hypothesis. This is a particularly attractive hypothesis since the two isolated methylated uric acids were not detected before in any Coffea species. These were 2-methoxy-l,9-dimethyl-7,9-dihydro-l//-pur-... 

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