Purine absorption and excretion

THE EFFECT OF ALLOPURINOL ON ORAL PURINE ABSORPTION AND EXCRETION IN THE PIG... 

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. 

A. Pernicious anemia occurs when the stomach does not produce adequate intrinsic factor for absorption of vitamin B12, which is required for the conversion of methylmalonyl CoA to succinyl CoA and homocysteine to methionine. A vitamin B12 deficiency results in the excretion of methylmalonic acid and an increased dietary requirement for methionine. The methyl group transferred from vitamin B12 to homocysteine to form methionine comes from 5 -methyl tetrahydrofolate, which accumulates in a vitamin B12 deficiency, causing a decrease in folate levels and symptoms of folate deficiency, including increased levels of FIGLU and decreased purine biosynthesis. 

To summarize the data on endogenous uric acid production and on purine supplementation experiments, it would appear that on an average diet about half the urinary uric acid and one-third of the plasma uric acid is derived from dietary purine compounds in normal man. These contribute to the increase in serum uric acid and renal excretion of uric acid according to the velocity of their enzymatic hydrolysis within the intestine and also according to their solubility and degree of absorption. 

Similar experiments using intravenous C guanine have been carried out to determine whether allopurinol produces this effect by blocking absorption or enhancing purine excretion into the gut. In these experiments 13% of the intravenously administered label was excreted into the gut during allopurinol therapy, and less than 1% was found in the faeces when guanine was given alone. However, respiratory C02 was measured for only the first t onty-four hours in these experiments, and these results therefore require to be substantiated. 

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