The effect of RNA supplementation of rat diets on the composition of body fluids

Abstract

1. In a number of separate experiments, yeast RNA, mixtures of its constituent nucleosides, its constituent bases and ribose were administered orally to rats. In each instance, the resultant changes in the composition of body fluids were monitored using sensitive methods.2. Ingestion of RNA (100g/kg diet) caused detectable increases in intestinal ribose, inorganic phosphate, uridine, pseudouridine, uracil, inosine, uric acid and probably other purine bases. Their accumulation did not detectably affect the rate of passage of food along the digestive tract, even though some nucleosides are known to affect gut motility.3. Although plasma levels of uric acid and uridine were higher when RNA was administered in the diet, these changes were very slight compared with those in plasma uracil, which in some experiments were increased more than 20-fold compared with control levels (300μmol/l). Analysis of erythrocytes indicated that the internal environment of at least some cells of the body are similarly altered.4. Analyses indicated that all dietary RNA-phosphate passed into the urine from the gut but most of the RNA-ribose was probably metabolized. Uracil and uric acid levels in the urine reflected plasma composition.5. The effect of orally administered mixed nucleosides on blood and urine composition was similar to that of RNA, but the response to an equivalent mixture of free bases differed in several respects; cytosine, adenine and hypoxanthine appeared in urine only under these circumstances.

End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen.

“…Renal failure without ESR, however, did not cause elevation of pentosidine in nondiabetic or noninsulin dependent diabetic subjects (Figs. 4 …”

Uridine catabolism in Kupffer cells, endothelial cells, and hepatocytes

“…The pyrimidine nucleoside level in serum has been found independent from dietary RNA supply [3] or food restriction [l] and revealed no diurnal variations [l]. These observations suggested a regulatory mechanism for monitoring blood plasma uridine.…”

“…Our studies suggest a co-operation of Kupffer cells, endothelial cells, and hepatocytes in the breakdown of uridine from portal vein blood with uridine phosphorolysis predominantly occurring in Kupffer cells and with uracil catabolism restricted to parenchymal liver cells.Uridine is present in blood plasma of different species in relatively constant micromolar concentrations [l -51 providing a source for nucleotide synthesis on the salvage pathway [5,6]. The pyrimidine nucleoside level in serum has been found independent from dietary RNA supply [3] or food restriction [l] and revealed no diurnal variations [l]. These observations suggested a regulatory mechanism for monitoring blood plasma uridine.…”

“…Uridine is present in blood plasma of different species in relatively constant micromolar concentrations [l -51 providing a source for nucleotide synthesis on the salvage pathway [5,6]. The pyrimidine nucleoside level in serum has been found independent from dietary RNA supply [3] or food restriction [l] and revealed no diurnal variations [l]. These observations suggested a regulatory mechanism for monitoring blood plasma uridine.…”

“…Kupffer cells demonstrated the highest rate of uridine phosphorolysis. 3 5 min after the addition of the nucleoside the label in uracil amounted to 51%, 13%, and 19% of total radioactivity in the medium of Kupffer cells, endothelial cells, and hepatocytes, respectively. If corrected for Kupffer cell contamination, hepatocyte suspensions demonstrated similar activities as endothelial cells.…”