Abstract
Experiments were undertaken to investigate the working hypothesis that the liver is a source of pyrimidine nucleotide precursors for utilization by peripheral tissues, that the precursor is orotate, and that the erythrocytes act as an intermediary buffer, and convert the orotate to uridine, which is more readily utilised by peripheral tissues than orotate. Differentiated human hepatoma cells were labelled with 14C aspartic acid and labelled orotate was removed from the medium by selective precipitation techniques. Acid precipitable radioactivity was low in lymphoblasts, fibroblasts or erythrocytes labelled alone with 14C orotate but were enhanced tenfold if erythrocytes were co-cultured with the nucleated cells. Factors influencing orotate metabolism in the erythrocyte include phosphate, bicarbonate and other factors operating in a time dependent manner. Orotate and many pyrimidine nucleotides are directly quantifiable on high pressure liquid chromatography of extracts from lymphoblasts, fibroblasts and erythrocytes and their measurement provide a ready means for diagnosis of inherited disorders of pyrimidine metabolisms such as orotic aciduria and pyrimidine 5′ nucleotidase deficiency.
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Harley, E., Berman, P., Sacks, S. et al. SOURCE AND FATE OF CIRCULATING PYRIMIDINES: 81. Pediatr Res 19, 757 (1985). https://doi.org/10.1203/00006450-198507000-00101
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DOI: https://doi.org/10.1203/00006450-198507000-00101
