The Metabolism and Urinary Excretion of Orotic Acid in Hyperargininaemic Sheep

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Abstract
The synthesis, blood plasma turnover and urinary excretion of the orotic acid in normo- and hyperargininaemic sheep was investigated. The whole-body orotate formation was evaluated indirectly by the measurement of urinary orotate excretion after blockage of pyrimidine pathway with 6-azauridine (4 hour i.v. infusion of 0.2 mg.kg-1.min-1). Simultaneous infusion of L-arginine (2.5 mumols.kg-1.min-1) significantly elevated the blood plasma arginine, ornithine and urea level, however, it did not significantly influence urinary orotate excretion. In normoargininaemia blood plasma turnover of exogenous orotic acid amounted to 4.9 min and 67% of this compound was eliminated through the kidneys. The renal clearance of orotic acid amounted to 21.7 ml.min-1.kg-0.75. Hyperargininaemia elevated blood plasma turnover to 8.2 min, and diminished the renal clearance of this metabolite to 13.7 ml.min-1.kg-0.75. These results indicate that hyperargininaemia and hyperornithinaemia do not change the whole body synthesis of orotic acid in sheep but they can affect renal excretion of this metabolite, particularly at the rate of tubular secretion close to saturation.