Abnormal orotic acid metabolism associated with acute hyperammonaemia in the rat

Add time:08/10/2019    Source:sciencedirect.com

The effect of acute ammonium acetate intoxication upon orotic acid-6-14C urinary excretion, distribution between blood and liver, and its incorporation into acid-soluble liver nucleotides, was studied in rats.Increased urinary orotic acid excretion was demonstrated following ammonium acetate treatment.In the first series of experiments, the rats pretreated with ammonium acetate were sacrificed at various time intervals after 14C-OA injection ranging from 1 to 60 min. The radioactivity content of the acid-soluble liver fraction 30–60 min following ammonium acetate treatment showed values lower by a factor of 1.5-2 when compared with saline or sodiumacetate-treated controls. The clearance of the label from blood was slower than in controls.In vivo, 14C-OA conversion to uracil nucleotides in the liver was decreased, falling to 50% 15 min after ammonium acetate treatment. In control animals 1 min after orotic acid injection, all the radioactivity recovered from the acid-soluble liver fraction was in the form of uracil nucleotides (100% conversion).In the second series of experiments, the rats were injected with ammonium acetate followed by 14C-OA at various time intervals from 1 min to 3 hr and sacrificed 5 min later. The most marked decrease in the liver radioactivity content was reached 20 min following ammonium acetate injection.The highest degree of 14C-OA accumulation in the acid-soluble liver fraction was shown 20 min after ammonium acetate treatment. A transient accumulation of endogenously produced orotic acid in the livers of rats treated with ammonium acetate was demonstrated.The rats treated with ammonium acetate showed a twofold increase in the liver acid-soluble uracil nucleotide content.The effect of acute ammonia intoxication on orotic acid formation and disposal is discussed.

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