[Effects of potassium orotate on various pentose fractions in the blood of normal individuals].
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The effect of hydrocortisone on the biosynthesis of mitochondrial and cytoplasmic RNA in the liver of adrenalectomized rats was studied. A biphasic effect of hydrocortisone on the induction of RNA biosynthesis was observed: a short-term increase at 10th and 90th minute and more prolonged increase with a maximum at 210 min. At the same the intramitochondrial pool of labelled precursors of RNA did not change. According to hybridization data the expression of mitochondrial URF 5 and 6 genes linked to the effect of glucocorticoids was selectively increased already at the initial stage of hormone effect, but the resulting remarkable increase of RNA biosynthesis did not further result in changes of the spectrum of mitochondrial RNA. Specific activity of cytoplasmic RNA was decreasing at 10 min and increasing at 1, 2 and 4 h after the administration of hydrocortisone. The size of cytoplasmic acid soluble pool of labelled RNA precursors was increased only at 4 h after the administration of the hormone. It seems that a decrease of specific activity of cytoplasmic RNA during the initial period of hormone action may result from the changes of RNA transport from the nuclei to the cytoplasm.
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In the spleen, thymus and liver of mice and rats carrying transplantable rapidly growing hepatomas a shift between the de novo and "salvage" pathways of the pyrimidine RNA nucleotides synthesis in favour of the de novo one was observed. The phenomenon was found to be the manifestation of a drastically diminished uridine utilization by the host tissues, this precursor being preferentially and avidly used by the tumour for its own RNA synthesis. The above findings are regarded as the result of a successful competition of the tumour with the host tissues for vital metabolites representing one of the forms of the systemic effects of malignant neoplasms.
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Experiments with 45-75-g male rats gave conclusive evidence that the simultaneous absence from the diet of arginine, ornithine, or citrulline caused an immediate and persistent elevation of orotic and citric acids in the urine. The experiments also demonstrated that a deficiency of no other individual amino acid increased urinary citrate and orotate. Elevated urinary excretion of orotic and citric acid occurred independently of the form of nonessential nitrogen. Replacement of arginine isonitrogenously with ornithine or citrulline prevented the rise in urinary orotic acid, but had different effects on growth, urinary citrate, and urinary urea. These differences were probably due to differential uptake of arginine, ornithine, and citrulline by tissues; In the reported experiments employing L-amino acids as sources of dietary nitrogen, a deficiency of any amino acid indispensable for growth and nitrogen balance or a deficiency of arginine, ornithine, or citrulline retarded growth, increased urinary urea, and decreased urinary ammonia. It is concluded that the severe loss of orotic acid during urea-cycle amino acid deficiency arises from a decreased capacity of the urea cycle to detoxify ammonia, thereby causing increased shunting of intramitochondrial carbamyl phosphate into pyrimidine synthesis. The similarities in metabolism during arginine deficiency and ammonia intoxication are discussed. The evidence shows that urinary orotic acid may be a valuable measure of arginine nutrition in mammals.
Sodium fluoride inhibits an increase of nucleic acids in the cells nuclei of the rat liver after a partial resection of this organ. Introduction of thymidine to the animals poisoned with sodium fluoride, contrary to glutamine and orotate, causes a sharp decrease in the amount of nuclei in 1 mg of tissue and normalization of the nucleic acid content in them. Changes in the mitotic activity may be connected with a disturbance in the normal ratio of the nucleic acids synthesis precursors.
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