Ammonia: Its Effects on Biological Systems, Metabolic Hormones, and Reproduction

Degradation of pyrimidines and pyrimidine analogs--pathways and mutual influences.

The level of N-acetyl-l-glutamate showed a diurnal rhythm, which was associated primarily with dietary ingestion. Since the hepatic level of arginine, activator for acetylglutamate, is one of the plausible principle factors responsible for the regulation of acetylglutamate level, the effect of arginine was further studied. The intraperitoneal administration of a large amount of arginine increased the level of acetylglutamate and the effect was augmented by the combined administration of glutamine. The arginine administration stimulated the hepatic synthesis of acetylglutamate as measured with [14C]glutamate as tracer, but did not affect the half-life (about 20 min) of the synthesized 14C-labeled acetylglutamate.



The effect of arginine in raising the acetyglutamate level was also demonstrated in vitro in isolated rat liver cells. On the other hand, pent-4-enoic acid, known to inhibit fatty acid oxidation and to decrease acetyl-CoA production in the liver, lowered the level of acetylglutamate in the rat liver cells. It was shown that the cellular ureogenic capacity, as measured with NH4Cl as nitrogen source, showed a close correlation with the varying levels of acetylglutamate, brought about by arginine or pent-4-enoic acid.



The carbamoyl phosphate level, which may reflect the balance between its synthesis and utilization for citrulline synthesis, was low (about 1 nmol/g) and remained relatively constant in the livers of intact mice even when the rate of urea synthesis was expected to vary with changes in the dietary protein content. A transient increase in the level was brought about by agents expected to increase the synthesis or to inhibit the utilization, such as ammonia, N-acetylglutamate diethyl ester, or norvaline. These results, together with others, suggest that in intact animals the production of carbamoyl phosphate is coupled to its utilization for citrulline synthesis.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1978.tb12250.x

Role of acetylglutamate in ureotelism. Variations in acetylglutamate level and its possible significance in control of urea synthesis in mammalian liver.

Ammonia metabolism, urea cycle capacity and their biochemical assessment.

Purine and pyrimidine metabolism in parasitic protozoa

Orotic acid biosynthesis in rat liver: studies on the source of carbamoylphosphate.

Regulation of pyrimidine biosynthesis by purine and pyrimidine nucleosides in slices of rat tissue.

1. 1. Evidence for the occurrence of the orotate pathway for the de novo biosynthesis of pyrimidines in the developing sea urchin embryo was provided by the incorporation of (14C) NaHCO3, (14C) carbamoylaspartate, and (6-14C) orotic acid into the pyrimidines of RNA, in vivo. 2. 2. This interpretation was supported by the observation that the radio-label from (14C) NaHCO3 appeared in the C-2 position of the uracil ring and by the demonstration of the activity of all of the enzymes of the orotate pathway in cell-free extracts of sea urchin eggs. 3. 3. Evidence was obtained for the regulation of the de novo pathway by end-product inhibition.

Pyrimidine biosynthesis and its regulation in embryos of the sea urchin, Arbacia punctulata.

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Orotic acid biosynthesis in rat liver: studies on the source of carbamoylphosphate.

Regulation of pyrimidine biosynthesis by purine and pyrimidine nucleosides in slices of rat tissue.

Pyrimidine biosynthesis and its regulation in embryos of the sea urchin, Arbacia punctulata.