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Title:Influence of Dietary Arginine Deficiency and Increased Nitrogen Metabolism on the Induction of Orotic Aciduria
Author(s):Hassan, Abdelmonem Sadig
Department / Program:Food Science
Discipline:Food Science
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Health Sciences, Nutrition
Abstract:Arginine deficiency is associated with a dramatic orotic aciduria. Liver slices from rats fed a purified L-amino acid diet with (control) and without arginine supplementation were used for studies of ('14)C-bicarbonate incorporation into orotic acid. The nanomoles of orotic acid synthesized in isolated liver slices from both control and arginine deficient animals increased linearly with time. Orotic acid biosynthesis was significantly greater in liver slices than slices of heart, muscle, kidney, and minced spleen when ammonia was used as a nitrogen source. The order of orotate biosynthesis from ('14)C-bicarbonate was liver > spleen > kidney > muscle > heart. Arginine deficiency resulted in a significant stimulation of liver orotic acid biosynthesis. Orotic acid synthesis from spleens isolated from arginine deficient rats was also enhanced compared with controls. Orotic acid production in liver slices using glutamine as the nitrogen source was also significantly greater in rats fed an arginine deficient diet compared to controls.
The incorporation of {6-('14)C}-orotic acid into RNA was significantly reduced in the arginine deficient rat compared to controls. Additionally, {('32)P}-orthophosphate incorporation into RNA and DNA was significantly depressed in arginine deficient rats. The activities of the pyrimidine enzymes, aspartate transcarbamylase (ATC) and dihydroorotate dehydrogenase (DHODH) were significantly increased in rats fed an arginine deficient diet. ATC and DHODH activities in rats fed the arginine deficient diet returned to control activities after 3 weeks of feeding. Orotidine 5' phosphate decarboxylase and orotate phosphoribosyl transferase activities were not affected by dietary arginine availability. In the rat fed an arginine deficient diet there was an increase in total liver pyrimidine nucleotides and a decrease in the total purine nucleotides. Significant alterations in the individual liver nucleotides were also observed.
In vitro incorporation of {('14)C}-bicarbonate into orotic acid by rat liver slices was used also to study the rate of orotic acid biosynthesis in the presence of physiological and saturation concentrations of ammonium chloride (NH(,4)Cl). The influence of body size on orotic acid synthesis in rats fed purified L-amino acid diets with or without arginine was examined. Orotic acid biosynthesis was significantly greater at both NH(,4)Cl concentrations examined in liver slices obtained from arginine deficient rats for all sizes of rats. A linear decrease in orotic acid synthesis as a function of body size was observed for rats fed either of the diets. The rate of orotic acid biosynthesis was also found to increase linearly in livers from rats fed increasing dietary protein when determined by incubation with physiological concentrations of ammonium chloride. Orotic acid biosynthesis was also found to increase with increase in length of fasting. Alteration in urinary orotic acid and urea confirm these rates of synthesis. These results support the hypothesis that when the urea cycle is overtaxed, carbamyl phosphate synthesized intramitochondrially by carbamyl phosphate synthetase I may be shunted into pyrimidine biosynthesis.
Issue Date:1980
Type:Text
Language:English
Description:174 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1980.
URI:http://hdl.handle.net/2142/77248
Other Identifier(s):(UMI)AAI8026514
Date Available in IDEALS:2015-05-13
Date Deposited:1980


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