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At least 883 records · Page 49Linked to original sources
PubMed1978

Elevation of the salvage synthesis of ribonucleic acid in the rat liver during the induction of hepatoma with 3'-methyl-4-(dimethylamino)azobenzene.

Incorporation of uracil and orotic acid into the ribonucleic acid (RNA) fraction of rat liver during carcinogenesis induced with 3'-methyl-4-(dimethylamino)azobenzene was investigated. Uracil incorporation was found to be gradually elevated during the early stage (about 2 weeks) of the carcinogenesis, although not in the normal rat liver homogenates contacted with the carcinogen for a short hours, and the elevated uptake was maintained until tumor induction. On the other hand, orotic acid incorporation reverted to the original level after a temporary increase during the early stage. In a good agreement with the increased uracil incorporation, activities of both uridine phosphorylase and uridine kinase involved in the salvage pathway of RNA synthesis also increased during the early stage, and their activities in the liver were maintained at elevated levels after discontinuance of the carcinogen feeding. The activity of uridine monophosphate (UMP) pyrophosphorylase, converting uracil to UMP, was not detected during the early stage. Significance of the activation of the salvage pathway of RNA synthesis during the early stage of an axo dye-induced carcinogenesis were discussed.

Animals↗
PubMedDate not supplied

[Destiny of 5-methylcystosine of newly synthesized DNA fraction in bone marrow cells].

Methylation kinetics of newly formed DNA in bone marrow cell culture of animals and healthy humans was studied in order to investigate the role of DNA methylation in proliferation and differentiation of hematopoietic cells. Synthesis of a DNA fraction with extremely high cytosine methylation level was observed under the incubation of cells with 14C-orotic acid for 0.5-1 hour. Long-term incubation (3 and more hours) with 14C-orotic acid resulted in a rapid decrease of 5-methylcytosine radioactivity and in an increase of thymine radioactivity. Elimination of 14C-orotate from the medium and inhibition of DNA synthesis with hydroxyurea did not change kinetics of the radioactivity content in 5-methylcytosine and thymine in newly synthesized DNA. No synthesis of hypermethylated DNA fraction was observed under incubation of cells with preformed pyrimidine precursors.

Animals↗
PubMedDate not supplied

[The assimilation by Eimeria tenella coccidia of DNA and RNA precursors from the host cell].

The assimilation of purine and pyrimidine bases, their nucleosides and orotic acid from the host cell by coccidian E. tenella was studied by means of radioactive precursors of DNA and RNA. It has been established that within their development and reproduction the parasites use selectively different precursors of DNA and RNA from the host cell. Coccidians use intensively the purine base 14C-adenine, assimilate negligibly the pyrimidine base 14C-uracil and nucleoside 14C-uridine and do not use at all 14C-thymidine and 14C-thymine. The coccidians were found to assimilate most intensively 14C-orotic acid, the lower precursor of pyrimidine bases.

Animals↗
PubMed1969

Isolation of chick intestinal nuclei. Effect of vitamin D3 on nuclear metabolism.

1. Chick intestinal nuclei were isolated, with practically no contamination from other organelles and whole cells, by centrifugation through 2.4m-sucrose. 2. The proportions of RNA, DNA and protein of the isolated nuclei were unaffected by the vitamin D status of the birds. The RNA/DNA ratio was 0.15. 3. The incorporation of [5-(3)H]orotic acid into the rapidly labelled intestinal nuclear RNA, after a 10min. pulse of the orotic acid, was increased in vitamin D-deficient chicks only 10min. after a 125mug. dose of cholecalciferol. 4. There was no stimulation of the DNA-dependent RNA polymerase activity of the isolated nuclei from birds treated with cholecalciferol. 5. The results are discussed in relation to the changes occurring during the lag period, after administration of cholecalciferol and before Ca(2+) transport is detected, and the function of the vitamin.

Animals↗
PubMed1975

[Problems associated with the labelling of RNA with radioactive precursors in vivo (author's transl)].

The radioactivity of RNA, DNA and proteins in the liver, muscles and cerebrum of 30-day-old rats after labelling with [3H]uridine, [14C]uridine, [3H]cytidine or [3H]orotic acid was measured. It was found that after administration of [3H]uridine, the proteins were 5 - 10 times more radioactive than the RNA. After administration of [14C]uridine, the proteins were 1 - 2 times more heavily labelled than the RNA. Hydrolysis of the proteins followed by chromatography of the amino acids revealed that the protein labelling was mostly due to [3H]glutamate. In the liver, [3H]orotic acid produced very specific labelling of the RNA. The radioactivity of the proteins is very slight. However, the specific labelling of the RNA in the muscles and cerebrum is not so pronounced with this precursor. [3H]Cytidine is an ideal precursor for RNA. The labelling of protein in all three organs examined is very slight, and furthermore, the specific activity of the RNA is 10 - 20 times higher than after labelling with uridine. We were also able to show that after labelling with radioactive uridine, the method of isolation of RNA by alkaline hydrolysis gives incorrect results, because [3H]amino acids interfere with the measurement of the specific activity of the RNA. The heavy labelling of proteins by [3H]-uridine must also be taken into account in histoautoradiography, because our experiments showed that in liver, the proteins in the cell nucleus are 3 times as radioactive as the nucleic acids. The particulate components of the cytoplasm are even 20 times more radioactive than the nucleic acids.

Animals↗
PubMed1982

Intestinal very low density lipoprotein secretion in rats fed various amounts of fat.

1. The effect of a high-fat diet (30% fat by wt.) on intestinal very low density lipoprotein (VLDL) secretion was studied in male rats after specific inhibition of hepatic VLDL secretion by dietary orotic acid. Total VLDL secretion (from liver and intestine) was measured in animals not receiving orotic acid. 2. Fat-feeding resulted in a 32% decreased post-Triton secretion of total serum VLDL triacylglycerols as compared to a control (low fat) diet. Concomitantly, a large stimulation of post-Triton intestinal VLDL triacylglycerols secretion was measured in fat-fed rats. Thus, the major part (64%) of circulating triacylglycerols transported as VLDL originated from the intestine in these animals, leading presumably to an increased secretion of intestinal apolipoproteins. 3. Intestinal VLDL and chylomicron secretion rates increased with the amount of fat in the diet (7, 13, 20 or 30% fat by wt.). Whereas the chylomicron secretion was linearly related to the dietary fat content, the relationship between intestinal VLDL secretion and fat content of the diet was sigmoidal. The highest stimulation of intestinal VLDL formation was observed within a narrow range of dietary fat content (between 10 and 20%).

Animals↗
PubMed1978

Liver lipid alterations in rats fed arginine deficient diets.

Arginine deficiency is associated with a marked increase in liver lipids in the rat. Triglyceride accumulation accounts for most of the fatty infiltration. Cholesterol concentration per gram of liver increased approximately 280% above control rats receiving dietary arginine. The percentage of phospholipids was significantly decreased in the arginine-deficient rat liver compared to controls. The fatty acid composition revealed a significant reduction in the reduction in the percentage of palmitic, palmitoleic, oleic, and linoleic acids. However, both stearic and arachidonic acids were increased approximately 250 and 160%, respectively, in arginine-deficient livers compared to controls. Arginine deficiency in the rat causes a marked alteration in lipid metabolism similar to that observed with orotic acid feeding. The similarities or arginine deficiency and orotic acid feeding are discussed.

Animals↗
PubMed1983

The modulating effect of an inhibitor of cholesterolgenesis present in bovine milk upon the synthesis of cholesterol, dolichol and ubiquinone.

Bovine milk contains two inhibitors of hepatic cholesterol genesis. One of these, identified as orotic acid, influences the early segment of the cholesterol biosynthetic pathway and suppresses the conversion of acetate to mevalonate. In this study the other inhibitor was shown to curtail the formation of compounds past farnesyl pyrophosphate on the squalene-cholesterol branch of the pathway. Thus cholesterol synthesis may be suppressed while the production of two other products of the branched pathway, dolichol and ubiquinone, is allowed to continue. The possible role of these ingested regulators in the metabolism of the young until they achieve sufficient development is discussed.

Acetates↗
PubMed1989

Ornithine aminotransferase activity, liver ornithine concentration and acute ammonia intoxication.

5-Fluoromethylornithine (5FMOrn) is a specific inactivator of L-ornithine:2-oxoacid aminotransferase (OAT). Inactivation of OAT causes the enhancement of L-ornithine (Orn) concentrations in all tissues. Intraperitoneal or oral administration of 10-50 mg/kg of 5FMOrn per day to albino mice rendered partial protection against lethal intoxication with 26 mmol/kg of ammonium acetate. The protective effect was maximal around 16 h after 5FMOrn administration, at the time when endogenous Orn concentrations were maximal. At this time protection by 5FMOrn against acute ammonia intoxication was comparable to that observed 1 h after the intraperitoneal administration of 10 mmol/kg of L-arginine. Pretreatment with 5FMOrn prevented the enhancement of excessive urinary excretion of orotic acid by ammonia intoxicated mice, and it enhanced urea formation in the liver. These biochemical effects demonstrate that 5FMOrn shifts Orn into the urea cycle, Orn which normally would be transaminated. Since even long-term treatment of mice with 5FMOrn did not reveal toxic effects, this compound may be considered for the treatment of certain conditional deficiencies of Orn or arginine.

Acetates↗
PubMed2003

Influence of dietary arginine on sexual dimorphism of arginine metabolism in mice.

We have studied the influence of dietary arginine on tissue arginine content, and arginine metabolism in CD1 mice. Dietary arginine restriction produced by feeding mice with a low arginine diet (0.06%) produced a marked decrease in arginine concentrations in the plasma, skeletal muscle and kidney of female mice (72%, 67% and 54%, respectively) while in male mice the decreases were smaller (58% in blood and 18% in the skeletal muscle). This diet abolished not only the sexual dimorphism in arginine content observed in mice fed with the diet containing 1% arginine, but also reduced renal activities of arginase and nitric oxide synthase in the female mice and ornithine decarboxylase and the decarboxylation of arginine in the male mice. Urinary putrescine excretion was dramatically reduced by arginine restriction in the male mice whereas orotic acid excretion increased about 30 fold in both sexes; urea and creatinine excretion did not change. Taken together our results indicate that dietary arginine plays a relevant role in the maintenance of the sexual dimorphism in arginine content and arginine metabolism in CD1 mice, and that this may have physiological significance because of the important effects that arginine-derived products exert on a variety of cellular processes.

Animals↗
PubMed2000

[Course of the progression of experimentally induced arteriosclerotic vessel wall changes after treatment with magnesium orotate] .

There are some experimental and clinical results regarding blood vessel protective properties of magnesium orotate (CAS 27067-77-2) till now. The goal of the present investigation was to verify the therapeutical efficacy of magnesium orotate vs. its singular components in cholesterol fed rabbits. Besides, the blood-lipid concentrations (LDL as risk factor for atherosclerosis and HDL as negative risk factor) were analyzed in relation to pathomorphological changes in the aortic blood vessel wall. The results of our experiments in New Zealand rabbits support the assumption that orotic acid and especially magnesium orotate influence the lipid level and/or the LDL/HDL-quotient in a favorable way and that they decrease the interaction between monocytes/macrophages and the endothelium of the blood vessels. Consequently, the plaque formation will be decreased in a clinically relevant manner.

Animals↗
PubMed1984

Effect of hydrocortisone on the expression of mitochondrial genes in the liver of normal and alloxan diabetic rats.

The incorporation of 14C-orotic acid into mitochondrial RNA from the liver of alloxan diabetic (AD) rats was increased after a single or repeated administration of hydrocortisone (HC; 5 mg kg-1). while the increase in normal animals was much less. The activity of RNA-polymerase in isolated mitochondria was also considerably increased in AD rats after HC administration, but this was not related to any changes of mitochondrial membrane permeability for precursors. Electrophoretic analysis of total and poly(A)-containing RNA did not show any substantial changes in liver mitochondrial RNA of AD rats treated with HC. No changes in the transcription of liver mitochondrial DNA from intact, AD or AD plus HC treated rats were found after the hybridization of mitochondrial RNA with a rat mitochondrial DNA or DNA from recombinant plasmids, containing inserts of restriction fragments of mitochondrial DNA. In addition, an increase in the rate of protein synthesis was observed after a repeated administration of HC to intact animals, while that in AD rats was decreased and started to increase only after a single administration of HC. In contrast, after a repeated administration of HC the rate of protein synthesis was decreased. It was concluded that the mechanism of RNA and protein biosynthesis in liver mitochondria of AD rats is much more sensitive to the action of glucocorticoids as compared to intact animals and that the biosynthesis of all populations of mitochondrial RNA in the liver of AD rats is increased after HC treatment in a similar degree, the quality of mitochondrial gene expression being not changed.

Animals↗
PubMed1978

[Replication and reassociation kinetics of nuclear matrix DNA from regenerating rat liver].

Fraction 1, containing 65--70% of nuclear DNA (nDNA) was extracted from isolated rat liver nuclei. Then nuclear matrix fraction, containing 30--35% of nDNA was extracted with 1.2 M NaCl. About 1% of nDNA war discovered in residual matrix. Specific activity of residual matrix labelled DNA within 1 and 3 min. after the injection of 14C-orotic acid into the liver portal vein (24 hours after hepatectomy) was respectively in 70 and 50 times higher, and that of matrix DNA--in 45 and 20 times as high as in fraction 1 DNA. Thus, replication begins from nuclear matrix DNA. The latter is enriched with unique sequences by 10%, as compared with total nDNA, and its reassociation kinetics does not change at different stages of the cell cycle (0 and 24 hours after partial hepatectomy). It is suggested, that DNA does not migrate with respect to nuclear matrix under replication.

Animals↗
PubMed2001

Large-scale production of the carbohydrate portion of the sialyl-Tn epitope, alpha-Neup5Ac-(2-->6)-D-GalpNAc, through bacterial coupling.

Alpha-Neup5Ac-(2-->6)-D-GalpNAc, the carbohydrate portion of sialyl-Tn epitope of the tumor-associated carbohydrate antigen, was prepared by a whole-cell reaction through the combination of recombinant Escherichia coli strains and Corynebacterium ammoniagenes. Two recombinant E. coli strains overexpressed the CMP-Neup5Ac biosynthetic genes and the alpha-(2-->6)-sialyltransferase gene of Photobacterium damsela. C. ammoniagenes contributed to the production of UTP from orotic acid. Alpha-Neup5Ac-(2-->6)-D-GalpNAc was accumulated at 87 mM (45 g/L) after a 25-h reaction starting from orotic acid, N-acetylneuraminic acid, and 2-acetamide-2-deoxy-D-galactose.

Acetylgalactosamine↗
PubMed1979

Alterations in metabolism of cytidine components in rat liver after oral administration of butylated hydroxytoluene (in vivo study).

The administration of the antioxidant, butylated hydroxytoluene (BHT) to rats decreased the utilization of [2-14C]orotic acid for the synthesis of cytidine nucleotides in the acid-soluble extract and RNA of the liver. The specific activity of the uridine components was slightly decreased. The depression of the specific activity of the cytidine components depended on the dose of the drug. Simultaneously preformed [U-14C]cytidine in experimental rats was to a higher degree transported to the liver and incorporated into RNA cytosine; its deamination was markedly suppressed. Both phenomena depend on the BHT dose. The concentration of both the uridine and the cytidine components of the acid-soluble extract remained unaffected by the administration of BHT. The utilization of [2-14C]orotic acid for the synthesis of DNA cytosine was depressed after the administration of BHT; by contrast, the specific activity of DNA thymine was higher. The incorporation of [1-14C]palmitic acid into microsomal phospholipids was not substantially influenced over the dose range 25--500 mg BHT/kg. The specific activity of neutral lipids in microsomes increased.

Animals↗
PubMed1989

Selective activity of 5-fluoroorotic acid against Plasmodium falciparum in vitro.

Unlike mammalian cells, malarial parasites are completely dependent on de novo pyrimidine metabolism. Even though these parasites do not use external uracil or uridine, orotic acid, an intermediate of pyrimidine biosynthesis, is successfully transported into the parasite and incorporated into parasite nucleic acids. On this basis, it was hypothesized that 5-fluoroorotate, a cytotoxic derivative of orotic acid, may be a potent and selective antimalarial agent. In vitro, 5-fluoroorotate caused 50% inhibition of the growth of Plasmodium falciparum at a concentration of 6.0 nM. In contrast, 5-fluorouracil, 5-fluorouridine, and 5-fluoro 2'-deoxyuridine were much less effective against malarial parasites. Chloroquine-susceptible and chloroquine-resistant clones of P. falciparum were equally susceptible to 5-fluoroorotate. The toxicity of 5-fluoroorotate was evaluated on four human cell lines (HT-1080, IMR-90, HeLa S3, and HL-60) and one mouse cell line (L-1210). Compared with malarial parasites, the mammalian cells were relatively tolerant of 5-fluoroorotic acid (50% inhibitory concentration, 0.9 to 10 microM). Finally, in the presence of 1 mM uridine, all mammalian cells were partially protected from 5-fluoroorotate cytotoxicity, but uridine offered no protection to P. falciparum.

Animals↗
PubMed1983

Capacity of rat liver for pyrimidine synthesis and catabolism during fetal and neonatal development.

The capacity of minces of rat liver to synthesize and degrade pyrimidines during fetal and neonatal development was examined. Pyrimidine synthesis was determined by measuring the rate of incorporation of NaH14CO3 into orotic acid. Pyrimidine catabolism was estimated by measuring the generation of 14CO2 from [2-14C]uridine. The incorporation of [2-14C]uridine into RNA was determined simultaneously with measurements of uridine catabolism. The activity of beta-ureidopropionase, the enzyme which catalyzes the terminal reaction in the dihydropyrimidine catabolic pathway, was also monitored in cell-free extracts of liver throughout the perinatal period. Catabolic activity was detected at the earliest stage of gestation examined (16 days) and rose sharply during fetal development to reach adult levels at birth or shortly thereafter. A similar rise in the activity of beta-ureidopropionase was somewhat delayed when compared with the rise in overall catabolic activity; the enzyme activity at birth was about half the adult level. By way of contrast, the incorporation of NaH14CO3 into orotic acid and [2-14C]uridine into RNA were highest in 16-day fetal liver and declined sharply with fetal and neonatal development. These results demonstrate an appreciable capacity for pyrimidine catabolism in fetal liver, and also contribute to growing evidence that fetal tissues are capable of meeting their pyrimidine requirements through de novo synthesis. The contrast observed between the rate of synthesis of orotic acid and the capacity for pyrimidine degradation throughout perinatal development fits the pattern which has emerged from other studies showing the pathways for the anabolism and catabolism of pyrimidines to be regulated inversely to one another.

Aging↗
PubMed1964

EFFECTS OF BICARBONATE ON GROWTH OF PASTEURELLA PESTIS. 3. REPLACEMENT OF BICARBONATE BY PYRIMIDINES.

Baugh, C. L. (Fort Detrick, Frederick, Md.), A. W. Andrews, and M. J. Surgalla. Effects of bicarbonate on growth of Pasteurella pestis. III. Replacement of bicarbonate by pyrimidines. J. Bacteriol. 88:1394-1398. 1964.-The effect of carbon dioxide on the growth of virulent Pasteurella pestis cultures at 37 C with aeration was studied by substituting known products of carbon dioxide fixation for bicarbonate in the test system. The growth of the virulent cells in the inoculum is stimulated and the culture remains virulent, if bicarbonate is replaced by orotic acid. The addition of cytosine, uracil, or citrulline also results in the retention of virulence, but the effect on the growth of the virulent cells is not as pronounced as with bicarbonate or orotic acid. It is proposed that an impaired pyrimidine synthesis due to a deficiency in carbomyl phosphate is responsible for the loss of virulence by P. pestis in aerated broth cultures at 37 C. The carbamyl phosphate deficiency may be enhanced by the loss of metabolically produced carbon dioxide at 37 C.

Arginine↗