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At least 199 records · Page 11Linked to original sources
PubMed1994

Determination of orotic acid in serum by high-performance liquid chromatography.

A simple method for the determination of orotic acid in serum is described. The analyses were carried out using a strong anion-exchange column. Orotic acid was separated isocratically with 0.8 M formic acid (pH 2.8, adjusted with 10 M NaOH)-methanol (65:35, v/v) at a flow-rate of 1.0 ml/min. Absorbance at 275 nm was recorded for quantification. Validation yielded a detection limit of 0.07 micrograms/ml and a quantification limit of 0.25 micrograms/ml. The maximum within-day and day-to-day coefficients of variation were less than 6%. The method has the advantage that samples can be easily prepared.

Chromatography, High Pressure Liquid↗
PubMed1975

[Influence of orotic acid upon post-excitatory facilitation released by stimulation of the tooth pulp].

The influence of orotic acid on post-excitatory facilitation of evoked potentials released by electric stimulation of the tooth pulp in the sensomotor cortex was studied. 15-360 min following application of 100 mg/kg orotic acid, increase in amplitude of potentials released by stimulation of the tooth pulp, reinforcement of the post-excitatory facilitation observable 5 msec after stimulation occurred.

Animals↗
PubMed1997

High-performance liquid chromatographic determination of orotic acid as its methyl derivative in human urine.

Described is a method for the determination of orotic acid as its methyl ester in human urine. The method involves the use of solid-phase extraction to isolate pyrimidines from urine and derivatization with methanol and sulfuric acid, followed by isocratic high-performance liquid chromatography on a reversed-phase C18 column with UV absorbance detection. The assay is shown to be sufficiently sensitive for use in clinical investigations where elevated orotic acid excretion is suspected.

Adult↗
PubMedDate not supplied

Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid.

OBJECTIVE: We compared the effect of dietary phosphatidylcholine (PC) with that of triacylglycerol (TG), both with the same fatty acid profiles, on fatty infiltration in orotic acid (OA)-induced fatty liver of Sprague-Dawley rats. METHODS: Rats were fed an OA-supplemented diets containing TG (TG+OA group) or PC (20% of dietary lipid, PC+OA group) for 10 d. Rats fed the TG diet without OA supplementation served as the basal group. RESULTS: Administering OA significantly increased the weights and TG accumulation in livers of the TG+OA group compared with the basal group. These changes were attributed to significant increases in the activities of fatty acid synthase, malic enzyme, and glucose-6-phosphate dehydrogenase, which are fatty acid synthetic enzymes, and phosphatidate phosphohydrolase, a rate-limiting enzyme of TG synthesis. However, the PC+OA group did not show TG accumulation and OA-induced increases of these enzyme activities. Further, a significant increase in the activity of carnitine palmitoyl transferase, a rate-limiting enzyme of fatty acid beta-oxidation, was found in the PC+OA group. CONCLUSIONS: Dietary PC appears to alleviate the OA-induced hepatic steatosis and hepatomegaly, mainly through the attenuation of hepatic TG synthesis and enhancement of fatty acid beta-oxidation in Sprague-Dawley rats.

Animals↗
PubMed1990

Studies on the effect of dietary orotic acid on mouse liver carcinogenesis induced by diethylnitrosamine.

The present study was designed to determine whether orotic acid, a liver tumor promoter in the rat, also promotes liver carcinogenesis in the mouse. Eight-week-old male BALB/c mice were initiated with diethylnitrosamine (90 mg/kg i.p.). One week later they were divided into 2 groups and given either a basal diet or the basal diet containing 1% orotic acid (OA). They were killed at 6 or 10 months after the administration of the carcinogen. At 6 months, no nodular lesions were seen in mice whether or not they were exposed to OA. However by 10 months 100% of mice in both groups developed hepatic nodules. OA neither shortened the latent period for the appearance of the nodular lesions not did it increase the size of the nodules. Although BALB/c mice exhibited an increase in uridine nucleotides and a decrease in adenosine nucleotides in the liver upon exposure to OA, the magnitude of the change was less compared with that seen in the rat liver. The resistance of BALB/c mouse to the tumor-promoting effects of OA may reflect in part the resistance of the mouse to OA-induced nucleotide pool imbalance.

Animals↗
PubMedDate not supplied

[Dynamics of orotic acid metabolism in chick tissues].

The processes of pyrimidine nucleotides metabolism were analyzed in cells of chicken small intestine mucosa using the kinetic series-parallel model of the first order equations. The rate constants are calculated for absorption of [2-14C]orotic acid by mucosa cells, its accumulation in blood anc conversion to uridine nucleotides. Stages of uridine nucleotides conversion to cytidine ones and their incorporation into RNA are not described by the system of the first order equations based on the series-parallel model with the single-channel utilization of orotic acid through the pyrimidine pathway. The model into two pathways of free nucleotides metabolism and two individual flows of precursors into RNA corresponds qualitatively to the obtained experimental data. Metabolism of orotic acid along two separate channels might be typical of the chicken liver.

Animals↗
PubMed1990

Prebiotic synthesis of orotic acid parallel to the biosynthetic pathway.

By heating an aqueous solution of aspartic acid and urea, carbamylaspartic acid is first formed and then the molecule is cyclized to dihydroorotic acid (DHO) with loss of water. Irradiation of an aqueous solution of DHO with a tungsten lamp yields orotic acid by photo-dehydrogenation of the molecule. This pathway of orotic acid formation is quite similar to that of biosynthesis of the molecule.

Aspartic Acid↗
PubMed1998

Effect of orotic acid on the metabolism of cerebral cortical astrocytes during hypoxia and reoxygenation: an NMR spectroscopy study.

Astrocytes were incubated under normoxic or hypoxic conditions in Dulbecco's minimum essential medium containing [2-13C]acetate, unlabeled glucose and in some cases orotic acid, an intermediate in pyrimidine biosynthesis. After 12 hr the medium was replaced by fresh medium without drug and incubation was continued for 17 hr in a normal oxygen atmosphere (reoxygenation). Thereafter, medium was removed, cell extracts were prepared, and metabolism in the treatment group was compared to the untreated hypoxia group and to control. 13C and 1H NMR spectra revealed that 13C enrichment in citrate and glutamine C-4 in the initial medium were increased in the presence of orotic acid, compared to the untreated hypoxia group but lower than control. The drug increased acetate utilization during hypoxia to normoxic levels. Thus it appears that the treatment group had a more active mitochondrial metabolism, which was also reflected in higher intracellular uridine diphosphoryl sugars and ADP concentrations. Glutamine labeling was increased in the cell extracts in the presence of orotic acid. Thus it appears that, in the presence of the pyrimidine nucleotide precursor, astrocytes are capable of normal metabolism during hypoxia which might have implications for neuronal survival during low oxygen insults, since neurons are dependent on astrocyte produced precursors for their neurotransmitter synthesis.

Animals↗
PubMed1997

Construction of a plasmid carrying both CTP synthetase and a fused gene formed from cholinephosphate cytidylyltransferase and choline kinase genes and its application to industrial CDP-choline production: enzymatic production of CDP-choline from orotic acid (Part II).

A new method for enzymatic production of cytidine diphosphate choline (CDP-choline) from orotic acid and choline chloride was developed. To establish an industrial manufacturing process, we constructed a plasmid, pCKG55, which simultaneously expressed in Escherichia coli the three following enzymes; CTP synthetase (encoded by the pyrG gene from E. coli), cholinephosphate cytidylyltransferase (encoded by the CCT gene from Saccharomyces cerevisiae), and choline kinase (encoded by the CKI gene from S. cerevisiae). CCT and CKI genes on pCKG55 were designed to be expressed as a single CCT/CKI fused protein. This CCT/CKI fused protein retained both activities and the thermal stability of its cholinephosphate cytidylyltransferase activity was nearly the same as the native CCT enzyme. Corynebacterium ammoniagenes KY13505 and E. coli MM294/pCKG55 were cultured in 5-liter jar fermentor independently. Equal volumes of each broth were mixed in a 2-liter jar fermentor, and then the enzymatic reaction was done using 47 mM orotic acid and 60 mM choline chloride as substrates. After 23 h of the reaction at 32 degrees C, 21.5 mM (11 g/liter) of CDP-choline was accumulated.

Adenosine Triphosphate↗
PubMed1995

An in vivo 31P magnetic resonance spectroscopy study of uridine excess in rats fed orotic acid.

Spatially localized 31P NMR spectroscopy was used to assay in vivo the liver of intact rats fed orotic acid (OA) in a diet which produces hepatic steatosis. Twenty-three sets of multiple volume spectra were obtained from twenty-one 265- to 315-g female rats after 0-9 days of feeding either a 1% OA/64% sucrose diet (12 rats) or a 65% sucrose control diet (9 rats). The intensity of the in vivo diphosphodiester resonance ascribed to UDP-hexos(amin)es increased and the phosphomonoester resonance decreased in intensity prior to fatty infiltration. High resolution NMR spectroscopy of extracts of these livers indicated that the UDP-hexos(amin)e peak included four different UDP-sugars including UDP-N-acetylglucosamine (UDP-glcNAc), and that lower phosphocholine (P-Cho) accounted for the lower phosphomonoester resonance in vivo. Increased UDP-glcNAc is thought to reflect impaired lipoprotein glycosylation as a mechanism for hepatic steatosis in orotic acid feeding. P-Cho deficiency has been shown to be due to an increased rate of phosphatidylcholine synthesis. Low P-Cho concentration has been shown to be associated with lipid accumulation in a choline-deficient diet, but was not previously associated with hepatic steatosis in OA feeding. Changes in phosphorus metabolites were observed 2 days prior to development of fatty liver. HPLC assay of uridine nucleotides showed a good correlation between magnetic resonance spectroscopy and HPLC quantitation. In this study there were two biochemical correlates of impaired hepatic lipid secretion detectable by in vivo assay with 31P NMR spectroscopy. This method has application for noninvasive assays in ornithine transcarbamylase-deficient patients.

Animals↗
PubMed1983

Hormonal stimulation of 3H-orotic acid incorporation into RNA by serum-free cultured hepatocytes.

Insulin and dexamethasone greatly stimulate the incorporation of 3H-orotic acid into RNA. Such a stimulation is associated to an increase in the uptake of the labelled precursor into the acid soluble fraction as well as in the the specific radioactivity of the nucleoside plus nucleotide pool suggesting that hormone supplementation does not affect RNA synthesis by cultured cells. The lack of effect of insulin and dexamethasone on the level of total RNA polymerase activity in nuclei isolated from cultured hepatocytes is in line with this assumption. The hormone stimulated uptake of orotic acid is dependent on protein synthesis since it is completely abolished by cycloheximide.

Animals↗
PubMed1998

Significance of the 5-phosphoribosyl-1-pyrophosphate pool for cardiac purine and pyrimidine nucleotide synthesis: studies with ribose, adenine, inosine, and orotic acid in rats.

Several experimental approaches have been applied to examine the significance of the available pool of 5-phosphoribosyl-1-pyrophosphate (PRPP) for purine and pyrimidine nucleotide metabolism in the rat heart. In a series of studies including some pentoses and pentitols, in particular ribose, it was shown that these sugars were all capable of elevating the cardiac PRPP pool and stimulating the rate of adenine nucleotide biosynthesis. In several pathophysiological situations that were characterized by a decrease in ATP content, the increase in adenine nucleotide biosynthesis elicited by ribose was of such magnitude that the ATP level was replenished partially or completely in a considerably shorter period of time than that without any intervention. In two experimental models, in cardiac hypertrophy induced by aortic constriction with additional isoproterenol administration and in the noninfarcted rat heart after permanent coronary artery ligation, there was also an improvement in global heart function under the influence of ribose. The myocardial cell damage induced by isoproterenol was prevented by ribose. Combination of ribose with adenine or inosine led to an even quicker ATP normalization in the isoproterenol-stimulated rat heart than with either intervention alone. Ribose had no functional effects on the cardiovascular system, whereas adenine, inosine, and orotic acid were demonstrated to have different hemodynamic influences. Adenine and inosine had negative chronotropic and inotropic effects in the intact rat, whereas orotic acid had a positive influence both on the left and right rat heart. On the basis of these experimental studies, a new therapeutic strategy is suggested in which elevation of the available PRPP plays a key role. Once this has been elevated by ribose, additional substrates, such as adenine, inosine, and orotic acids, should be included. This would exploit the full potential of a therapeutic approach that corrects a natural metabolic deficiency of the heart that is the low capacity of the oxidative pentose phosphate pathway in which PRPP is generated.

Adenine↗
PubMed1997

Cardioprotection by orotic acid: metabolism and mechanism of action.

The pyrimidine base, orotic acid (OA), improves the function of recently infarcted hearts subjected to global ischemia but its mechanism of action is unclear. Our aims were to examine (i) in normal rats, the effect of OA on pyrimidine levels in plasma, liver and heart; (ii) in rats with normal or infarcted hearts, the effect of OA on adenine nucleotide metabolism and mechanical function, before and after global ischemia. To investigate the metabolism of OA, normal rats received 100 mg/kg OA, and changes in plasma and tissue concentrations of pyrimidines were examined. The effects of OA were also studied in rats receiving OA for 2 days after coronary ligation or sham operations, and plasma and tissue pyrimidine concentrations examined. Their hearts were isolated and perfused, then subjected to 30 min of global ischemia. Mechanical function and adenine nucleotide content were assessed pre- and post-ischemia. In normal, unoperated rats, administration of 100 mg/kg OA significantly increased hepatic uracil and cytosine nucleotide concentrations, then increased plasma uridine (+124%) and cytidine (+55%), and transiently increased myocardial uracil nucleotides (+21%). Infarction significantly reduced recovery of cardiac work after global ischemia (sham=62%; infarct=26%; P<0.05), and OA treatment in infarcted hearts increased post-ischemic work by 192% (P<0.05), but not in shams. Pre-ischemic ATP was reduced in the surviving myocardium of infarcted hearts from 21.7+/-0.8 to 14.7+/-0. 7 micromol/g dry weight (P<0.001) and total adenine nucleotides (TAN) from 30.3+/-0.8 to 22.4+/-1.1 micromol/g dry weight (P<0.001). OA treatment prevented these reductions in infarcted hearts (ATP 20. 7+/-0.5; TAN, 29.1+/-0.6 micromol/g dry weight). We conclude that OA protects the infarcted heart against global ischemia by enhancing hepatic release of pyrimidine nucleosides into the plasma, which then prevent depletion of adenine nucleotides in the surviving myocardium.

Adenine Nucleotides↗
PubMedDate not supplied

[Effectiveness of orotic acid and calcium pangamate in experimental liver dystrophy].

In tests staged on albino rats with acute dystrophy of the liver provoked with carbon tetrachloride the effect of orotic acid and calcium pangamate on the functional state of the liver was studied. Combined application of orotic acid and calcium pangamate was found to promote a more complete restoration of an intensive secretion of bile, synthesis and secretion of cholates together with bile, formation and secretion of bilirubin, excretion of cholesterol than this could be achieved by separate application of these compounds.

Acute Disease↗
PubMed1985

[The effect of the systemic and intraventricular application of orotic acid on monosynaptic evoked potentials in the dentate gyrus in free-moving rats].

In 20 freely moving Wistar rats the influence of systemically and intraventricularly applied orotic acid derivatives on monosynaptically evoked field potentials registered in the dentate gyrus on the stimulation of the medial entorhinal cortex was investigated. Both, methylglucamine-orotate and tris-orotate led to an increase of the amplitude of the population spike. The slope function of the field EPSP, however, remained unchanged. The effect has been observed to begin 2 h after application and had a duration of 6-10 h. The data obtained in a monosynaptic pathway targeting on a brain structure which is known to play a crucial role in memory formation support earlier findings of a transient effect of orotic acid on cerebral excitation processes. An influence on mechanisms of spike generation or other postsynaptic membrane processes might be assumed.

Animals↗
PubMed1981

[Effect of orotic acid, calcium pangamate, and lipamide on ultrastructural changes in lipocytes in hepatic dystrophy].

Experiments on 50 albino rats with liver dystrophy caused by carbon tetrachloride have shown that orotic acid calcium pangamate and lipamide decrease the damage to subcellular structures of hepatocytes, favour normalization of cytoplasmatic cell components. Combined use of orotic acid and calcium pangamate was found to promote more positive effect on membranous constituents and hyperplastic processes in liver parenchymal cells as compared with the effect that might be attained by applications of the drugs alone. The combined use of the drugs is also conducive to more intensive intracellular reparative regeneration.

Animals↗