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PubMedDate not supplied

[Coordination of the main and reutilization pathways of nucleotide biosynthesis in the lymphocytes in leukemia].

Coordination of these two pathways of nucleotide synthesis in leukocytes under chronic lympholeukosis was studied using incorporation of 14C-orotic acid and 14C-uridine into uridine mono-, di- and triphosphates and also into RNA. Simultaneously, activity of the key enzymes, participating in metabolism of orotic acid and of uridine, was measured: OMP-pyrophosphorylase /EC 2.4.2.10, orotidine-5'-phosphate: purophosphate phosphorybosyl transferase/ and uridine kinase /EC 2.7.1.48, ATP: uridine-5'-phosphotransferase/. The reutilizational pathway of pyrimidine nucleotide synthesis was distinctly activated. At the same time there was only a slight increase in the main pathway of their synthesis in lymphocytes in leukemic form of cronic lympholeukosis. Activities of OMP-pyrophosphorylase and uridine kinase were increased by 30%. An impairment in the coordination of the rates of both pathways of pyrimidine nucleotide synthesis was related to inhibition of OMP-pyrophosphorylase caused by and increase in uridine nucleotide pool.

Enzyme Activation↗
PubMed1975

Inhibition, by drugs, of galactosamine induced hepatitis in the rat.

Four compounds, prednisolone, sodium phenobarbitone, azathioprine and orotic acid, were tested for their ability to inhibit galactosamine induced hepatitis in the rat. Prednisolone offered total protection at doses of 100 mg/kg and above; sodium phenobarbitone and orotic acid modified the response to galactosamine and azathioprine was without effect.

Alanine Transaminase↗
PubMed1976

Purine metabolism in adenosine deaminase deficiency.

Purine and pyrimidine metabolites were measured in erythrocytes, plasma, and urine of a 5-month-old infant with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. Adenosine and adenine were measured using newly devised ion exchange separation techniques and a sensitive fluorescence assay. Plasma adenosine levels were increased, whereas adenosine was normal in erythrocytes and not detectable in urine. Increased amounts of adenine were found in erythrocytes and urine as well as in the plasma. Erythrocyte adenosine 5'-monophosphate and adenosine diphosphate concentrations were normal, but adenosine triphosphate content was greatly elevated. Because of the possibility of pyrimidine starvation, pyrimidine nucleotides (pyrimidine coenzymes) in erythrocytes and orotic acid in urine were measured. Pyrimidine nucleotide concentrations were normal, while orotic acid was not detected. These studies suggest that the immune deficiency associated with adenosine deaminase deficiency may be related to increased amounts of adenine, adenosine, or adenine nucleotides.

Adenine↗
PubMed1978

Dietary protein intake and arginine requirements in the rat.

Experiments were conducted with immature rats fed L-amino acid purified diets varying in total N and arginine. The experiments demonstrated that total N intake was the factor responsible for increased orotic acid excretion during arginine deficiency. Increased orotic acid excretion was accompanied by increased liver transaminase activities and increased liver concentrations of NH4-N and glutamine. Arginine requirements for growth and normal metabolite excretion increased as dietary N was increased. Accompanying elevated urinary citrate during N deprivation and arginine deficiency was a depression of liver isocitrate dehydrogenase activity. Citrate excretion was lower if arginine was fed as the HCl compared to the free base. During a partial or total arginine deficiency citrate excretion was elevated at varying dietary N concentrations. Urinary pH was not significantly changed by level of dietary N or arginine.

Amino Acids↗
PubMed1986

Increased formation and keeping of ribosomes during dietary recovery of mouse kidney.

In the kidney of 5-day protein-depleted mice there is a decrease of 23% in the rRNA mass. When these animals are fed with a complete diet, rRNA content is restored to its normal value after 24 h of refeeding. The mechanisms that underlie this phenomenon were studied. It was found that the activity of rRNA polymerase I in the nuclei of kidneys from refed mice showed an increase of about twofold compared with the activity in normal and protein-depleted nuclei. The in vivo incorporation of a large dose (nontrace) of [14C]orotic acid into rRNA was also twofold enhanced in kidneys from refed mice. Ribosome degradation (measured by the disappearance of radioactivity from either ribosomal proteins or rRNA previously labeled by the injection of NaH14CO3 and [14C]orotic acid to the mice, respectively) stopped during the 1st day after refeeding. The estimation of the difference between the rRNA synthesis rate and the net rRNA increase also demonstrated a decrease in the rRNA degradation rate in refed mice.

Animals↗
PubMed1981

Effects of repeated administration of rat 2-diethylaminoethyl-2-2-diphenylvalerate-HCI (SKF 525 A) on liver.

Repetitive administration to male rats of 2-diethylaminoethyl-2-2-diphenyl-valerate-HCI (SKF 525 A) (50 mg/kg, i.p.), decreases the intensity of [14C]-orotic acid incorporation/mg of RNA but not the 14C-incorporation/g liver. The RNA content/g liver is significantly higher in SKF-treated animals than in controls. Decay of label in liver RNA from [14C] orotic acid pretreated animals, is not significantly different in SKF 525 A treated animals than in controls. SKF 525 A repetitive administration, does not modify the rate of incorporation of 32P in liver microsomal lipid when results are expressed per microgram of inorganic phosphorus but it does when expressed in terms of per gram liver. There is a significant decrease in the decay rate of label from 32P-prelabeled liver microsomal phospholipids when animals are treated with SKF 525 A. There is a significant increase in the protein and phospholipid content in the smooth endoplasmic reticulum fraction. The electron microscopy of liver from SKF 525 A-treated animals, shows the presence of large areas of round vesicles of swollen endoplasmic reticulum, partly due to smooth component and part due to rough component, having detached the ribosomes from their membranes. Results suggest an inhibitory effect of SKF 525 A on RNA and phospholipid degradative processes.

Animals↗
PubMed1993

Efficiency of hemodialysis of pyrimidine compounds in patients with chronic renal failure.

The accumulation in blood plasma and efficiency of hemodialysis of pyrimidine compounds (orotic acid, orotidine, pseudouridine, uridine, thymine) as well as uric acid and creatinine in 23 patients with chronic renal failure (CRF) was investigated. As a reference, the analysis of the above metabolites in the plasma of 30 healthy volunteers was performed. Among examined compounds, pseudouridine possessed the highest capability of accumulation in blood plasma (25 times higher concentration than physiological). It coincided with the lowest efficiency of pseudouridine hemodialysis (44%) and the longest T1/2 (relative to creatinine) in plasma. A significant linear correlation (r = 0.81, p < 0.001) between efficiency of creatinine and pseudouridine hemodialysis was calculated. The concentration of orotic acid in the blood plasma of patients before hemodialysis exceeded 14 times its level in healthy subjects; the inhibition of uric acid synthesis by allopurinol in dialyzed patients was accompanied by enlargement of orotidine and orotate accumulation in blood plasma. Extremely high plasma concentration of examined pyrimidines remaining elevated after hemodialysis creates an additional hazard for tissue metabolism and health of patients with CRF.

Adult↗
PubMed1984

Metabolites of nucleic acids in bovine milk.

To investigate metabolites of nucleic acids in milk as by-products of protein biosynthesis, a method for determination of pyrimidine and purine compounds by reversed-phase high-pressure liquid chromatography was developed. Reproducibility of the measured compounds was 2%. Recovery of the main constituents averaged about 99%. In addition to orotic acid, allantoin, and uric acid, the free bases hypoxanthine, xanthine, and guanine, the ribonucleosides uridine, cytidine, and pseudouridine, and the ribonucleotides, guanosine 5'-monophosphate and cytidine 5'-monophosphate, were quantified in milk samples of Holstein-Friesian cows. Milk production from days 45 to 65 of lactation influenced concentrations of individual metabolites differently. Concentrations of orotic acid, allantoin, and uric acid decreased with increasing milk production, whereas concentrations of uridine, cytidine, pseudouridine, hypoxanthine, xanthine, and guanine remained unchanged. The results allowed conclusions on rate limiting steps of catabolic pathways of pyrimidines and purines and indicated relationships with protein biosynthesis. A possible role of metabolites of nucleic acids as taste factors and as substrates for milk microbes is suggested.

Allantoin↗
PubMed1977

Enzymes of ammonia detoxication after portacaval shunt in the rat. I. Carbamylphosphate synthetase and aspartate transcarbamylase.

At high systemic blood concentrations ammonia may be partially deviated into the pathway of pyrimidine synthesis, as has been observed in different genetic defects of the urea cycle. The portacaval shunt (PCS) rat presents an animal model to study ammonia detoxication without an underlying enzyme defect in the urea cycle. Since ammonia may induce a deviation into the pyrimidine pathway by influencing enzymatic reactions involved in this pathway, the activity of carbamylphosphate synthetase and aspartate transcarbamylase in liver as well as the excretion of orotic acid in the urine were measured in rats 10, 20 and 30 days after PCS. The results suggest that in this experimental model ammonia may be channeled into the pyrimidine pathway leading to a stimulation of the first enzymatic step and to an increased excretion of orotic acid.

Ammonia↗
PubMed1985

Integrated study of the structural and metabolic degeneration of skin during 4 degrees C storage in nutrient medium.

Integrated studies of the structural and metabolic degradation of skin during 4 degrees C refrigerated storage in Eagle's minimal essential medium were undertaken. Skin degeneration occurred in three phases during the first 7 weeks of refrigeration. Phase I (Days 1-10) was characterized by the release of cellular debris and leakage of intracellular enzymes into the storage medium, shrinkage of the epithelium, and vacuolization and cell loss in the vascular bundles of the papillary dermis. The release of debris was accelerated by a 2-hr incubation of the skin at 25 and 37 degrees C prior to 4 degrees C storage. The ability of dermal cells to metabolize glucose, aspartic acid, glutamic acid, ornithine, and orotic acid to carbon dioxide dropped to low levels during Phase I. Phase II (Days 11-30) was characterized by a period of less intense physical decay, but with continued cellular and vascular degeneration. By the third week, there was nearly total loss of recognizable vascular bundles in the papillary dermis. Phase III (Days 31-58) was characterized by the exfoliation of large amounts of cellular debris and significant loss of structural integrity. By the fifth week, nearly all of the nuclei in the epidermis became pyknotic, and the vascular bundles of the reticular dermis were lost. Previous reports of the maximum allowable duration of skin storage at 0-8 degrees C have ranged from 0.3 to 185 days; however, our findings suggest that the useful limit of refrigerated skin storage in nutrient medium is 1 week if physiological function and structural integrity are desired for optimum postgraft performance.

Animals↗
PubMed1992

Peculiarities of functioning of protein-synthesizing apparatus of the hibernator (Citellus undulatus).

Synthesis of proteins and RNA has been studied by means of labeled precursors of 14C-labeled amino acids and [14C]orotic acid in liver cells of hibernating, arousing, and active ground squirrels (Citellus undulatus). The investigations indicate that cycloheximide (CHI)-inhibited protein synthesis in liver cells of hibernating ground squirrels may occur on preexisting polyribosomes. A low level of protein synthesis in this state results not only from the Arrhenius dependence, but also from the dissociation of polyribosomes into monosomes. During arousal there is an intensive assembly of polyribosomes. This occurs even with the inhibition of RNA synthesis by actinomycin D, testifying to the presence of a pool of iRNA in liver cells, which is necessary to activate translation. The intensity of protein synthesis in arousal is also influenced by the activation of transcription.

Animals↗
PubMed1982

Pyrimidine metabolism in Giardia lamblia trophozoites.

The pyrimidine metabolism of Giardia lamblia trophozoites (Portland I strain) was studied using whole trophozoites and trophozoite homogenates. Pyrimidines and pyrimidine nucleosides were readily incorporated into nucleic acids. Orotic and aspartic acid incorporations were below the level of detection. Enzymes of the pyrimidine salvage pathway (i.e., thymidine and uridine phosphorylases and thymidine and uridine kinases) were detected in trophozoite homogenates, but the activities of de novo pyrimidine synthesis enzymes (i.e., carbamoyl-phosphate synthase, aspartate transcarbamoylase, dihydroorotase and dihydroorotate dehydrogenase) were below the level of detection in these same homogenates. The evidence presented supports the conclusion that G. lamblia trophozoites appear incapable of synthesizing pyrimidines de novo but are capable of salvaging preformed pyrimidines and pyrimidine nucleosides from the growth medium and the enzymes of this pyrimidine salvage pathway are not organelle associated.

Animals↗
PubMed1997

A syndrome of congenital hyperinsulinism and hyperammonemia.

This report describes two patients from unrelated families with an unusual syndrome of hyperinsulinism plus hyperammonemia. The diagnosis of hyperinsulinism was based on the demonstration of fasting hypoglycemia with inappropriately elevated insulin levels, inappropriately low beta-hydroxybutyrate and free fatty acid levels, and inappropriately large glycemic response to the administration of glucagon. In both patients, plasma ammonium levels were persistently elevated and unaffected by protein feeding, protein restriction, or benzoate therapy. Plasma and urinary amino acids, urinary organic acids, and urinary orotic acid levels were not consistent with any of the urea cycle enzyme defects or other hyperammonemic disorders. These two patients appear to represent a unique form of congenital hyperinsulinism distinct from the previously described autosomal dominant and autosomal recessive variants. We speculate that the underlying defect involves a site that is common to the amino acid regulation of both insulin secretion in pancreatic beta-cells and urea synthesis in the liver.

Ammonia↗
PubMedDate not supplied

Persistent hyperammonemia in two related Morgan weanlings.

Persistent hyperammonemia was diagnosed in 2 Morgan fillies with clinical signs that developed early in the postweaning period. Diagnostic evaluation, including routine serum chemistries, CBC, liver biopsy, hepatic ultrasonography, liver function test, and necropsy findings did not support a toxic, developmental, or infectious cause. Abnormal serum amino acid and urine orotic acid concentrations suggest that the foals may have had an inherited disorders described in humans as hyperornithinemia, hyperammonemia, and homocitrullinuria (HHH) syndrome. The disorder is thought to be caused by a defective mitochondrial transporter protein, such that ornithine, required for complete urea synthesis, is deficient, thus causing increases in blood ammonia and ornithine concentrations.

Amino Acids↗
PubMed1980

Ribonucleic acid metabolism during planarian regeneration.

A method for the extraction of total RNA of the planarian Polycelis tenuis is described. This technique has been applied to the study of RNA synthesis in the course of regeneration. Synthesis of RNA begins 7 hrs after sectioning and proceeds in two phases. The first phase, from 7 to 21 hr is characterized by an increased rate of (3H) orotic acid incorporation into RNA up to the 18th after sectioning followed by a decrease between 18 and 21 hrs. The rate of precursor incorporation then had risen again in the second phase to the 30th hr and finally decreased slowly until completion of regeneration. Studies of the pool of nucleotide precursors, show that the observed variations of orotic acid incorporation into RNA reflect variations in RNA synthesis. Electrophoretic analysis of RNA labelled for 2 hrs at various times during regeneration shows that the product formed during the first phase of regeneration is mainly rRNA and low molecular weight RNA. The second phase of the regeneration process, from the 24th hr, is characterized by the appearance of both ribosomal and polydisperse RNAs. These heterogeneous RNA species are detected up to the 46th hr of regeneration, after which time rRNA again becomes predominent. The significance of the two phases of RNA metabolism of which this is the first observation during planarian regeneration is discussed in connection with other biochemical events which have been described during regeneration processes in planarians and other animals.

Animals↗
PubMed1975

Effect of plasma lipid levels and obesity on tissue stores of alpha-tocopherol.

Experiments were designed to determine how varying levels of plasma lipids affect tissue deposition of alpha-tocopherol (vitamin E). Hypolipemia was induced by feeding orotic acid, and hyperlipemia was obtained using genetically obese rats. With equal dietary intakes of alpha-tocopherol, hypolipemic rats had lower plasma and tissue concentrations than rats with normal plasma lipids. An exception was liver, which due to fatty enlargement from orotic acid had more alpha-tocopherol. Hyperlipemic obese rats had plasma total lipids and alpha-tocopherol three times those of normal rats with the same intake of alpha-tocopherol. Tissue concentrations of the vitamin, however, were considerably lower in obese rats. Due to their large adipose mass, obese rats had considerably more total body alpha-tocopherol than normal rats. It was concluded that both plasma lipid levels and degree of adiposity are important factors in determining tissue deposition of alpha-tocopherol.

Adipose Tissue↗
PubMed1980

The effect of short term incubation in vitro on the RNA content of regenerating mouse epidermis.

The effect of short term incubation in vitro on RNA content in regenerating and normal epidermis has been investigated. Regenerating mouse epidermis was incubated for three hours, either attached to its underlying dermis or by itself, in either buffered sucrose or Roswell Park Memorial Institute culture medium at 26 degrees C or at 37 degrees C. There is a significant loss of RNA when regenerating epidermis is incubated without being attached to its underlying dermis, at either 26 degrees C or 37 degrees C, although there was little loss of DNA, good incorporation of (3H) orotic acid into RNA, as well as good preservation of epidermal histological details. In contrast, when regenerating epidermis was incubated attached to its dermis, little loss of RNA occurred. Similarly, incubating normal epidermis attached to its dermis results in no loss of RNA. These conditions also result in no significant loss of DNA, good incorporation of (3H) orotic acid into RNA, and preservation of epidermal histological details.

Animals↗
PubMed2003

High-resolution diffusion and relaxation-edited magic angle spinning 1H NMR spectroscopy of intact liver tissue.

High-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy is ideal for monitoring the metabolic environment within tissues, particularly when spectra are weighted by physical properties such as T(1) and T(2) relaxation times and apparent diffusion coefficients (ADCs). In this study, spectral-editing using T(1) and T(2) relaxation times and ADCs at variable diffusion times was used in conjunction with HRMAS (1)H NMR spectroscopy at 14.1 T in liver tissue. To enhance the sensitivity of ADC measurements to low molecular weight metabolites a T(2) spin echo was included in a standard stimulated gradient spin-echo sequence. Fatty liver induced in rats by chronic orotic acid feeding was investigated using this modified sequence. An increase in the combined ADC for the co-resonant peaks glucose, betaine, and TMAO during fatty liver disease was detected (ADCs = 0.60 +/- 0.11 and 0.35 +/- 0.1 * 10(-9) m(2)s(-1) (n = 3) for rats fed with and without orotic acid), indicative of a reduction in glucose and betaine and an increase in TMAO.

Animals↗