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Results for “Pyrimidine Nucleotides”

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At least 19 recordsLinked to original sources
PubMed1986

Growth of Lactobacillus bulgaricus in milk. 2. Characteristics of purine nucleotides, pyrimidine nucleotides, and nucleic acid synthesis.

Lactobacillus bulgaricus incorporated exogenous guanine only into guanine nucleotides and not into adenine nucleotides. Lactobacillus bulgaricus lacks the ability to interconvert adenine nucleotides and guanine nucleotides. Biosynthesis of pyrimidine nucleotides from orotic acid was depressed by addition of guanosine monophosphate or adenosine monophosphate. Some step in pyrimidine biosynthesis from orotic acid may be negatively regulated by the intracellular amount of purine nucleotides. Lactobacillus bulgaricus could not grow in milk from which orotate was removed. This indicates that the activity of de novo pyrimidine synthesis is very low in this organism. When the intracellular amount of purine or pyrimidine base was limited, ribonucleic acid synthesis was markedly depressed, resulting in cell elongation, whereas deoxyribonucleic acid synthesis was not so much affected.

Adenine↗
PubMed1977

Lead poisoning. Further observations on erythrocyte pyrimidine-nucleotidase deficiency and intracellular accumulation of pyrimidine nucleotides.

Pyrimidine nucleotides, detectable in normal erythrocytes only in trace quantities if at all, were found to comprise 7-80% of the intracellular nucleotide pools in nine subjects with severe lead over-burden. Blood lead concentrations ranged from approximately equal to 200- to 400-microgram/dl packed cells, and the greatest accumulations of pyrimidine-containing nucleotides occurred in the two subjects with the highest blood lead levels. Most of the patients had mild or moderate anemia and moderate basophilic stippling evident in Wright's-stained peripheral smears. Pyrimidine nucleotidase activities were inhibited to 13-28% of the mean activity in normal control erythrocytes and even more so (5-15%) when compared to specimens with increased reticulocytes and young cells. Reticulocytosis was absent in two subjects and modest to moderate in the remainder, but erythrocyte assays revealed the substantial elevations in populations of young mean cell age. Inappropriately low reticulocyttial elevations in glucose-6-phosphate dehydrogenase expected in populations of young mean cell age. Inappropriately low reticulocyte responses may reflect hematopoietic suppressive effects of lead at a variety of metabolic loci.

Cell Count↗
PubMed1997

Dihydroorotat-ubiquinone oxidoreductase links mitochondria in the biosynthesis of pyrimidine nucleotides.

Pyrimidines and purine (deoxy)nucleotides are the building blocks of DNA and RNA. Nucleoside diphosphate sugars, e.g. UDP-glucose, are the reactive intermediates in the synthesis of nearly all glycosidic bonds between sugars. In mammals the requirement for pyrimidines is met by UMP de novo synthesis and, to a greater or lesser extent, by salvage of free nucleosides. The exceptional compartmentation of the de novo synthesis with respect to mitochondrially-bound dihydroorotate dehydrogenase ('DHOdehase' or 'DHODH', EC 1.3.99.11) is one focus of the present work. DHODH activity was determined by the dihydroorotate-dependent oxygen consumption or by the UV absorption of the product orotate with mitochondria isolated from rodent and porcine tissues. For comparison, the cytochrome c and choline-dependent oxygen consumption of mitochondria from different tissues was measured. The highest specific activity of the rat DHODH was found in liver (2.3 x 10(-3) mumol/min x mg protein) > kidney > heart. The application of known enzyme inhibitors Brequinar Sodium and Leflunomide for DHODH and sodium cyanide for cytochrome c oxidase verified the specificity of the activity tests used. The relation of DHODH activity versus that of cytochrome c oxidase revealed the lowest ratios in heart mitochondria and the highest in liver mitochondria. Since disorders in the mitochondrial energy metabolism could entail severe impairment of pyrimidine biosynthesis via respiratory-chain coupled DHODH, it is suggested to include improvement of pyrimidine nucleotide status in therapy protocols.

Animals↗
PubMed1993

Pyrimidine nucleotide metabolism in rat hepatocytes: evidence for compartmentation of nucleotide pools.

Pyrimidine nucleotide metabolism in rat hepatocytes was studied by measurement of the labelling kinetics of the various intermediates after double labelling with [14C]orotic acid and [3H]cytidine, the precursors for the de novo and the salvage pathways respectively. For the uridine nucleotides, differences were found for the 14C/3H ratios in the UDP-sugars, in UMP (of RNA) and in their precursor UTP, suggesting the existence of separated flows of the radioactive precursors through the de novo and the salvage pathways. Higher ratios in the UDP-sugars, which are synthesized in the cytoplasm, and a lower ratio in UMP (of RNA) relative to the 14C/3H ratio in UTP indicated that UTP derived from orotic acid is preferentially used for the cytoplasmic biosynthesis of the UDP-sugars. Uridine, derived from cytidine, is preferentially used for the nuclear-localized synthesis of RNA. In contrast to these findings, the 14C/3H ratios in the cytidine derivatives CMP-NeuAc and CMP (of RNA), and in the liponucleotides CDP-choline and CDP-ethanolamine, were all lower than that in the precursor CTP. This indicates a preferential utilization of the salvage-derived CTP for the synthesis of the liponucleotides as well as for RNA and CMP-NeuAc. Similar conclusions could be drawn from experiments in which the intracellular amounts of several uridine- and cytidine-nucleotide-containing derivatives were increased by preincubating the hepatocytes with unlabelled pyrimidine nucleotides or ethanolamine. Based on these data, we propose a refined model for the intracellular compartmentation of pyrimidine nucleotide biosynthesis in which three pools of UTP are distinguished: a pool of de novo-derived molecules and a pool of salvage-derived molecules, both of which are channelled to the site of utilization; in addition an 'overflow' pool exists, consisting of molecules having escaped from channelling. An overflow pool could also be distinguished for CTP, but no discrimination between de novo and salvage-derived molecules could be made.

Animals↗
PubMed1991

Inhibition of hexose monophosphate shunt in young erythrocytes by pyrimidine nucleotides in hereditary pyrimidine 5' nucleotidase deficiency.

Recent reports have suggested that haemolytic anaemia in pyrimidine 5' nucleotidase (P5'N) deficiency might be due to impaired erythrocyte hexose monophosphate shunt (HMS). To investigate the relationship between pyrimidine accumulation, HMS impairment and shortened red-cell survival, we tested glucose 6-phosphate dehydrogenase (G-6PD), HMS, P5'N activities and the UV spectrum in whole red cells and in red cells of different age from 2 P5'N-deficient patients with different degrees of haemolytic anaemia. In whole red cells we found a reduction of both G-6PD and stimulated HMS activity in the presence of a variable amount of pyrimidine nucleotides (37.79 and 17.88 mumol/gHb respectively). A drastic inhibition of stimulated HMS activity was already present in the lightest red-cell fractions from patient 1, who presented a more severe haemolytic anaemia. The variable degree of pyrimidines found among red cell fractions, with a minor accumulation in the older red cells, supports the hypothesis that pyrimidine accumulation and HMS impairment occur in the younger erythrocytes of P5'N-deficient patients.

5'-Nucleotidase↗
PubMed2003

Differential control of cell cycle, proliferation, and survival of primary T lymphocytes by purine and pyrimidine nucleotides.

Purine and pyrimidine nucleotides play critical roles in DNA and RNA synthesis as well as in membrane lipid biosynthesis and protein glycosylation. They are necessary for the development and survival of mature T lymphocytes. Activation of T lymphocytes is associated with an increase of purine and pyrimidine pools. However, the question of how purine vs pyrimidine nucleotides regulate proliferation, cell cycle, and survival of primary T lymphocytes following activation has not yet been specifically addressed. This was investigated in the present study by using well-known purine (mycophenolic acid, 6-mercaptopurine) and pyrimidine (methotrexate, 5-fluorouracil) inhibitors, which are used in neoplastic diseases or as immunosuppressive agents. The effect of these inhibitors was analyzed according to their time of addition with respect to the initiation of mitogenic activation. We showed that synthesis of both purine and pyrimidine nucleotides is required for T cell proliferation. However, purine and pyrimidine nucleotides differentially regulate the cell cycle since purines control both G(1) to S phase transition and progression through the S phase, whereas pyrimidines only control progression from early to intermediate S phase. Furthermore, inhibition of pyrimidine synthesis induces apoptosis whatever the time of inhibitor addition whereas inhibition of purine nucleotides induces apoptosis only when applied to already cycling T cells, suggesting that both purine and pyrimidine nucleotides are required for survival of cells committed into S phase. These findings reveal a hitherto unknown role of purine and pyrimidine de novo synthesis in regulating cell cycle progression and maintaining survival of activated T lymphocytes.

Apoptosis↗
PubMed1998

Interactions of hypochlorous acid with pyrimidine nucleotides, and secondary reactions of chlorinated pyrimidines with GSH, NADH, and other substrates.

HOCl-induced chlorination of pyrimidine nucleotides, PyNH, strikingly depends on the nature of the available chlorine acceptor group. For CMP, with an -NH2 group as acceptor, the reaction is slow and involves predominantly the acid [k(CMP + HOCl) approximately 100 M-1 s-1 at pH 6]; apparent rate constants of the reaction decrease around the pK alpha (HOCl), to 0 in alkaline solution. For TMP and UMP, with a heterocyclic > NH group (at 3N) as acceptor, the reaction is faster and involves mainly the conjugated CIO- anion [e.g., k(UMP + ClO-) approximately 3 x 10(4) M-1 s-1 and k(UMP + HOCl) approximately 200 M-1 s-1]. The 3-N-methylthymidine derivative is inert toward HOCl. Reactions of ClO- with TMP, UMP, and poly(U) are shown to be reversible, PyNH + ClO- = PyNCl + OH-; an increase in pH due to this reaction was confirmed, and equilibrium constants have been estimated. The chlorinated derivatives of TMP and UMP are very reactive toward GSH, disulfide, aliphatic amines, and NADH. In contrast, the PyNCl derivative of CMP is unreactive, except with GSH. Rate constants of reactions of PyNCl species with various substrates are presented. Oxidation of NADH, by both HOCl and PyNCl derivatives, leads to a stable product (not NAD+) which is irreversibly degraded by reaction with excess HOCl, but inert toward acsorbate, GSH, and H2O2. Thiols (GSH) and disulfides (DTPA) were previously found capable of scavenging up to four HOCl molecules (Prütz, W. A., Arch. Biochem. Biophys. 332, 110-120, 1996). In the present study it was established that reactions of GSH or DTPA with excess HOCl give rise to a rapid drop in the pH by release of up to four HCl molecules per GSH or DTPA, as expected for a sequence of consecutive sulfoxidations. Reactions of GSH and DTPA with PyNCl efficiently regenerate PyNH, namely up to four molecules per GSH or DTPA in the case of TMP and UMP, but only one molecule per GSH in the case of CMP. The PyNCl derivatives of TMP and UMP transfer chlorine slowly but completely to CMP or AMP. Such chlorine transfer between nucleic acid bases is likely to occur also in DNA; it is shown that HOCl in fact induces a complex series of reactions on interaction with native DNA.

Animals↗
PubMed1998

Basis of pyrimidine nucleotide metabolism in the myocardium.

The metabolism of pyrimidine nucleotides in the myocardium is poorly understood. The turnover of these nucleotides is high, whereas their concentration is rather low. The de novo pathway of synthesis does not seem very efficient, although the utilization of nucleosides could represent the major pathway for pyrimidine nucleotide synthesis. In rat blood, cytidine could be the major precursor for pyrimidine nucleotide synthesis. The precursor, whatever its exact nature (uridine or cytidine), could be species dependent, and the liver could a major role in providing blood nucleosides. Owing to the essential role of pyrimidine nucleotides in the synthesis of macromolecules, acute or chronic alteration of the metabolism of these nucleotides could have crucial consequences on heart viability and function. Providing pyrimidine precursors to the heart, isolated or in situ, induces functional and metabolic effects on the heart. The experimental results suggest that such interventions could be beneficial in clinical situations such as cardioplegia, heart preservation, or recovery from ischemia.

Animals↗
PubMed1980

Pyrimidine nucleotide pool changes during the cell cycle and quiescence. Pyrimidine excretion and metabolic isolation of the pyrimidine mononucleoside polyphosphate pool.

We have measured the pyrimidine nucleotide contents of the culture fluid, acid-soluble fraction, and acid-insoluble fraction of cultures of hamster embryo fibroblasts (third subculture) through the final two divisions of growth in culture. The cells show a growth delay between the penultimate and ultimate division periods and a concomitant biochemical synchrony of pyrimidine metabolism. The cells exhibit normal excretion of pyrimidine nucleotides beginning with the ultimate division cycle. This excretion results from the net breakdown of ribonucleic acid and a cell-regulated maximum for pyrimidine mononucleoside polyphosphate content. This upper limit for the pyrimidine nucleoside polyphosphate content is not a steady state phenomenon but rather an absence of both synthesis and utilization. The hamster embryo fibroblast exhibits a directed flow of salvage uridine for ribonucleic acid synthesis. We show that de novo synthetic uridine 5'-monophosphate also can be used for ribonucleic acid synthesis without prior entry into the cytoplasmic uridine nucleoside polyphosphate pool. During attachment and first division salvage uridine does enter the cytoplasmic nucleotide pool. The properties of the cytidine pools differ from the uridine pools in specific activity and levels of cytidine, due to turnover of the terminal C-C-A of cytoplasmic transfer ribonucleic acid and the delay in conversion of of nonradioactive de novo synthetic uridine 5'-monophosphate to cytidine 5'-triphosphate. The partial synchrony in these cultures has been used as a temporal marker of the observed events.

Animals↗
PubMed2003

Purine and pyrimidine nucleotide metabolism in higher plants.

Purine and pyrimidine nucleotides participate in many biochemical processes in plants. They are building blocks for nucleic acid synthesis, an energy source, precursors for the synthesis of primary products, such as sucrose, polysaccharides, phospholipids, as well as secondary products. Therefore, biosynthesis and metabolism of nucleotides are of fundamental importance in the growth and development of plants. Nucleotides are synthesized both from amino acids and other small molecules via de novo pathways, and from preformed nucleobases and nucleosides by salvage pathways. In this article the biosynthesis, interconversion and degradation of purine and pyrimidine nucleotides in higher plants are reviewed. This description is followed by an examination of physiological aspects of nucleotide metabolism in various areas of growth and organized development in plants, including embryo maturation and germination, in vitro organogenesis, storage organ development and sprouting, leaf senescence, and cultured plant cells. The effects of environmental factors on nucleotide metabolism are also described. This review ends with a brief discussion of molecular studies on nucleotide synthesis and metabolism.

Plant Development↗
PubMed1985

Abnormal erythrocyte pyrimidine nucleotides in uremic subjects.

Uremia causes major increases in the erythrocyte (RBC) purine nucleotides, presumably secondary to phosphate retention, but no previous study has been made of the pyrimidine nucleotides, normally absent from RBC. This investigation was prompted by demonstration of the abnormal presence of RBC pyrimidine nucleotides, primarily cytidine triphosphate (CTP) plus cytidine diphosphate-choline (CDP-C) and cytidine diphosphate-ethanolamine (CDP-E), in two types of congenital hemolytic anemia as well as in lead poisoning. These observations suggested an analogy to the RBC membrane dysfunction of uremia. This is a report of the identification of CDP-C and CDP-E as the predominant abnormal pyrimidine nucleotides in the RBC hemolysates of uremic subjects. High-performance liquid chromatography of hemolysates from uremic adults showed a 50% increase in purine nucleotides and the abnormal presence of pyrimidine nucleotides and diesters at approximately 10% of the concentration of the purine nucleotides. By means of UV spectra and 31P nuclear magnetic resonance, these were identified as CDP-C and CDP-E. The increased purine and abnormal pyrimidine nucleotides of uremic RBC were unrelated to the pre- or posthemodialysis state, allopurinol, levels of blood lead, copper and zinc, or RBC pyrimidine 5'-nucleotidase, the cytosolic enzyme that specifically dephosphorylates the pyrimidine nucleotides. Although the accumulation of CTP, CDP-C and CDP-E may be an epiphenomenon of phosphate retention, it also suggests a common pathway to the accelerated hemolysis of chronic renal insufficiency.

5'-Nucleotidase↗