Cytidine and Uridine Requirement of the Brain*†

Geiger, A.; Yamasaki, Seiichirō

doi:10.1111/j.1471-4159.1956.tb12059.x

Cited by 143 publications

(31 citation statements)

References 8 publications

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“…The nucleoside cytidine, once it is phosphorylated (Santos et al ., 1968) to form the nucleotides cytidine triphosphate (CTP), cytidine diphosphate (CDP), and cytidine monophosphate (CMP), exerts important effects on a variety of brain functions (Geiger and Yamasaki, 1956;Roberts, 1973 ;Drago et al ., 1990 A . 378 cell culture systems and in vivo experiments, exogenous cytidine has been shown to be taken up into cells and converted sequentially to CMP, CDP, and CTP (Plagemann, 1971a,b ;Trovarelli et al ., 1982;Lopez G.-Coviella and Wurtman, 1992) .…”

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Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices

Savci

Wurtman

1995

Journal of Neurochemistry

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Concurrent exposure to cytidine (200^and ethanolamine (20^also caused significantly greater elevations (p < 0.05) in tissue PE levels than those caused by cytidine alone. In contrast, the addition of serine (500 did not enhance cytidine's effects on any membrane phospholipid . Exposure to serine alone, however, like exposure to sufficient choline, increased levels of all three membrane phospholipids significantly (p < 0.01) . These data show that exogenous cytidine, probably acting via CTP and the Kennedy cycle, can increase the synthesis and levels of membrane PC and PE in brain cells.

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confidence: 99%

Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices

Savci

Wurtman

1995

Journal of Neurochemistry

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“…Furthermore, regional vascular changes following altered metabolic activity of nerve cells could result in an increased removal of tracer substance administered intraventricularly, just as it may increase the local concentration following intravascular administration (Altman, 1963 (Robertson, 1957). It is at least possible that the nucleoside 'pool' has changed as a result of altered respiratory coenzyme synthesis following nerve division (Geiger & Yamasaki, 1957;Friede, 1959). Simple measurement of the activity of precursors incorporated into RNA or protein (Brattgard, Hyden & Sj6strand, 1958;Fischer, Lodin & Kalousek, 1958) is therefore of little value.…”

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confidence: 99%

An autoradiographic study of the incorporation of nucleic‐acid precursors by neurones and glia during nerve regeneration.

Watson¹

1965

The Journal of Physiology

224

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Recent advances in quantitative microanalysis (Edstr6m, 1953(Edstr6m, , 1960 have permitted measurement of change in ribonucleic acid (RNA) content of individual neurones after cutting their axons (Brattgard, Edstr6m & Hyden, 1957). As measurement of a cell's content of RNA alone can give little indication of its dynamic intracellular turnover, the present investigation was undertaken with tritium (3H) labelled precursors of RNA. Their incorporation into various subcellular compartments was detected autoradiographically. The investigation also includes a study of deoxyribonucleic acid (DNA) synthesis within perineuronal oligodendroglia. METHODSAnimals. Most observations were made upon albino mice aged 3 months at the time of nerve division: they received standard food pellets and water supplemented with bread and milk ad libitum. The observations were repeated upon rats and rabbits of the same age.Nerve division. Under general anaesthesia the left hypoglossal nerve was mobilized for about 5 mm where it crossed the interval between internal and external carotid arteries. In some animals the nerve was crushed with fine watchmaker's forceps for 10 sec; in others, the nerve was cut with sharp scissors, and the distal part avulsed from the tongue to impede regeneration. In a few animals the nerve was ligated with silk at this level. In all, care was taken to avoid traction upon the proximal portion of nerve. The animals were allowed to survive up to 80 days after the operation.In other mice, the facial nerve was interrupted similarly where it passed superficially, inferior to the cartilaginous external auditory meatus and posterior to the common facial vein.Isotope administration. Tritiated uridine (1-22 c/m-mole), adenosine (0-68 c/m-mole), and guanosine (89-3 mc/m-mole) were used as precursors of RNA. Tritiated thymidine (3-3 c/mmole) allowed the synthesis of DNA in glial cells to be followed, and tritiated lysine (54 7 mc/ m-mole) was used to indicate protein synthesis. All isotopes were obtained from the Radiochemical Centre, Amersham.In early experiments the labelled compound was diluted with an electrolyte solution, such that the final composition represented that of cerebrospinal fluid (Mitchell, Loeschke, Massion & Severinghaus, 1963); in later experiments, water was used: no difference resulted from this change of solvent. The final activity of the solutions of [3H]lysine, [3H]adenosine,[3H]guanosine and [3H]uridine was 1 c/ml.: [3H]thymidine was diluted to 0-25 c/ml. Twenty

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“…The clearest indication of the role of the liver in providing pyrimidine nucleosides for the brain comes from a beautiful series of experiments by Geiger (53) and Geiger and Yamasaki (54). Using isolated, perfused cat brain they demonstrated that the presence of cytidine and uridine in the blood is essential for maintaining normal brain functions.…”

Section: De Novo Versus Reutilization Pathways: Possible Role Of Livermentioning

confidence: 99%

“…Insertion of the liver into the circulation corrects the changes in carbohydrate metabolism and allows survival for 2-3 hr. Geiger and Yamasaki (54) showed that inclusion of the liver was unnecessary if small amounts of cytidine and uridine were included in the perfusate. Addition of these nucleosides apparently facilitated the transfer of glucose into the brain, which restored the brain lactic acid and glucose concentrations t o normal and allowed survival for 5 hr.…”

Section: De Novo Versus Reutilization Pathways: Possible Role Of Livermentioning

confidence: 99%

A Review: Biological and Clinical Aspects of Pyrimidine Metabolism

1974

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Interest in pyrimidine nucleotide biosynthesis has stemmed largely from the importance of these molecules as components of nucleic acids. Regulation of pyrimidine biosynthesis has been most extensively investigated in micro-organisms in which cell division is effectively controlled by regulation of the activity of the enzymes of the d e n o v o pathway (77, 11 0). The relation between pyrimidine biosynthesis and cellular proliferation in mammals has become clearer with the accumulation of a considerable body of evidence which indicates that there is a close correlation between the activity of enzymes involved in pyrimidine biosynthesis and the rate of cellular proliferation.The d e n o v o pyrimidine biosynthetic pathway and the urea cycle b o t h utilize carbamyl phosphate, and important nitrogen carrier. The biosynthesis of pyrimidine and purine nucleotides are connected by a common intermediate, phosphoribosyl pyrophosphate (PRPP). In addition, pyrimidine nucleotides act as sugar and phospholipid carriers and are important in lipopolysaccharide biosynthesis. The importance of these interrelations is most forcibly emphasized b y certain clinical phenomena which will be discussed later. This paper will attempt t o review the broad biologic aspects of pyrimidine nucleotide biosynthesis. A detailed consideration of d e n o v o pyrimidine biosynthesis in eucaryotic cells is available in the recent review by Jones (81). Pyrimidine biosynthesis in procaryotes has been reviewed in depth by O'Donovan and Neuhard (1 10). PATHWAYS O F PYRIMIDINE NUCLEOTIDE BIOSYNTHESISIn cells from multicellular organisms, pyrimidine nucleotide biosynthesis can proceed b y two mechanisms. D e n o v o biosynthesis of uridylic acid proceeds from simple components such as carbon dioxide, a source of nitrogen (either ammonia or the amide nitrogen of glutamine), ATP, aspartate. and ribose in the form of phosphoribosyl p y r~p h o s~h a t e . A reutilization ("salvage") mechanism is also available t o cells.-.whereby preformed pyrimidine bases o r nucleosides can be converted t o the nucleotide by the addition of ribose phosphate or phosphate. DE NOVO MECHANISMD e n o v o biosynthesis of uridylic acid required six enzymatic steps (Fig. 1). In procaryotes one enzyme supplies the carbamyl phosphate required for both pyrimidine nucleotide and arginine biosynthesis. Consequently, aspartate transcarbamylase is the first enzyme unique to the d e n o v o pyrimidine pathway and an important locus for control of the pathway (77).In contrast, in ureotelic vertebrates, there are t w o carbamyl phosphate synthetases. The first, carbamyl phosphate synthetase I, is located in the inner membrane of the mitochondrion of the liver and also appears t o be present in small quantities in kidney and small intestine (82). The second, carbamyl phosphate syntlietase 11, has a more ubiquitous distribution and was first demonstrated t o be present in Ehrlich ascites cells (58,59) and in hematopoietic mouse spleen (75,143). This enzyme was originally difficult t o dete...

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Cytidine and Uridine Requirement of the Brain*†

Cited by 143 publications

References 8 publications

Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices

Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices

An autoradiographic study of the incorporation of nucleic‐acid precursors by neurones and glia during nerve regeneration.

A Review: Biological and Clinical Aspects of Pyrimidine Metabolism

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