In-vivo-Untersuchungen zur Metabolisierung der Pyrimidinnucleoside

Dahnke, H.-G.; Mosebach, K.-O.

doi:10.1515/bchm2.1975.356.2.1565

Cited by 17 publications

(4 citation statements)

References 3 publications

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“…Hepatocytes possess the complete pathway for the conversion of uridine into the end-products of pyrimidine catabolism, which has not been detected in nonparenchymal liver cells (31) or other tissues except for the kidneys (26, 40). The rate of hepatic nucleotide formation from extracellular uridine is almost negligible as compared with the rate of its catabolism in hepatocytes (31,36,37,41), the isolated-perfused rat liver (27, 28) and in the liver in uiuo (8,(23)(24)(25)(26). Under the conditions of our perfusion experiments, the rate of uridine uptake (i.e., transport and metabolism) was nearly identical to the rate of uridine catabolite formation.…”

Section: Discussionmentioning

confidence: 99%

“…The liver plays an important role in systemic pyrimidine catabolism under in uiuo conditions (23)(24)(25)(26) and eliminates in a single passage most of the uridine (27,281 and adenosine (29,30) in portal vein blood. A rapid permeation of adenosine and uridine across the cell membrane is a prerequisite for their efficient clearance from the sinusoidal blood by nonparenchymal and parenchymal liver cells (30,31).…”

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confidence: 99%

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Facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver

Holstege

1991

Hepatology

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In mammalian cells, nucleoside transport usually is mediated by facilitated diffusion. In addition, a Na(+)-dependent, concentrative nucleoside transport system has been detected in several tissues but not the liver. To further clarify hepatic nucleoside transport mechanisms, we measured the uptake of [2-14C]uridine (2 to 100 mumol/L) and of [8-14C]adenosine (10 to 75 mumol/L) by the isolated perfused rat liver in the presence or absence of extracellular sodium or specific inhibitors of facilitated nucleoside diffusion. Uridine transport and metabolism were monitored by the release of labeled catabolites including 14CO2, which indicated complete degradation of the pyrimidine. Adenosine, uridine and uridine catabolites were measured in the effluent perfusate by reversed-phase high-performance liquid chromatography and a radioactivity flow monitor. The existence of a Na(+)-dependent nucleoside transport system could be inferred from the following observations: (a) Sodium depletion caused a strong inhibition of nucleoside transport reflected by an up to threefold and 15-fold increase in extracellular uridine and adenosine, respectively. The sodium-dependent transport of uridine was saturated when the influent uridine concentration was raised beyond 20 mumol/L. No such saturation was observed for much higher concentrations of adenosine used (10 to 75 mumol/L). (b) Na(+)-free perfusion resulted in a strong suppression of the release of uridine catabolites by the liver. Complete uridine breakdown was depressed to 7% of the amount of 14CO2 released in the presence of sodium and at influent uridine concentrations below 20 mumol/L. (c) Inhibition of uridine (10 mumol/L) transport and degradation was observed after coperfusion with adenosine, deoxyadenosine, guanosine and deoxyguanosine.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver

Holstege

1991

Hepatology

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“…Although a higher labelling efficiency can be obtained using orotate [45], this precursor is taken up much more slowly and its half-life in the body of several hours [45-481 would be a substantial fraction of the total experimental period. The half-life of uridine in blood, however, is only 9 min [49] and, therefore, better suited for pulse-labelling.…”

Section: Discussionmentioning

confidence: 99%

Pyrimidine Nucleotide Biosynthesis and Turnover in Rat Skeletal Muscle and Liver

Rasenack

Nowack

Decker

1978

European Journal of Biochemistry

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Pyrimidine nucleotide biosynthesis in skeletal muscle of rat hindquarter was studied with a hemoglobin‐free constant‐pressure perfusion system. The functional competence of this preparation was monitored by determinations of oxygen consumption, lactate/pyruvate ratio, glucose uptake and its stimulation by insulin, ATP and creatine phosphate contents of the muscle, the energy charge and the release of aldolase and creatine phosphokinase into the perfusate. The time‐dependence of NaH14CO3 incorporation into the acid‐soluble uracil nucleotides of muscle tissue was measured and the rate of de novo biosynthesis calculated to be 2.7 μmol×kg‐1×h‐1. The half‐life of the uracil nucleotides of skeletal muscle in vivo was estimated by pulse‐labelling with [2‐14C]uridine and measuring the decrease of their specific radioactivity. It was found to be 19 h, corresponding to a turnover rate of the acid‐soluble uracil nucleotides of 5 μmol×kg‐1×h‐1. The influence of alimentary pyrimidines on uracil nucleotide biosynthesis in the perfused muscle was also investigated. In animals kept on a uridine‐free diet for 7 days, the incorporation rate of labelled bicarbonate into acid‐soluble uracil 5′‐nucleotides was 30% higher than in controls fed a commercial laboratory chow. The half‐life in vivo of the acid‐soluble uracil nucleotides of rat liver was estimated from the decrease of their specific radioactivity following a [2‐14C]uridine pulse. It was found to be 15 h, corresponding to a turnover rate of about 80 μmol×kg‐1×h‐1.

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“…Indeed, more than 90% of the circulating uridine is catabolized in a single pass through the liver by the activity of hepatic uridine phosphorylase (UP, EC 2.4.2.3), while constant amounts of uridine are synthesized de novo and released into the hepatic vein blood [28,29]. Less than 2% of the uridine metabolized by the liver is salvaged and recovered in the uracil nucleotide pool in tissues of whole animals [27,[30][31][32], perfused rat liver [6,13], or isolated liver cells [31]. The remainder is rapidly catabolized to products beyond uracil in the pyrimidine catabolic pathway [13,28,33].…”

Section: Introductionmentioning

confidence: 99%

Potent combination therapy for human breast tumors with high doses of 5-fluorouracil: remission and lack of host toxicity

Safarjalani

Rais²,

Naguib³

et al. 2012

Cancer Chemother Pharmacol

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In-vivo-Untersuchungen zur Metabolisierung der Pyrimidinnucleoside

Cited by 17 publications

References 3 publications

Facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver

Facilitated diffusion and sodium-dependent transport of purine and pyrimidine nucleosides in rat liver

Pyrimidine Nucleotide Biosynthesis and Turnover in Rat Skeletal Muscle and Liver

Potent combination therapy for human breast tumors with high doses of 5-fluorouracil: remission and lack of host toxicity

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