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

Rijcken, W R Pels; Overdijk, B.; Eijnden, Dirk H. van den; Ferwerda, W

doi:10.1042/bj2930207

Cited by 35 publications

(15 citation statements)

References 37 publications

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“…For UTP and the other uridine derivatives studied, this increase was much more pronounced than for the cytidine derivatives, irrespective of the use of either uridine or cytidine. This is in agreement with previous observations (Pels Rijcken et al, 1993). It shows that the synthesis of CTP is strictly regulated, probably by feedback inhibition.…”

Section: Resultssupporting

confidence: 94%

“…As part of our studies [see also Pels Rijcken et al (1990, 1993] processed during the subsequent transport to their final deson the latter mode of regulation, we determined the effect of tination. This process has appeared to be an essential prerequisite increases of the nucleotide-sugar pools in rat hepatocytes, as for obtaining biologically competent molecules at their proper brought about by pretreatment of the cells with uridine and location (Lodish, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…This process has appeared to be an essential prerequisite increases of the nucleotide-sugar pools in rat hepatocytes, as for obtaining biologically competent molecules at their proper brought about by pretreatment of the cells with uridine and location (Lodish, 1988). The sequence of events in the N-and 0 cytidine (Pels Rijcken et al, 1993) on the incorporation of glycosylation of proteins has been extensively studied (Kornfeld radioactive sugars into glycoconjugates. For that purpose we and Kornfeld, 1985;Schachter, 1986).…”

Section: Introductionmentioning

confidence: 99%

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The effect of increasing nucleotide-sugar concentrations on the incorporation of sugars into glycoconjugates in rat hepatocytes

Rijcken

Overdijk

Eijnden

et al. 1995

Biochemical Journal

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Treatment of rat hepatocytes with 0.5 mM concentrations ofThe latter increase did not result in an increased incorporation of uridine and cytidine results in increased cellular concentrations radioactivity into the glycoconjugates. It was estimated that, in of UTP, UDP-sugars and CTP, whereas that of CMP-Nuntreated cells, the ratio of radioactivity incorporated from acetylneuraminate remained unchanged [Pels Rijcken, Overdijk, [3H]glucosamine into glycoconjugate-bound N-acetylhexosamine Van den Eijnden and Ferwerda (1993) Biochem. J. 293,207-213]. and N-acetylneuraminate amounted to 2:3. In pretreated cells The incorporation of radioactivity from 3H-labelled sugars into this ratio changed to approx. 2: 1. Overall, the data show that the cell-associated and secreted glycoconjugate fraction was pretreatment resulted in an increased incorporation of N-acetylinfluenced by these altered cellular concentrations of the nucleohexosamine into cell-associated and secreted glycoconjugates, tides. For [3H]glucosamine, pretreatment with uridine resulted in accompanied by a reduction in sialylation. It was concluded that a reduction of the glycosylation in both fractions. Increases in an increased availability of UDP-N-acetylhexosamine caused the the secreted fractions were observed for fucose with both uridine increased incorporation of N-acetylhexosamine. The elevated and cytidine and for N-acetylglucosamine with uridine only. This study demonstrates that protein glycosylation can be acetylmannosamine, the specific radioactivity of CMP-N-acetylregulated at the level of the availability of the various nucleotideneuraminate showed an almost 2-fold increase on pretreatment.sugars in the Golgi lumen.

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Section: Resultssupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The effect of increasing nucleotide-sugar concentrations on the incorporation of sugars into glycoconjugates in rat hepatocytes

Rijcken

Overdijk

Eijnden

et al. 1995

Biochemical Journal

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“…In addition, with respect to the analysis of CHO cell extracts, similar proportions of nucleotide-sugars were reported to occur in rat hepatocytes. Pels Rijcken et al (1993) reported high concentrations of UDP-sugars (e.g., 2.96 nmol UDP-HexNAc/10 6 cells, 3.95 nmol UDP-Hex/10 6 cells) relative to CMP-Nacetylneuraminic acid (CMP-NeuAc) content (0.24 nmol/ 10 6 cells). It is interesting to compare the cellular content of nucleotide sugar substrates with that of the recombinant IFN-␥ glycoprotein.…”

Section: Discussionmentioning

confidence: 98%

Constraints on the transport and glycosylation of recombinant IFN-? in Chinese hamster ovary and insect cells

Hooker

Green

Baines

et al. 1999

Biotechnol. Bioeng.

109

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“…Endogenous nucleotides are recycled intracellularly (25,26) and intracellular metabolic activities appear to be compartmentalised (27) in a way which allows incoming exogenous precursors to be catabolised and replaced in a single hepatic transit by salvageable products of de novo synthesis (28). Most incoming nucleosides in portal venous blood are removed in a single passage (29,30).…”

Section: Role Of the Liver In Nucleotide Homeostasis In Vivomentioning

confidence: 99%

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1995

Liver

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A1 .ne and pyrimidine metabol for antiviral chemotherapy viral hepatitis Shaw T, Locarnini SA. Hepatic purine and pyrimidine metabolism: implications for antiviral chemotherapy of viral hepatitis. Liver 1995: 15: 169-184. 0 Munksgaard, 1995 Abstract: The use of nucleoside analogues as antiviral agents is expanding. For most nucleoside analogues, intracellular phosphorylation is the major prerequisite for activity. Antiviral activity may be limited by poor uptake, absence of appropriate activating enzymes, catabolism, and competition from endogenous nucleotides. Appreciation of these factors, which are species-, tissue-and cell-specific is important in the understanding of the pharmacology and toxicology of nucleoside analogues. The use of nucleoside analogues against the agents of viral hepatitis is inherently problematic for many reasons including active hepatic nucleoside catabolism, probable absence of virus-specific activating enzymes, competition from endogenous nucleotides synthesised de novo or derived from RNA turnover, and factors related to mitochondria1 toxicity. Despite these drawbacks, some nucleoside analogues have been found efficacious against hepatitis B virus and it is likely that as knowledge of their mechanism of action accumulates, their efficacy can be improved both by rational drug design and by use in combination with other drugs, including interferon.

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

Cited by 35 publications

References 37 publications

The effect of increasing nucleotide-sugar concentrations on the incorporation of sugars into glycoconjugates in rat hepatocytes

The effect of increasing nucleotide-sugar concentrations on the incorporation of sugars into glycoconjugates in rat hepatocytes

Constraints on the transport and glycosylation of recombinant IFN-? in Chinese hamster ovary and insect cells

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