Lidocaine inhibits choline uptake and phosphatidylcholine biosynthesis in human leukemic monocyte-like U937 cells

1994 ◽  
Vol 12 (2) ◽  
pp. 89-98 ◽  
Author(s):  
Arthur J. Chu ◽  
Jack M. Lee
Keyword(s):  
Choline Uptake ◽  
U937 Cells ◽  
Phosphatidylcholine Biosynthesis

scholarly journals Effects of fasting on phosphatidylcholine biosynthesis in hamster liver: regulation of cholinephosphotransferase activity by endogenous argininosuccinate

1993 ◽  
Vol 289 (3) ◽  
pp. 727-733 ◽  
Author(s):  
K M O ◽  
P C Choy
Keyword(s):  
Enzyme Activity ◽  
Substantial Decrease ◽  
Compensatory Mechanism ◽  
Choline Uptake ◽  
Endogenous Inhibitor ◽  
Short Term ◽  
Phosphatidylcholine Biosynthesis ◽  
Choline Phosphotransferase ◽  
Pool Sizes

The control of phosphatidylcholine biosynthesis in the hamster liver was examined. Livers of hamsters fasted for 24 and 48 h were perfused with labelled choline. Under both fasting conditions, the incorporation of labelled choline into phosphatidylcholine was reduced. After 48 h of fasting, the 52% reduction in phosphatidylcholine biosynthesis was caused by changes in several factors including a diminishing rate of choline uptake and severe reductions in the pool sizes of ATP and CTP (to 33-37% control values) which resulted in a decrease in the pools of choline-containing metabolites. The activation of cytidylyltransferase after 48 h of fasting might be regarded as a compensatory mechanism for the maintenance of phosphatidylcholine biosynthesis. After 24 h of fasting, a 25% reduction in phosphatidylcholine biosynthesis was observed. The ATP and CTP levels were decreased but the reduction was not severe enough to affect the choline uptake or the labelling of the phosphocholine fraction. The activities of the cytidylyltransferase remained unchanged but an accumulation of labelled CDP-choline was detected. Although choline-phosphotransferase activity was not changed in the microsomes, the enzyme activity was attenuated in the postmitochondrial fraction. Further analysis revealed that cholinephosphotransferase in the liver was inhibited by an endogenous inhibitor in the cytosol which was later identified as argininosuccinate. The level of argininosuccinate was elevated during fasting and the change quantitatively accounted for the attenuation of cholinephosphotransferase activity. The inhibition of choline-phosphotransferase by argininosuccinate, coupled with a substantial decrease in the diacylglycerol level, would provide the hamster liver with an immediate mechanism for the transient modulation of phosphatidylcholine biosynthesis during short-term fasting.

Effects of amino acids and ethanolamine on choline uptake and phosphatidylcholine biosynthesis in baby hamster kidney-21 cells

1992 ◽  
Vol 70 (12) ◽  
pp. 1319-1324 ◽  
Author(s):  
Xiliang Zha ◽  
Francis T. Jay ◽  
Patrick C. Choy
Keyword(s):  
Amino Acids ◽  
Culture Media ◽  
Specific Radioactivity ◽  
Kinetic Studies ◽  
Choline Uptake ◽  
Dependent Manner ◽  
Baby Hamster Kidney ◽  
Concentration Dependent Manner ◽  
Cell Culture Media ◽  
Phosphatidylcholine Biosynthesis

The effects of amino acids and ethanolamine on choline uptake and phosphatidylcholine biosynthesis in baby hamster kidney (BHK-21) cells were investigated. The cells were incubated with labelled choline in the presence of an amino acid or ethanolamine. The uptake of labelled choline was noncompetitively inhibited by amino acids. Glycine, L-alanine, L-serine, L-leucine, L-aspartate, and L-arginine were effective inhibitors and a maximum of 22% inhibition of choline uptake was obtained with 5 mM glycine. Analyses of the labellings in the choline-containing metabolites revealed that the conversion of choline to CDP-choline and subsequently phosphatidylcholine was not affected by the presence of amino acids. The uptake of choline was also inhibited by ethanolamine in a concentration-dependent manner. Kinetic studies on the uptake of choline indicated that the inhibition by ethanolamine was competitive in nature. Although ethanolamine is a potent inhibitor of choline kinase, analyses of the labellings in the choline-containing metabolites indicated that the conversion of choline to phosphocholine was not affected in the cells incubated with ethanolamine. Ethanolamine did not change the pool sizes of phosphocholine and CDP-choline. Based on the specific radioactivity of CDP-choline and the labelling of phosphatidylcholine, the rates of phosphatidylcholine biosynthesis were not significantly different between the control and the ethanolamine-treated cells. In view of the concentrations of amino acids (millimolar) and ethanolamine (micromolar) in most cell culture media, it appeared that only amino acids were important metabolites for the regulation of choline uptake in BHK-21 cells. We conclude that both amino acids and ethanolamine have no direct effect on the biosynthesis of phosphatidylcholine.Key words: choline uptake, phosphatidylcholine biosynthesis, amino acids, ethanolamine, BHK-21 cells.

Effect of amino acids on choline uptake and phosphatidylcholine biosynthesis in the isolated hamster heart

1988 ◽  
Vol 66 (5) ◽  
pp. 418-424 ◽  
Author(s):  
Grant M. Hatch ◽  
Willem K. Stevens ◽  
Patrick C. Choy
Keyword(s):  
Amino Acids ◽  
Direct Interaction ◽  
Choline Uptake ◽  
Choline Transport ◽  
Neutral Amino Acids ◽  
Acidic Amino Acids ◽  
Phosphatidylcholine Biosynthesis ◽  
Concentration Threshold ◽  
Hamster Heart ◽  
Dose Dependent

Choline uptake by the hamster heart has been shown to be enhanced by exogenous glycine. In this study, the effect of neutral, basic, and acidic amino acids on choline uptake was assessed. Hamster hearts were perfused with labelled choline, and in the presence of L-alanine, L-serine, or L-phenylalanine (≥0.1 mM), choline uptake was enhanced 20–38%. L-Arginine, L-lysine, L-aspartate, and L-glutamate did not influence choline uptake. The rate of phosphatidylcholine biosynthesis was unaffected by all amino acids tested. Enhancement of choline uptake by neutral amino acids was not additive or dose dependent but required a concentration threshold. The enhancement of choline uptake by neutral amino acids was not influenced by preperfusion with the same amino acid. Exogenous choline had no effect on the uptake of amino acids. We postulate that choline and the neutral amino acids are not cotransported and modulation of choline uptake is facilitated by direct interaction of the neutral amino acids with the choline transport system.

The effect of amino acids on choline uptake and phosphatidylcholine biosynthesis in mammalian hearts

Lipids ◽  
1992 ◽  
Vol 27 (6) ◽  
pp. 466-469 ◽  
Author(s):  
Monroe Chan ◽  
O Karmin ◽  
Adrian S. Man ◽  
Patrick C. Choy
Keyword(s):  
Amino Acids ◽  
Choline Uptake ◽  
Phosphatidylcholine Biosynthesis

scholarly journals Metabolism, mitochondrial uptake and toxicity of 2′,3′-dideoxycytidine

1999 ◽  
Vol 344 (3) ◽  
pp. 915-920 ◽  
Author(s):  
Luigia ROSSI ◽  
Sonja SERAFINI ◽  
Giuditta F. SCHIAVANO ◽  
Anna CASABIANCA ◽  
Giuliana VALLANTI ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Human Cells ◽  
Deoxycytidine Kinase ◽  
Choline Uptake ◽  
Dependent Manner ◽  
U937 Cells ◽  
Mitochondrial Toxicity ◽  
Concentration Dependent Manner ◽  
Free System ◽  
Phosphocholine Cytidylyltransferase

2ʹ,3ʹ-Dideoxycytidine (ddCyd) is a prescription anti-retroviral drug that causes mitochondrial toxicity and peripheral neuropathy. ddCyd is actively phosphorylated by cytosolic deoxycytidine kinase and nucleoside (di)phosphate kinase to the 5ʹ-triphosphate derivative. However, 2ʹ,3ʹ-dideoxycytidine 5ʹ-diphosphocholine (ddCDP-choline) was also found in human cells incubated with ddCyd. In this paper we show that ddCDP-choline is produced from dideoxyCTP (ddCTP) and phosphocholine by phosphocholine cytidylyltransferase. dCTP and CTP appear to activate this synthesis in a concentration-dependent manner. Although ddCTP and ddCDP-choline can both enter the mitochondria, ddCDP-choline uptake is more efficient than ddCTP uptake. These data suggest that ddCDP- choline is the ddCyd metabolite that is probably responsible for mitochondrial toxicity. The uptake of ddCTP and ddCDP-choline by mitochondria is inhibited by 3.0 mM L-carnitine in the cell-free system investigated; when added to U937 cells grown in the presence of 0.25 μM ddCyd, 3.0 mM L-carnitine partially abrogated the mitochondrial toxicity of ddCyd.

scholarly journals Antagonism of phorbol-ester-stimulated phosphatidylcholine biosynthesis by the phospholipid analogue hexadecylphosphocholine

1993 ◽  
Vol 291 (2) ◽  
pp. 561-567 ◽  
Author(s):  
T Wieder ◽  
C C Geilen ◽  
W Reutter
Keyword(s):  
Cell Lines ◽  
Hela Cells ◽  
Mdck Cells ◽  
Fold Increase ◽  
Choline Uptake ◽  
Choline Incorporation ◽  
Contrast Enhanced ◽  
Phosphatidylcholine Biosynthesis ◽  
Membrane Bound ◽  
Stimulation Of

The antagonization of phorbol 12-myristate 13-acetate (PMA)-stimulated phosphatidylcholine (PtdCho) biosynthesis by the phospholipid analogue hexadecylphosphocholine (HePC) in MDCK cells was investigated and compared with the corresponding influence in HeLa cells. In both cell lines, PMA-stimulated PtdCho biosynthesis was antagonized by 50 microM HePC. However, subsequent experiments provided evidence that PMA enhances PtdCho biosynthesis by at least two mechanisms: (i) by stimulation of choline uptake and (ii) by translocation of CTP:choline phosphate cytidylyltransferase to membranes. In MDCK cells, 5 nM PMA caused a 4-fold increase in [methyl-3H]choline incorporation into PtdCho, which was paralleled by an approx. 2-fold stimulation of choline uptake. These data indicate that choline uptake might play an important role in the regulation of PtdCho biosynthesis in this cell line, especially since we could not detect any significant increase in membrane-bound cytidyltransferase activity in PMA-treated MDCK cells. In contrast, enhanced PtdCho biosynthesis in HeLa cells is achieved by a 2-fold increase in particulate cytidylyltransferase activity after PMA stimulation. Translocation of cytidylyltransferase from the cytosol to membranes is therefore important in HeLa cells. Nevertheless, in both cell lines, the main target of HePC seems to be the translocation process. In MDCK cells, addition of 50 microM HePC decreases membrane-bound cytidylyltransferase activity by about 45%, compared with control cells and PMA-treated cells. In HeLa cells, PMA-induced translocation of cytidylyltransferase to membranes is totally abolished by HePC.

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