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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
1990-10-26
|
| pubmed:abstractText |
The metabolism of 2-deoxy-2-fluoro-D-galactose (dGalF) was studied in rodents using HPLC, enzymatic methods, and 19F-NMR spectroscopy in vivo and in vitro. The liver took up the major part of the administered dose of the 14C-labeled D-galactose analog. This was confirmed in vivo by use of the 18F-labeled sugar (1.5 mCi/kg; 25 mumol/kg) and examination by positron emission tomography. After a dose of 1 mmol/kg, dGalF-1-phosphate accumulated rapidly (5.3 +/- 0.4 mmol/kg after 30 min), followed by formation of UDP-dGalF and UDP-2-deoxy-2-fluoro-D-glucose (0.7 +/- 0.1 and 1.8 +/- 0.1 mmol/kg, respectively, after 5 hr). Good quantitative agreement was obtained between the measurements by HPLC and enzymatic analyses and by 19F-NMR. The noninvasive in vivo 19F-NMR technique is particularly advantageous, since it allows the simultaneous analysis of all dGalF metabolites. The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepatic UTP, UDP-glucose, and UDP-galactose. The UTP content was decreased to 11 +/- 6% of normal within 15 min after administration of dGalF at a dose of 1 mmol/kg. The UTP-depleting action was minimal, however, at a dose of 25 mumol/kg or less, indicating that interference in uridylate metabolism will be negligible at the doses required for positron emission tomography of the liver using the 18F-labeled compound. At higher doses the UTP deficiency induced by dGalF may be useful in the chemotherapy of D-galactose-metabolizing tumors such as hepatocellular carcinoma. At moderate doses of dGalF, 19F-NMR spectroscopy in vivo or in vitro could be used to pinpoint defects of the enzymes that cause galactosemia, i.e. of galactokinase, uridyltransferase, or 4-epimerase.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-deoxy-2-fluorogalactose,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorine,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorine Radioisotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Fucose,
http://linkedlifedata.com/resource/pubmed/chemical/Galactose,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen,
http://linkedlifedata.com/resource/pubmed/chemical/Uridine Triphosphate
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| pubmed:status |
MEDLINE
|
| pubmed:issn |
0065-2571
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
30
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
231-42
|
| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:2403033-Animals,
pubmed-meshheading:2403033-Brain,
pubmed-meshheading:2403033-Chromatography, High Pressure Liquid,
pubmed-meshheading:2403033-Female,
pubmed-meshheading:2403033-Fluorine,
pubmed-meshheading:2403033-Fluorine Radioisotopes,
pubmed-meshheading:2403033-Fucose,
pubmed-meshheading:2403033-Galactose,
pubmed-meshheading:2403033-Hydrogen,
pubmed-meshheading:2403033-Kidney,
pubmed-meshheading:2403033-Kinetics,
pubmed-meshheading:2403033-Liver,
pubmed-meshheading:2403033-Magnetic Resonance Spectroscopy,
pubmed-meshheading:2403033-Mice,
pubmed-meshheading:2403033-Mice, Inbred Strains,
pubmed-meshheading:2403033-Rats,
pubmed-meshheading:2403033-Rats, Inbred Strains,
pubmed-meshheading:2403033-Tomography, Emission-Computed,
pubmed-meshheading:2403033-Uridine Triphosphate,
pubmed-meshheading:2403033-Urinary Bladder
|
| pubmed:year |
1990
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| pubmed:articleTitle |
In vivo metabolism and UTP-depleting action of 2-deoxy-2-fluoro-D-galactose.
|
| pubmed:affiliation |
Deutsches Krebsforschungszentrum, Heidelberg, F.R.G.
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| pubmed:publicationType |
Journal Article
|