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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1990-8-13
|
| pubmed:abstractText |
The synthetic D-galactose analog 2-deoxy-2-fluoro-D-galactose (dGalF) offers unique advantages for studies of the D-galactose pathway by non-invasive techniques using 19F-NMR spectroscopy or positron emission from the 18F-labeled compound. The metabolism of 2-deoxy-2-fluoro-D-galactose was studied in rodents using the unlabeled, the 18F-labeled, and the 14C-labeled D-galactose analog. Analyses for the metabolites of 2-deoxy-2-fluoro-D-galactose were performed by HPLC, enzymatic methods, and 19F-NMR spectroscopy in vivo and in vitro. The metabolism of 2-deoxy-2-fluoro-D-galactose was most active in the liver which took up the major part of the administered dose of the 14C-labeled D-galactose analog, but renal excretion was also pronounced. This was confirmed by in vivo scanning of the rat using the 18F-labeled sugar (1.5 microCi/g; 25 nmol/g) and examination by positron-emission tomography and gamma camera. The dose dependence of the levels of the hepatic metabolites of 2-deoxy-2-fluoro-D-galactose was investigated for doses between 25 nmol/g body mass and 1 mumols/g body mass. After 1 h, the major part of the acid-soluble uracil nucleotides consisted of UDP-2-deoxy-2-fluoro-D-hexoses when the dose was at least 0.1 mumols/g. With higher doses, 2-deoxy-2-fluoro-D-galactose 1-phosphate became the predominant initial metabolite. After a dose of 1 mumols/g 2-deoxy-2-fluoro-D-galactose 1-phosphate accumulated rapidly (5.3 +/- 0.4 mumols/g liver after 30 min) followed by the formation of UDP-2-deoxy-2-fluoro-D-galactose and UDP-2-deoxy-2-fluoro-D-glucose (0.7 +/- 0.1 mumols/g and 1.8 +/- 0.1 mumols/g, respectively, after 5 h). 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 2-deoxy-2-fluoro-D-galactose at a dose of 1 mumols/g. The UTP-depleting action was minimal, however, at a dose of 25 nmols/g or less, indicating that interference in uridylate metabolism would 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 2-deoxy-2-fluoro-D-galactose could be useful in the chemotherapy of D-galactose-metabolizing tumors such as hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0014-2956
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
31
|
| pubmed:volume |
190
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
11-9
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| pubmed:dateRevised |
2007-7-23
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| pubmed:meshHeading |
pubmed-meshheading:2114284-Animals,
pubmed-meshheading:2114284-Chromatography, High Pressure Liquid,
pubmed-meshheading:2114284-Female,
pubmed-meshheading:2114284-Fucose,
pubmed-meshheading:2114284-Galactose,
pubmed-meshheading:2114284-Gamma Cameras,
pubmed-meshheading:2114284-Liver,
pubmed-meshheading:2114284-Magnetic Resonance Spectroscopy,
pubmed-meshheading:2114284-Mice,
pubmed-meshheading:2114284-Nucleotides,
pubmed-meshheading:2114284-Rats,
pubmed-meshheading:2114284-Rats, Inbred Strains,
pubmed-meshheading:2114284-Tissue Distribution,
pubmed-meshheading:2114284-Tomography, Emission-Computed,
pubmed-meshheading:2114284-Whole-Body Counting
|
| pubmed:year |
1990
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| pubmed:articleTitle |
Metabolism and actions of 2-deoxy-2-fluoro-D-galactose in vivo.
|
| pubmed:affiliation |
Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
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| pubmed:publicationType |
Journal Article
|