Document Detail

Specificity of pyrimidine nucleoside phosphorylases and the phosphorolysis of 5-fluoro-2'-deoxyuridine.
MedLine Citation:
PMID:  6451286     Owner:  NLM     Status:  MEDLINE    
Isoelectric focusing and studies with 1-(2'-deoxy-beta-D-glucopyranosyl)thymine (GPT), a specific inhibitor of uridine phosphorylase activity, were used to determine the substrate specificities of mammalian pyrimidine nucleoside phosphorylases and their cleavage of 5-fluoro-2'-deoxyuridine (FdUrd). Isoelectric focusing profiles for the cytosol fractions from Ehrlich ascites cells and from Novikoff hepatoma cells each consisted essentially of one peak of nucleoside phosphorylase activity [isoelectric points (pl) 5.4 and 5.8, respectively] that cleaved both uridine and thymidine (dThd), as well as FdUrd. By contrast, cytosol fractions from HeLa (S3) cells, mouse liver, and normal human leukocytes each exhibited a major peak of activity (pl 4.6, 6.5, and 4.9, respectively) that cleaved only dThd and FdUrd, while mouse liver exhibited a second peak (pl 5.2) that cleaved primarily uridine. To distinguish clearly between (a) uridine phosphorylases that cleave primarily uridine and that are inhibited by GPT and (b)dThd phosphorylases that cleave only deoxynucleosides and that are not inhibited by GPT, we propose the term "uridine-deoxyuridine phosphorylases" to define those pyrimidine nucleoside phosphorylases that cleave both uridine and dThd and that are inhibited by GPT. On the basis of this definition and studies with GPT in nonfocused cytosol preparations, we conclude that FdUrd is cleaved to 5-fluorouracil by uridine-deoxyuridine phosphorylase activity in Ehrlich ascites cells and in Novikoff hepatoma cells, and by dThd phosphorylases in mouse liver, in normal human leukocytes, and in HeLa (S3) cells.
P W Woodman; A M Sarrif; C Heidelberger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  40     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1980 Mar 
Date Detail:
Created Date:  1981-05-26     Completed Date:  1981-05-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  507-11     Citation Subset:  IM    
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MeSH Terms
Carcinoma, Ehrlich Tumor / enzymology
Cells, Cultured
Floxuridine / metabolism*
Hela Cells / enzymology
Isoelectric Point
Leukocytes / enzymology
Liver / enzymology
Liver Neoplasms, Experimental / enzymology
Pentosyltransferases / metabolism*
Pyrimidine Nucleosides / metabolism
Substrate Specificity
Thymidine / analogs & derivatives,  pharmacology
Thymidine Phosphorylase / metabolism
Uridine Phosphorylase / antagonists & inhibitors,  metabolism
Grant Support
Reg. No./Substance:
0/Pyrimidine Nucleosides; 50-89-5/Thymidine; 50-91-9/Floxuridine; 5116-45-0/1-(2'-deoxy-beta-D-glucopyranosyl)thymine; EC 2.4.2.-/Pentosyltransferases; EC phosphorylase; EC Phosphorylase; EC Phosphorylase

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