|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 7, 5453-5459, February 15, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Pharmacology, Yale University School of
Medicine, New Haven, Connecticut 06520
D-Nucleoside analogs, which are
in the natural configuration, as well as the L-nucleoside
analogs, are clinically relevant antiviral and anticancer agents.
Metabolism of L-nucleoside analog diphosphates to the
triphosphates, however, remains unexplored. Studies with recombinant
nm23-H1 and -H2 isoforms indicated that L-nucleoside analog
diphosphates were not phosphorylated by their nucleoside diphosphate
kinase (NDPK) activity. Therefore, roles of creatine kinase,
3-phosphoglycerate kinase, and pyruvate kinase were evaluated using
preparations from commercial sources and human HepG2 cells.
Phosphorylation of L-OddC, L-SddC,
L-Fd4C, L-FMAU, and L-ddC were
compared with D-deoxynucleoside analogs, AraC, dFdC, and
D-FMAU, and D-dideoxynucleoside analogs, ddC
and d4T. Results based on preparations from HepG2 cells showed that L-nucleoside analog diphosphates were selectively
phosphorylated by 3-phosphoglycerate kinase, whereas,
D-deoxynucleoside analog diphosphates were phosphorylated
by NDPK. Interestingly, ddCDP and d4TDP were substrates for creatine
kinase, but were not phosphorylated by NDPK. In conclusion, it is
proposed that specificity of the phosphorylating enzymes toward the
nucleoside analog diphosphates is dependent on the configuration of the
analog (L or D) and the presence or absence of
3'-hydroxyl group in the sugar moiety. The enzymatic process of
phosphorylation of L- and D-nucleoside analog
diphosphates is different in cells.
Phosphorylation of Pyrimidine Deoxynucleoside Analog
Diphosphates
SELECTIVE PHOSPHORYLATION OF L-NUCLEOSIDE
ANALOG DIPHOSPHATES BY 3-PHOSPHOGLYCERATE KINASE*
,
*
This work was supported in part by Grants CA 63477 and AI
38204 from the National Institutes of Health.
Present address: Molecular Staging, 300 George St., 7th Floor, New
Haven, CT 06511.
§
A fellow of the National Foundation for Cancer Research. To whom
correspondence should be addressed: Dept. of Pharmacology, Yale
University School of Medicine, New Haven, CT 06520. Tel.: 203-785-7120;
Fax: 203-785-7129; E-mail: cheng.lab@yale.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  W. Lam, S. Bussom, and Y.-C. Cheng Effect of hypoxia on the expression of phosphoglycerate kinase and antitumor activity of troxacitabine and gemcitabine in non-small cell lung carcinoma Mol. Cancer Ther., February 1, 2009; 8(2): 415 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Ray, J. E. Vela, C. G. Boojamra, L. Zhang, H. Hui, C. Callebaut, K. Stray, K.-Y. Lin, Y. Gao, R. L. Mackman, et al. Intracellular Metabolism of the Nucleotide Prodrug GS-9131, a Potent Anti-Human Immunodeficiency Virus Agent Antimicrob. Agents Chemother., February 1, 2008; 52(2): 648 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Lam, C.-H. Leung, S. Bussom, and Y.-C. Cheng The Impact of Hypoxic Treatment on the Expression of Phosphoglycerate Kinase and the Cytotoxicity of Troxacitabine and Gemcitabine Mol. Pharmacol., September 1, 2007; 72(3): 536 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Hernandez-Santiago, J. S. Mathew, K. L. Rapp, J. P. Grier, and R. F. Schinazi Antiviral and Cellular Metabolism Interactions between Dexelvucitabine and Lamivudine Antimicrob. Agents Chemother., June 1, 2007; 51(6): 2130 - 2135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Hsu, R. Hu, G. E. Dutschman, G. Yang, P. Krishnan, H. Tanaka, M. Baba, and Y.-C. Cheng Comparison of the Phosphorylation of 4'-Ethynyl 2',3'-Dihydro-3'-Deoxythymidine with That of Other Anti-Human Immunodeficiency Virus Thymidine Analogs Antimicrob. Agents Chemother., May 1, 2007; 51(5): 1687 - 1693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Murakami, H. Bao, M. Ramesh, T. R. McBrayer, T. Whitaker, H. M. Micolochick Steuer, R. F. Schinazi, L. J. Stuyver, A. Obikhod, M. J. Otto, et al. Mechanism of Activation of {beta}-D-2'-Deoxy-2'-Fluoro-2'-C-Methylcytidine and Inhibition of Hepatitis C Virus NS5B RNA Polymerase Antimicrob. Agents Chemother., February 1, 2007; 51(2): 503 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhou, J. H. Rodman, P. M. Flynn, B. L. Robbins, C. K. Wilcox, and D. Z. D'Argenio Model for intracellular Lamivudine metabolism in peripheral blood mononuclear cells ex vivo and in human immunodeficiency virus type 1-infected adolescents. Antimicrob. Agents Chemother., August 1, 2006; 50(8): 2686 - 2694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Lam, S.-Y. Park, C.-H. Leung, and Y.-C. Cheng Apurinic/Apyrimidinic Endonuclease-1 Protein Level Is Associated with the Cytotoxicity of L-Configuration Deoxycytidine Analogs (Troxacitabine and beta-L-2',3'-Dideoxy-2',3'-didehydro-5-fluorocytidine) but Not D-Configuration Deoxycytidine Analogs (Gemcitabine and beta-D-Arabinofuranosylcytosine) Mol. Pharmacol., May 1, 2006; 69(5): 1607 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Jordheim, O. Guittet, M. Lepoivre, C. M. Galmarini, and C. Dumontet Increased expression of the large subunit of ribonucleotide reductase is involved in resistance to gemcitabine in human mammary adenocarcinoma cells Mol. Cancer Ther., August 1, 2005; 4(8): 1268 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Hsu, J.-Y. Liou, G. E. Dutschman, and Y.-C. Cheng Phosphorylation of Cytidine, Deoxycytidine, and Their Analog Monophosphates by Human UMP/CMP Kinase Is Differentially Regulated by ATP and Magnesium Mol. Pharmacol., March 1, 2005; 67(3): 806 - 814. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Lapointe, R. Letourneau, W. Steward, R. E. Hawkins, G. Batist, M. Vincent, R. Whittom, M. Eatock, J. Jolivet, and M. Moore Phase II study of troxacitabine in chemotherapy-naive patients with advanced cancer of the pancreas: Gastrointestinal tumors Ann. Onc., February 1, 2005; 16(2): 289 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Gourdeau, L. Leblond, B. Hamelin, K. Dong, F. Ouellet, C. Boudreau, D. Custeau, A. Richard, M.-J. Gilbert, and J. Jolivet Species Differences in Troxacitabine Pharmacokinetics and Pharmacodynamics: Implications for Clinical Development Clin. Cancer Res., November 15, 2004; 10(22): 7692 - 7702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Jordheim, E. Cros, M.-H. Gouy, C. M. Galmarini, S. Peyrottes, J. Mackey, C. Perigaud, and C. Dumontet Characterization of a Gemcitabine-Resistant Murine Leukemic Cell Line: Reversion of In vitro Resistance by a Mononucleotide Prodrug Clin. Cancer Res., August 15, 2004; 10(16): 5614 - 5621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Krishnan, E. A. Gullen, W. Lam, G. E. Dutschman, S. P. Grill, and Y.-c. Cheng Novel Role of 3-Phosphoglycerate Kinase, a Glycolytic Enzyme, in the Activation of L-Nucleoside Analogs, a New Class of Anticancer and Antiviral Agents J. Biol. Chem., September 19, 2003; 278(38): 36726 - 36732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Seigneres, P. Martin, B. Werle, O. Schorr, C. Jamard, L. Rimsky, C. Trepo, and F. Zoulim Effects of Pyrimidine and Purine Analog Combinations in the Duck Hepatitis B Virus Infection Model Antimicrob. Agents Chemother., June 1, 2003; 47(6): 1842 - 1852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-Y. Liou, P. Krishnan, C.-C. Hsieh, G. E. Dutschman, and Y.-c. Cheng Assessment of the Effect of Phosphorylated Metabolites of Anti-Human Immunodeficiency Virus and Anti-Hepatitis B Virus Pyrimidine Analogs on the Behavior of Human Deoxycytidylate Deaminase Mol. Pharmacol., January 1, 2003; 63(1): 105 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Krishnan, J.-Y. Liou, and Y.-C. Cheng Phosphorylation of Pyrimidine L-Deoxynucleoside Analog Diphosphates. KINETICS OF PHOSPHORYLATION AND DEPHOSPHORYLATION OF NUCLEOSIDE ANALOG DIPHOSPHATES AND TRIPHOSPHATES BY 3-PHOSPHOGLYCERATE KINASE J. Biol. Chem., August 23, 2002; 277(35): 31593 - 31600. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |