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Determination of Dihydropyrimidine Dehydrogenase (DPD) in Fibroblasts of a DPD Deficient Pediatric Patient and Family Members using a Polyclonal Antibody to Human DPD

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Purine and Pyrimidine Metabolism in Man VIII

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 370))

Abstract

Dihydropyrimidine dehydrogenase (EC 1.3.1.2, DPD) is the initial rate-limiting enzyme in pyrimidine catabolism, which catalyzes the following reaction.

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References

  1. T. W. Traut, and S. Loechel, Pyrimidine catabolism: individual characterization of the three sequential enzymes with a new assay, Biochemistry 23:2533–2539 (1984).

    Article  PubMed  CAS  Google Scholar 

  2. F. Zafra, M.C. Aragon, F. Valdiviesco, and C. Gimenez, ß-Alanine transport into plasma membrane vesicles derived from rat brain synaptosomes, Neurochem. Res. 9: 695–707 (1984).

    Article  PubMed  CAS  Google Scholar 

  3. R.B. Diasio and B.E. Harris, Clinical pharmacology of 5-fluorouracil, Clin. Pharmacokinet. 16: 215–237, 1989.

    Article  PubMed  CAS  Google Scholar 

  4. G.C. Daher, B. E. Harris, and R.B. Diasio, Metabolism of pyrimidine analogues and their nucleosides, Pharmacol. Ther. 48:189–222 (1990).

    Article  PubMed  CAS  Google Scholar 

  5. G.D. Heggie, J.-P. Sommadossi, D.S. Cross, W.J. Huster, and R.B. Diasio, Clinical Pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile, Cancer Res. 47:2203–2206 (1987).

    PubMed  CAS  Google Scholar 

  6. B.E. Harris, R. Song, S.-J. Soong, and R.B. Diasio, Relationship between dihydropyrimidine dehydrogenase activity and plasma 5-fluorouracil levels with evidence for circadian variation of enzyme activity and plasma drug levels in cancer patients receiving 5-fluorouracil by protracted continuous infusion, Cancer Res. 50:197–201 (1990).

    PubMed  CAS  Google Scholar 

  7. R.A. Fleming, G. Milano, A. Thyss, M.-C. Etienne, N. Renee, M. Schneider, and F. Demard, Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients, Cancer Res. 52: 2899–2902 (1992).

    PubMed  CAS  Google Scholar 

  8. R. Zhang, Z. Lu, T. Liu, S.-J. Soong, and R.B. Diasio, Relationship between circadian-dependent toxicity of 5-fluorodeoxyuridine and circadian rhythms of pyrimidine enzymes; Possible relevance to fluoropyrimidine chemotherapy, Cancer Res. 53: 2816–2822 (1993).

    PubMed  CAS  Google Scholar 

  9. M. Tuchman, J.S. Stoeckeler, D.T. Kiang, R.F. O’Dea, M.L. Rammaraine, and B.L. Mirkin, Familial pyrimidinemia and pyrimidinuria associated with severe fluorouracil toxicity, New Engl. J. Med. 313:245–249 (1985).

    Article  PubMed  CAS  Google Scholar 

  10. R.B. Diasio, T.L. Beavers, and J.T. Carpenter, Familial deficiency of dihydropyrimidine dehydrogenase, J. Clin. Invest. 81:47–51 (1988).

    Article  PubMed  CAS  Google Scholar 

  11. B.E. Harris, J.T. Carpenter, and R.B. Diasio, Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency: a potentially more common pharmacogenetic syndrome, Cancer 68: 499–501 (1991).

    Article  PubMed  CAS  Google Scholar 

  12. A.P. Lyss, R.C. Lilenbaum, B.E. Harries, and R.B. Diasio, Severe 5-fluorouracil toxicity in a patient with decreased dihydropyrimidine dehydrogenase activity, Cancer Invest. 11: 239–240 (1993).

    Article  PubMed  CAS  Google Scholar 

  13. Z. Lu, R. Zhang, R.B. Diasio, Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy, Cancer Res. 53: 5433–5438 (1993).

    PubMed  CAS  Google Scholar 

  14. P. Houyau, C. Gay, E. Chatelut, P. Canal, H. Roche, and G. Milano, Severe fluorouracil toxicity in a patient with dihydropyrimidine dehydrogenase deficiency, J. Nat. Cancer Inst. 85: 1602–1603 (1993).

    Article  PubMed  CAS  Google Scholar 

  15. K. Ward, M.J. Henderson, H.A. Simmonds, J.A. Duley, and P.M. Davies, Dihydropyrimidinuria presenting in childhood with severe developmental retardation, in: “Molecular Genetics, Biochemistry and Clinical Aspects of Inherited Disorders of Purine and Pyrimidine Metabolism”, U. Gresser, ed., pp. 165–167, Springer-Verlag, Berlin Heidelberg (1993).

    Chapter  Google Scholar 

  16. M. Brocksted, C. Jakobs, L.M.E. Smith, A.H. van Gennip, and R. Berger, A new case of dihydropyrimidine dehydrogenase deficiency, J. Inher. Metab. Dis. 13: 121–124 (1990).

    Article  Google Scholar 

  17. Z. Lu, R. Zhang, and R. B Diasio, Purification and characterization of dihydropyrimidine dehydrogenase from human liver, J. Biol. Chem. 267:17102–17109 (1992).

    PubMed  CAS  Google Scholar 

  18. R. Zhang, Z. Lu, and R. B. Diasio, Quantitation of dihydropyrimidine dehydrogenase (DPD) using a polyclonal antibody to human liver DPD, Proc. Am. Assoc. Cancer. Res. 35:200 (1994).

    Google Scholar 

  19. Z. Lu, R. Zhang, and Diasio, R. B. Genetic polymorphism of dihydropyrimidine dehydrogenase (DPD), the key enzyme in 5-fluorouracil (FUra) catabolism, Clin. Pharm. Ther. 54: 180 (1994).

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pharmacology, Division of Clinical Pharmacology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Al, 35294, USA

    R. B. Diasio, Z. Lu & R. Zhang

  2. Laboratory of Metabolic Diseases and Procreation, Academic Medical Center, Amsterdam, Netherlands

    A. B. P. Van Kuilenburg, H. Van Lenthe, H. D. Bakker & A. H. Van Gennip

Authors
  1. R. B. Diasio
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  2. A. B. P. Van Kuilenburg
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  3. Z. Lu
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  4. R. Zhang
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  5. H. Van Lenthe
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  6. H. D. Bakker
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  7. A. H. Van Gennip
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Editor information

Editors and Affiliations

  1. Indiana University School of Medicine, Indianapolis, Indiana, USA

    Amrik Sahota

  2. Indiana University, Bloomington, Indiana, USA

    Milton W. Taylor

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© 1995 Springer Science+Business Media New York

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Diasio, R.B. et al. (1995). Determination of Dihydropyrimidine Dehydrogenase (DPD) in Fibroblasts of a DPD Deficient Pediatric Patient and Family Members using a Polyclonal Antibody to Human DPD. In: Sahota, A., Taylor, M.W. (eds) Purine and Pyrimidine Metabolism in Man VIII. Advances in Experimental Medicine and Biology, vol 370. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2584-4_2

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  • DOI: https://doi.org/10.1007/978-1-4615-2584-4_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6105-3

  • Online ISBN: 978-1-4615-2584-4

  • eBook Packages: Springer Book Archive

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