Dihydroorotate dehydrogenase - Profile of a novel target for antiproliferative and immunosuppressive drugs

Advances in Experimental Medicine and Biology

Volumn 431, Issue , 1998, Pages 507-513

  Löffler, Monika ^a   Grein, Klaus ^a   Knecht, Wolfgang ^a   Klein, Astrid ^a   Bergjohann, Ute ^a  

^a PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 NAPHTHOQUINONE DERIVATIVE; ANTIBODY; ATOVAQUONE; BREQUINAR; CAD PROTEIN; DIHYDROOROTATE DEHYDROGENASE; DNA; FLAVINE MONONUCLEOTIDE; IMMUNOGLOBULIN; ISOXAZOLE DERIVATIVE; LAPACHOL; LAWSONE; LEFLUNOMIDE; NUCLEIC ACID; OROTIC ACID; OXYGEN; PIRAZOFURIN; RNA; SUCCINATE DEHYDROGENASE; SYNTHETASE; TERIFLUNOMIDE;

CLINICAL TRIAL; CONFERENCE PAPER; DRUG BINDING; ENZYME ACTIVITY; ENZYME HISTOCHEMISTRY; GRAFT REJECTION; HUMAN; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RHEUMATOID ARTHRITIS;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; ENZYME INHIBITORS; HUMANS; IMMUNOGLOBULINS; IMMUNOSUPPRESSIVE AGENTS; MODELS, BIOLOGICAL; OXIDOREDUCTASES; OXIDOREDUCTASES ACTING ON CH-CH GROUP DONORS; PYRIMIDINES; RECOMBINANT PROTEINS;

EID: 0031807754     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-4615-5381-6_99     Document Type: Article

References (23)

1. Jones, M.E. (1980) Pyrimidine nucleotide biosynthesis in animals: genes, enzymes and regulation of UMP biosynthesis. Annu. Rev. Biochem. 49, 255-279.
2. Löffler, M. (1980) On the role of dihydroorotate dehydrogenase in growth cessation of Ehrlich ascites tumor cells cultured under oxygen deficiency. Eur. J. Biochem. 107, 207-215.
3. Amellem, O., Löffler, M. & Pettersen, E.O. (1994) Regulation of cell proliferation under extreme and moderate hypoxia: the role of pyrimidine (deoxy)nucleotides. Br. J. Cancer 70, 857-866.
4. Löffler, M., Becker, C., Wegerle, E. & Schuster, G. (1996) Catalaytic enzyme histochemistry and biochemical analysis of dihydroorotate dehydrogenase / oxidase and succinate dehydrogenase in mammalian tissues, cells and mitochondria. Histochem. Cell Biol. 105, 119-128.
5. Forman, H.J. & Kennedy, J. (1977) Purification of the primary dihydroorotate dehydrogenase (oxidase) from rat liver mitochondria. Prep. Biochem. 7, 394-401.
6. Hines, V. Keys, L.D. & Johnstone M. (1986) Purification and properties of the bovine liver mitochondrial dihydroorotate dehydrogenase. J. Biol. Chem. 261, 11386-11392.
7. Lakaschus, G. & Löffler, M. (1992) Differential susceptibility of dihydroorotate dehydrogenase / oxidase to brequinar sodium (NSC 368390) in vitro. Biochem. Pharmacol. 43, 1025-1030.
8. Williamson, R.A., Yea, C.M., Robson, P., Curnock, A., Suresh, G., Hambleton, A.B., Moss, D., Thomson, T.A., Spinella-Jaegle, S., Morand, P. Courtin O., Sautéts, C., Westwood, R., Hercend, T., Kuo, E.A. & Ruuth, E. ( 1995) Dihydroorotate dehydrogenase, a high affinity binding protein for A77 1726 and mediator of a range of biological effects of the immunomodulatory compound. J. Biol. Chem. 270, 22467-22472.
9. Lakaschus, G., Krüger, H., Heese, D. Löffler, M. (1991) Dihydroorotate dehydrogenase may be a source of toxic oxygen species. Adv. Exp. Med. Biol.309, 361-364.
10. Knecht, W., Bergjohann, U., Gonski, S., Kirschbaum, B. & Löffler, M. (1996) Functional expression of a fragment of human dihydroorotate dehydrogenase by means of the baculovirus expression vector system, and kinetic investigation of the purified recombinant enzyme.Eur. J. Biochem. 240, 292-301.
11. Copeland, R.A., Davis, J.P., Dowling, R.L. Lombardo, D., Murphy, K.B. & Patterson, T.A. (1995) Recombinant human dihydroorotate dehydrogenase: expression, purification, and characterization of a catalytically functional truncated enzyme. Arch. Biochem. Biophys. 323, 79-86.
12. Knecht, W., Altekruse, D., Rotgeri, A. Gonski, S. Löffler, M. (1997) Dihydroorotate dehydrogenase: isolation of the recombinant enzyme from mitochondria of insect cells. Prot: Expr. Purif. 10, 89-99.
13. Rotgeri, A. & Löffler, M. (1995) Molecular cloning and sequence analysis of rat liver dihydroorotate dehydrogenase. Adv. Exp. Med. Biol. 370, 693-698.
14. Cysk, R.L., Malinowski, N., Marquez, V., Zaharevitz, D., August. E.M. Moyer, J.D. (1995) Cyclopentenyl uracil: an effective inhibitor of uridine salvage in vivo. Biochem. Pharmacol. 49, 203-207.
15. Benett, L.L., Smithers, D., Rose, L.M., Adamson, D.J. & Thomas, H.J. (1979) Inhibition of synthesis of pyrimidine nucleotides by 2-hydroxy-3-(3,3-dichloroallyl)-1,4-naphtoquinone. Cancer Res. 39, 4868-4874.
16. Cramer, D.V. (1996) Brequinar Sodium. Transplant. Proced. 28, 960-963.
17. Greene, S., Watanabe, K., Braatz-Trulson, J. & Lou, L. (1995) Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem. Pharmacol. 50, 861-867.
18. Harder, A. & Haberkorn, A. (1989) Possible mode of action of toltrazuril: studies on two Eimeria species and mammalian and Ascaris suum enzymes. Parasitol. Res. 76, 8-12.
19. Ittarat, I., Asawamahasaka, A., Bartlett, M.S., Smith, J.W. & Meshnick, S.R. (1995) Effects of Atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate dehydrogenase. Antimicrob. Agents Chemother. 39, 325-328.
20. Bartlett, R.R., Dimitrijevic, M., Mattar, T., Zielinski, T., Germann T., Rüde, E., Thoenes, G.H., Küchle, C.C. A., Schorlemmer, H.U., Bremer, E., Finnegan, A. & Schleyerbach, R. (1991) Leflunomide (HWA 486), a novel immunomodulating compound for the treatment of autoimmune disorders and reactions to transplantation rejection. Agents and Actions 32, 10-21.
21. Schorlemmer, H.U., Bartlett, R.R. Kurrle, R. (1997) Analogues of Leflunomide's primary metabolite, the malononitrilamides, prevent the development of graft-versus-host disease.Transplant. Proc. 29, 1298-1301.
22. Löffler, M., Jockei, J. Schuster, G., & Becker, C. (1997) Dihydroorotate dehydrogenase links mitochondria in the biosynthesis of pyrimidines. Mol. Cell. Biochem. in press.
23. Nilson, K. & Sundstrom, P. (1976) Int. Nat. J. Cancer 17, 565-577.