Dihydroorotase catalyzes the ring opening of the hydrolysis intermediates of the cardioprotective drug dexrazoxane (ICRF-187)

Drug Metabolism and Disposition

Volumn 30, Issue 12, 2002, Pages 1431-1435

  Schroeder, Patricia E ^a   Davidson, Jeffrey N ^b   Hasinoff, Brian B ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

^b UNIVERSITY OF KENTUCKY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2 PROPANEDIAMINE N,N' DIACETAMIDE N,N' DIACETIC ACID; ANTINEOPLASTIC AGENT; DIHYDROOROTASE; DIHYDROPYRIMIDINASE; DOXORUBICIN; FUROSEMIDE; IRON; PROTECTIVE AGENT; RAZOXANE; SULFONAMIDE; CARDIOTONIC AGENT;

ARTICLE; CARDIOTOXICITY; CATALYSIS; DRUG MECHANISM; DRUG METABOLISM; ENZYME ACTIVE SITE; ENZYME KINETICS; HEART PROTECTION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYDROLYSIS; PRIORITY JOURNAL; SPECTROPHOTOMETRY; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; HAMSTER; METABOLISM;

STAPHYLOCOCCUS PHAGE 187;

ANIMALS; CARDIOTONIC AGENTS; CATALYSIS; CRICETINAE; DIHYDROOROTASE; HYDROLYSIS; MODELS, MOLECULAR; RAZOXANE;

EID: 1842866539     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.30.12.1431     Document Type: Article

References (35)

1. Burkert U and Allinger NL (1982) Molecular Mechanics. ACS Monograph 177. American Chemical Society, Washington, DC.
2. Buss JL and Hasinoff BB (1993) The one-ring open hydrolysis product intermediates of the cardioprotective agent ICRF-187 (dexrazoxane) displace iron from iron-anthracycline complexes. Agents Actions 40:86-95.
3. Carrey EA (1993) Phosphorylation, allosteric effectors and inter-domain contacts in CAD: Their role in regulation of early steps of pyrimidine biosynthesis. Biochem Soc Trans 21:191-195.
4. Christopherson RI and Jones ME (1980) The effects of pH and inhibitors upon the catalytic activity of the dihydroorotase of multienzymatic protein pyrl-3 from mouse Ehrlich ascites carcinoma. J Biol Chem 254:12506-12512.
5. Christopherson RI, Schmalzl KJ, Szabados E, Goodridge RJ, Harsanyi MC, Sant ME, Algar EM, Anderson JE, Armstrong A, Sharma SC, et al. (1989) Mercaptan and dicarboxylate inhibitors of hamster dihydroorotase. Biochemistry 28:463-470.
6. Davidson JN, Chen KC, Jamison RS, Musmanno LA, and Kern CB (1993) The evolutionary history of the first three enzymes in pyrimidine biosynthesis. Bioessays 15:157-164.
7. Davidson JN, Rumsby PC, and Tamaren J (1981) Organization of a multifunctional protein in pyrimidine biosynthesis. Analyses of active, tryptic fragments. J Biol Chem 256:5220-5225.
8. Dawson KM (1975) Studies on the stability and cellular distribution of dioxopiperazines in cultured BHK-21S cells. Biochem Pharmacol 24:2249-2253.
9. Evans DR, Bein K, Guy HI, Liu X, Molina JA, and Zimmermann BH (1993) CAD gene sequence and the domain structure of the mammalian multifunctional protein CAD. Biochem Soc Trans 21:186-191.
10. Halliwell B and Gutteridge JMC (1989) Free Radicals in Biology and Medicine. Clarendon, Oxford.
11. Hasinoff BB (1990) The hydrolysis-activation of the doxorubicin cardioprotective agent ICRF-187 ((+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane). Drug Metab Dispos 18:344-349.
12. Hasinoff BB (1993) Enzymatic ring-opening reactions of the chiral cardioprotective agent (+) (S)-ICRF-187 and its (-) (R)-enantiomer ICRF-186 by dihydropyrimidine amidohydrolase. Drug Metab Dispos 21:883-888.
13. Hasinoff BB (1994a) An HPLC and spectrophotometric study of the hydrolysis of ICRF-187 (dexrazoxane, (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane) and its one-ring opened intermediates. Int J Pharm 107:67-76.
14. Hasinoff BB (1994b) Pharmacodynamics of the hydrolysis-activation of the cardioprotective agent (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane. J Pharm Sci 83:64-67.
15. Hasinoff BB (1998) Chemistry of dexrazoxane and analogues. Semin Oncol 25 (Suppl 10):3-9.
16. Hasinoff BB and Aoyama RG (1999) Relative plasma levels of the cardioprotective drug dexrazoxane and its two active ring-opened metabolites in the rat. Drug Metab Dispos 27:265-268.
17. Hasinoff BB, Hellmann K, Herman EH, and Ferrans VJ (1998) Chemical, biological and clinical aspects of dexrazoxane and other bisdioxopiperazines. Curr Med Chem 5:1-28.
18. Hasinoff BB, Reinders FX, and Clark V (1991) The enzymatic hydrolysis-activation of the adriamycin cardioprotective agent (+)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane. Drug Metab Dispos 19:74-80.
19. Hasinoff BB, Schroeder PE, and Patel D (2002) Mechanism of the prevention of doxorabicin-induced damage to heart myocytes by dexrazoxane (ICRF-187). Proc Am Assoc Cancer Res 43:1093.
20. Hasinoff BB, Venkataram S, Singh M, and Kuschak TI (1994) Metabolism of the cardioprotective agents dexrazoxane (ICRF-187) and levrazoxane (ICRF-186) by the isolated hepatocyte. Xenobiotica 24:977-987.
21. Hochster H, Liebes L, Wadler S, Oratz R, Wernz JC, Meyers M, Green M, Blum RH, and Speyer JL (1992) Pharmacokinetics of the cardioprotector ADR-529 (ICRF-187) in escalating doses combined with fixed-dose doxorubicin. J Natl Cancer Inst 84:1725-1730.
22. Huang DT, Thomas MA, and Christopherson RI(1999) Divalent metal derivatives of the hamster dihydroorotase domain. Biochemistry 38:9964-9970.
23. Kelly RE, Mally MI, and Evans DR (1986) The dihydroorotase domain of the multifunctional protein CAD. Subunit structure, zinc content and kinetics. J Biol Chem 261:6073-6083.
24. Kennedy J (1974) Dihydroorotase from rat liver: Purification, properties and regulatory role in pyrimidine biosynthesis. Arch Biochem Biophys 160:358-365.
25. Malisza KL and Hasinoff BB (1995) Production of hydroxyl radical by iron(III)-anthraquinone complexes through self-reduction and through reductive activation by the xanthine oxidase/hypoxanthine system. Arch Biochem Biophys 321:51-60.
26. Meyers CE (1998) The role of iron in doxorubicin-induced cardiomyopathy. Semin Oncol 25 (Suppl 10):10-14.
27. Pradhan TK and Sander EG (1973) Noncompetitive inhibition by unsubstituted sulfonamides of dihydroorotase from Zymobacterium oroticum. Life Sci 13:1747-1752.
28. Qiu Y and Davidson JN (2000) Substitutions in the aspartate transcarbamoylase domain of hamster CAD disrupt oligomeric structure. Proc Natl Acad Sci USA 97:97-102.
29. Schroeder PE and Hasinoff BB (2001) The metabolism of the doxorubicin cardioprotective agent, dexrazoxane (ICRF-187), to its active metal ion binding form ADR-925. Proc Am Assoc Cancer Res 42:383.
30. Schroeder PE, Jensen PB, Sehested M, Hofland K, Langer SW, and Hasinoff BB (2002) Metabolism of dexrazoxane (ICRF-187) used as a rescue agent in cancer patients treated with high-dose etoposide. Proc Am Assoc Cancer Res 43:274.
31. Simmer JP, Kelly RE, Rinker AG Jr, Zimmermann BH, Scully JL, Kim H, and Evans DR (1990) Mammalian dihydroorotase: Nucleotide sequence, peptide sequences and evolution of the dihydroorotase domain of the multifunctional protein CAD. Proc Natl Acad Sci USA 87:174-178.
32. Smith LH and Baker FA (1959) Pyrimidine metabolism in man. I. The biosynthesis of orotic acid. J Clin Invest 38:798-809.
33. Straughn AB, Wood GC, Raghow G, and Meyer MC (1986) Bioavailability of seven furosemide tablets in man. Biopharm Drug Dispos 7:113-120.
34. Thoden JB, Phillips GN Jr, Neal TM, Raushel FM, and Holden HM (2001) Molecular structure of dihydroorotase: A paradigm for catalysis through the use of a binuclear metal center. Biochemistry 40:6989-6997.
35. Williams NK, Manthey MK, Hambley TW, O'Donoghue SI, Keegan M, Chapman BE, and Christopherson RI (1995) Catalysis by hamster dihydroorotase: Zinc binding, site-directed mutagenesis and interaction with inhibitors. Biochemistry 34:11344-11352.