The fourth molybdenum containing enzyme mARC: Cloning and involvement in the activation of N-hydroxylated prodrugs

Journal of Medicinal Chemistry

Volumn 51, Issue 24, 2008, Pages 8173-8177

  Gruenewald, Sanja ^a   Wahl, Bettina ^b   Bittner, Florian ^b   Hungeling, Helen ^a   Kanzow, Stephanie ^a   Kotthaus, Joscha ^a   Schwering, Ulrike ^a   Mendel, Ralf R ^b   Clement, Bernd ^a  

^a UNIVERSITY OF KIEL   (Germany)

^b TECHNICAL UNIVERSITY OF BRAUNSCHWEIG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

BENZAMIDOXIME; CYTOCHROME B5; CYTOCHROME B5 REDUCTASE; DEBRISOQUINE; DIMINAZENE; GUANOXABENZ; MELAGATRAN; MOLYBDENUM; N HYDROXYDEBRISOQUINE; N HYDROXYMELAGATRAN; PENTAMIDINE; PRODRUG; PROTEIN; PROTEIN MARC1; RECOMBINANT ENZYME; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; DRUG BIOAVAILABILITY; DRUG STRUCTURE; HUMAN; NONHUMAN; NUCLEOTIDE SEQUENCE; PREDICTION; PROTEIN EXPRESSION; REDUCTION;

ANIMALS; BENZAMIDINES; CATTLE; CELL LINE; CHEMISTRY, PHARMACEUTICAL; CLONING, MOLECULAR; CYTOCHROME-B(5) REDUCTASE; DRUG DESIGN; HUMANS; LIGANDS; MODELS, CHEMICAL; MOLYBDENUM; OXIDOREDUCTASES; PRODRUGS; RECOMBINANT PROTEINS; TEMPERATURE;

EID: 58149084441     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm8010417     Document Type: Article

References (34)

1. Clement, B. Reduction of N-hydroxylated compounds: amidoximes (N-hydroxyamidines) as pro-drugs of amidines. Drug Metab. Rev. 2002, 34, 565-579.
2. Gustafsson, D.; Nystrom, J.; Carlsson, S.; Bredberg, U.; Eriksson, U.; Gyzander, E.; Elg, M.; Antonsson, T.; Hoffmann, K.; Ungell, A.; Sorensen, H.; Nagard, S.; Abrahamsson, A.; Bylund, R. The direct thrombin inhibitor melagatran and its oral prodrug H 376/95: intestinal absorption properties, biochemical and pharmacodynamic effects. Thromb. Res. 2001, 101, 171-181.
3. Clement, B.; Lopian, K. Characterization of in vitro biotransformation of new, orally active, direct thrombin inhibitor ximelagatran, an amidoxime and ester prodrug. Drug Metab. Dispos. 2003, 31, 645-651.
4. Peterlin-Masic, L.; Cesar, J.; Zega, A. Metabolism-directed optimisation of antithrombotics: the prodrug principle. Curr. Pharm. Des. 2006, 12, 73-91.
5. Clement, B.; Raether, W. Amidoximes of pentamidine: synthesis, trypanocidal and leishmanicidal activity. Arzneimittelforschung 1985, 35, 1009-1014.
6. Bray, P. G.; Barrett, M. P.; Ward, S. A.; de Koning, H. P. Pentamidine uptake and resistance in pathogenic protozoa: past, present and future. Trends Parasitol. 2003, 19, 232-239.
7. Clement, B.; Demesmaeker, M.; Linne, S. Microsomal catalyzed N-hydroxylation of guanabenz and reduction of the N-hydroxylated metabolite: characterization of the two reactions and genotoxic potential of guanoxabenz. Chem. Res. Toxicol. 1996, 9, 682-688.
8. Kadlubar, F. F.; McKee, E. M.; Ziegler, D. M. Reduced pyridine nucleotide-dependent N-hydroxy amine oxidase and reductase activities of hepatic microsomes. Arch. Biochem. Biophys. 1973, 156, 46-57.
9. Kadlubar, F. F.; Ziegler, D. M. Properties of a NADH-dependent N-hydroxy amine reductase isolated from pig liver microsomes. Arch. Biochem. Biophys. 1974, 162, 83-92.
10. Bernheim, M. L.; Hochstein, P. Reduction of hydroxylamine by rat liver mitochondria. Arch. Biochem. Biophys. 1968, 124, 436-442.
11. Bernheim, M. L. The hydroxylamine reductase of mitochondria. Arch. Biochem. Biophys. 1969, 134, 408-413.
12. Bernheim, M. L. The reduction of hydroxylamine and some aryl hydroxamates by liver mitochondria from mammals and birds. Enzymologia 1972, 43, 167-176.
13. Clement, B.; Lomb, R.; Möller, W. Isolation and characterization of the protein components of the liver microsomal O2-insensitive NADH-benzamidoxime reductase. J. Biol. Chem. 1997, 272, 19615-19620.
14. Havemeyer, A.; Bittner, F.; Wollers, S.; Mendel, R.; Kunze, T.; Clement, B. Identification of the missing component in the mitochondrial benzamidoxime prodrug-converting system as a novel molybdenum enzyme. J. Biol. Chem. 2006, 281, 34796-34802.
15. Nason, A.; Lee, K. Y.; Pan, S. S.; Ketchum, P. A.; Lamberti, A.; DeVries, J. In vitro formation of assimilatory reduced nicotinamide adenine dinucleotide phosphate: nitrate reductase from a Neurospora mutant and a component of molybdenum enzymes. Proc. Natl. Acad. Sci. U.S.A 1971, 68, 3242-3246.
16. Andersson, S.; Hofmann, Y.; Nordling, A.; Li, X. Q.; Nivelius, S.; Andersson, T. B.; Ingelman-Sundberg, M.; Johansson, I. Characterization and partial purification of the rat and human enzyme systems active in the reduction of N-hydroxymelagatran and benzamidoxime. Drug Metab. Dispos. 2005, 33, 570-578.
17. Kurian, J. R.; Bajad, S. U.; Miller, J. L.; Chin, N. A.; Trepanier, L. A. NADH cytochrome b5 reductase and cytochrome b5 catalyze the microsomal reduction of xenobiotic hydroxylamines and amidoximes in humans. J. Pharmacol. Exp. Ther. 2004, 311, 1171-1178.
18. Kurian, J. R.; Chin, N. A.; Longlais, B. J.; Hayes, K. L.; Trepanier, L. A. Reductive detoxification of arylhydroxylamine carcinogens by human NADH cytochrome b5 reductase and cytochrome b5. Chem. Res. Toxicol. 2006, 19, 1366-1373.
19. Saulter, J. Y.; Kurian, J. R.; Trepanier, L. A.; Tidwell, R. R.; Bridges, A. S.; Boykin, D. W.; Stephens, C. E.; Anbazhagan, M.; Hall, J. E. Unusual dehydroxylation of antimicrobial amidoxime prodrugs by cytochrome b5 and NADH cytochrome b5 reductase. Drug Metab. Dispos. 2005, 33, 1886-1893.
20. Clement, B.; Behrens, D.; Amschler, J.; Matschke, K.; Wolf, S.; Havemeyer, A. Reduction of sulfamethoxazole and dapsone hydroxylamines by a microsomal enzyme system purified from pig liver and pig and human liver microsomes. Life Sci. 2005, 77, 205-219.
21. Clement, B.; Mau, S.; Deters, S.; Havemeyer, A. Hepatic, extrahepatic, microsomal, and mitochondrial activation of the N-hydroxylated prodrugs benzamidoxime, guanoxabenz, and Ro 48-3656 ([[1-[(2s)-2-[[4- [(hydroxyamino)iminomethyl]benzoyl]amino]-1-oxopropyl]-4-piperid inyl]oxy]-acetic acid). Drug Metab. Dispos. 2005, 33, 1740-1747.
22. Torres, R. A.; Korzekwa, K. R.; McMasters, D. R.; Fandozzi, C. M.; Jones, J. P. Use of density functional calculations to predict the regioselectivity of drugs and molecules metabolized by aldehyde oxidase. J. Med. Chem. 2007, 50, 4642-4647.
23. Sergeev, G. V.; Gilep, A. A.; Estabrook, R. W.; Usanov, S. A. Expression of outer mitochondrial membrane cytochrome b5 in Escherichia coli purification of the recombinant protein and studies of its interaction with electron-transfer partners. Biochemistry (Moscow) 2006, 71, 790-799.
24. Shirabe, K.; Landi, M. T.; Takeshita, M.; Uziel, G.; Fedrizzi, E.; Borgese, N. A novel point mutation in a 3′ splice site of the NADH-cytochrome b5 reductase gene results in immunologically undetectable enzyme and impaired NADH-dependent ascorbate regeneration in cultured fibroblasts of a patient with type II hereditary methemoglobinemia. Am. J. Hum. Genet. 1995, 57, 302-310.
25. Wittke, B.; Mackie, I. J.; Machin, S. J.; Timm, U.; Zell, M.; Goggin, T. Pharmacokinetics and pharmacodynamics of Ro 44-3888 after single ascending oral doses of sibrafiban, an oral platelet aggregation inhibitor, in healthy male volunteers. Br. J. Clin. Pharmacol. 1999, 47, 521-530.
26. Lanteri, C. A.; Trumpower, B. L.; Tidwell, R. R.; Meshnick, S. R. DB75, a novel trypanocidal agent, disrupts mitochondrial function in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 2004, 48, 3968-3974.
27. Stuehr, D. J.; Kwon, N. S.; Nathan, C. F.; Griffith, O. W.; Feldman, P. L.; Wiseman, J. N-omega-Hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine. J. Biol. Chem. 1991, 266, 6259-6263.
28. Krüger, P. Ueber Abkömmlinge des Benzenylamidoxims. Ber. Dtsch. Chem. Ges. 1885, 18, 1055-1060.
29. Clement, B.; Bürenheide, A.; Rieckert, W.; Schwarz, J. Diacetyldiamidoximeester of pentamidine, a prodrug for treatment of protozoal diseases: synthesis, in vitro and in vivo biotransformation. ChemMedChem 2006, 1, 1260-1267.
30. Clement, B.; Immel, M.; Raether, W. Metabolic N-hydroxylation of diminazene in vitro. Arzneimittelforschung 1992, 42, 1497-1504.
31. Bailey, D. M.; DeGrazia, C. G. Hydroxyguanidines. A new class of antihypertensive agents. J. Med. Chem. 1973, 16, 151-156.
32. Palmer, T.; Santini, C. L.; IobbiNivol, C.; Eaves, D. J.; Boxer, D. H.; Giordano, G. Involvement of the narJ and mob gene products in distinct steps in the biosynthesis of the molybdoenzyme nitrate reductase in Escherichia coli. Mol. Microbiol. 1996, 20, 875-884.
33. Johnson, J. L.; Rajagopalan, K. V. Structural and metabolic relationship between the molybdenum cofactor and urothione. Proc. Natl. Acad. Sci. U.S.A 1982, 79, 6856-6860.
34. Schwarz, G.; Boxer, D. H.; Mendel, R. R. Molybdenum cofactor biosynthesis. The plant protein Cnx1 binds molybdopterin with high affinity. J. Biol. Chem. 1997, 272, 26811-26814.