Mechanistic study of amine oxidation catalysed by quinonoid cofactors

Abstract

A kinetic study was performed on the oxidative deamination of benzylamine (BzAm) catalysed by pyrroloquinoline quinone (PQQ), a tryptophan tryptophylquinone analogue [3-methyl-4-(3′-methylindol-2′-yl)indole-6,7-dione; TTQ_a], and a topa quinone analogue (6-hydroxydopa quinone; TPQ_a) using high-performance liquid chromatography under aerobic conditions and cyclic voltammetry under anaerobic conditions. The overall kinetics are second-order in the quinone and BzAm concentrations and independent of the electron acceptors used (dioxygen under aerobic conditions and electrode under anaerobic conditions). The second-order rate constants vs. pH profiles are explained in terms of the acid dissociation of BzAm and the quinones, yielding pH-independent second-order rate constants, which are in the order TTQ_a > PQQ ⪢ TPQ_a . Half-wave potentials of steady-state catalytic voltammograms are more positive than the redox potentials of the free quinones, indicating that the BzAm-reduced quinones are not quinols but the corresponding aminophenols, which are oxidized to iminoquinones. Iminoquinone forms of PQQ and TTQ_a exhibit lower catalytic activity compared with the quinone forms. The reaction rate of TTQ_a slows down with the time, while those of PQQ and TPQ_a are practically independent of the reaction time within a 15 min period. The diminished rate of TTQ_a is reasonably ascribed to slow hydrolysis of imino-TTQ_a to TTQ_a. Generation of the iminosemiquinone radical during the catalytic reactions is evidenced by EPR spectroscopic measurements. The significance of radical generation is discussed in the light of autoxidation of the aminophenols. All these results are interpreted well by a transamination mechanism. In addition, an asymmetric ortho-quinone structure is proposed to be important in catalytic amine oxidation activity, and the relatively low catalytic activity of free TPQ_a is ascribed to the contribution of a para-quinone-type electronic structure. On the basis of these results, a role for Cu^II is proposed as a transient intramolecular electron acceptor in copper amine oxidases to enhance the reactivity toward dioxygen through the generation of the imino-TPQ semiquinone and as a weak ligand in TPQ-containing amine oxidases making the TPQ cofactor bear an ortho-quinone-type electronic structure.

References

1. S. A. Salisbury, H. A. Forrest, W. B. T. Cruse and O. Kennard, Nature, 1979, 280, 843; J. Westerling, J. Frank and J. A. Duine, Biochem. Biophys. Res. Commun., 1979, 87, 719.
2. S. M. Janes, D. Mu, D. Wemmer, A. J. Smith, S. Kaur, A. L. Burlingame and J. P. Klinman, Science, 1990, 248, 981.
3. W. S. McIntire, D. E. Wemmer, A. Y. Christoserdov and M. E. Lidstrom, Science, 1991, 252, 817.
4. S. X. Wang, M. Mure, K. F. Medzihradszky, A. L. Burlingame, D. E. Brown, D. M. Dooley, A. J. Smith, H. M. Kagan and J. P. Klinman, Science, 1996, 273, 1078.
5. For a review see: Principles and Applications of Quinoproteins, ed. V. L. Davidson, Marcel Dekker, New York, 1993.
6. For reviews see: Y. Ohshiro and S. Itoh, Bioorg. Chem., 1989, 19, 169; Y. Ohshiro and S. Itoh, in ref. 4, p. 309.
7. (a) T. S. Eckert and T. C. Bruice, J. Am. Chem. Soc., 1983, 105, 4431; (b) P. R. Sleath, J. B. Noar, G. A. Eberlein and T. C. Bruice, J. Am. Chem. Soc., 1985, 107, 3328; (c) E. J. Rodriguez and T. C. Bruice, J. Am. Chem. Soc., 1989, 111, 7947.
8. (a) M. Mure and J. P. Klinman, J. Am. Chem. Soc., 1993, 115, 7117; (b) M. Mure and J. P. Klinman, J. Am. Chem. Soc., 1995, 117, 8698; (c) M. Mure and J. P. Klinman, J. Am. Chem. Soc., 1995, 117, 8718; (d) J. P. Klinman, Chem. Rev., 1996, 96, 2541.
9. (a) F. Wang, J.-Y. Bae, A. R. Jacobson, Y. Lee and L. M. Sayre, J. Org. Chem., 1994, 59, 2409; (b) Y. Lee and L. M. Sayre, J. Am. Chem. Soc., 1995, 117, 3096.
10. (a) S. Itoh, M. Ogino, M. Komatsu and Y. Ohshiro, J. Am. Chem. Soc., 1992, 114, 7294; (b) S. Itoh, M. Ogino, S. Haranou, T. Terasaka, T. Ando, M. Komatsu, Y. Ohshiro, S. Fukuzumi, K. Kano, K. Takagi and T. Ikeda, J. Am. Chem. Soc., 1995, 117, 1485.
11. (a) J. Z. Pedersen, S. El-Sherbini, A. Finazzi-Agrň and G. Rotilio, Biochemistry, 1992, 31, 8; (b) N. Nakamura, T. Kohzuma, H. Kuma and S. Suzuki, J. Am. Chem. Soc., 1992, 114, 6550; (c) M. A. Shah, P. R. Bergethon, A. M. Boak, P. M. Gallop and H. M. Kagan, Biochem. Biophys. Acta, 1992, 1159, 311; (d) K. Kano, T. Mori, B. Uno, M. Goto and T. Ikeda, Biochem. Biophys. Acta, 1993, 1157, 324; (e) M. Bosa, G. O. Morpurgo and L. Morpurgo, Biochemistry, 1994, 33, 4425.
12. V. L. Davidson, L. H. Jones and M. E. Graichen, Biochemistry, 1992, 31, 3385.
13. C. Hartmann and J. P. Klinman, J. Biol. Chem., 1987, 262, 962; C. Hartmann, P. Brzovic and J. P. Klinman, Biochemistry, 1993, 32, 2234.
14. R. Medda, A. Padiglia, J. Z. Pedersen, G. Rotilio, A. Finazzi-Agrň and G. Floris, Biochemistry, 1995, 34, 16 375.
15. G. R. Bishop, H. B. Brooks and V. L. Davidson, Biochemistry, 1996, 35, 8948.
16. (a) D. M. Dooley, M. A. McGuirl, D. E. Brown, P. N. Turowski, W. McIntire and P. F. Knowles, Nature, 1991, 349, 262; (b) P. N. Turowski, M. A. McGuirl and D. M. Dooley, J. Biol. Chem., 1993, 268, 17 680; (c) D. M. Dooley, W. S. McIntire, M. A. McGuirl, C. E. Cote and J. L. Bates, J. Am. Chem. Soc., 1990, 112, 2782.
17. J. McCracken, J. Peisach, C. E. Cote, M. A. McGuirl and D. M. Dooley, J. Am. Chem. Soc., 1992, 114, 3715.
18. A. Finazzi-Agrň, A. Rinaldi, G. Floris and G. Rotilio, FEBS Lett., 1984, 176, 378.
19. (a) V. L. Davidson, Methods Enzymol., 1990, 188, 241; (b) K. Warncke, H. B. Brooks, G. T. Babcock, V. L. Davidson and J. McCracken, J. Am. Chem. Soc., 1993, 115, 6464.
20. A. C. F. Gorren, S. de Vries and J. A. Duine, Biochemistry, 1995, 34, 9748.
21. D. M. Dooley, W. S. McIntire, M. A. McGuirl, C. E. Coté and J. L. Bates, J. Am. Chem. Soc., 1990, 112, 2782.
22. K. P. S. Yadav and P. F. Knowles, Eur. J. Biochem., 1981, 114, 139.
23. K. Kano, K. Mori, B. Uno, T. Kubota, T. Ikeda and M. Senda, Bioelectrochem. Bioenerg., 1990, 23, 227.
24. S. Itoh, Y. Kitamura, Y. Ohshiro and T. Agawa, Bull. Chem. Soc. Jpn., 1986, 59, 1907.
25. Lange's Handbook of Chemistry, ed. J. A. Dean, 12th edn., McGraw-Hill, New York, 1979, ch. 5, p. 21.
26. S. Itoh, Y. Fukui, S. Haranou, M. Ogino, M. Komatsu and Y. Ohshiro, J. Org. Chem., 1992, 57, 4452.
27. A. J. Bard and L. R. Faulkner, in Electrochemical Methods: Fundamentals and Applications, Wiley, New York, 1980, p. 457.
28. Ref. 27, p. 143.
29. H. Tatsumi, K. Kano and T. Ikeda, Presented at the Annual Meeting of The Agricultural Chemistry Society of Japan held in Kyoto, March 30–April 2, 1996, Abstr., p. 69.
30. J. M. Savéant and E. Vianello, Electrochim. Acta, 1965, 10, 905; Y. Ogino, K. Takagi, K. Kano and T. Ikeda, J. Electroanal. Chem., 1995, 396, 517.
31. K. Kano, K. Mori, B. Uno and M. Goto, J. Electroanal. Chem., 1990, 293, 177.
32. Ref. 25, ch. 5, p. 42.
33. V. L. Davidson, Biochem. J., 1989, 261, 107.
34. Theoretically, eqn. (2) should be applied to the condition where the electroactive species (TTQ_a in this case) in the bulk phase is in the reduced form for the oxidative catalysis. When the oxidized TTQ_a remains somewhat in the bulk phase and is reduced slowly by BzAm during the voltammetric measurements, the oxidation current becomes slightly larger than expected by eqn. (2) due to the contribution of the substrate-reduced TTQ_a generated in the bulk.
35. W. S. McIntire, J. Biol. Chem., 1987, 262, 11 012.
36. V. L. Davidson and L. H. Jones, Biochim. Biophys. Acta, 1992, 1121, 104.
37. E. J. Corey and K. Achiwa, J. Am. Chem. Soc., 1969, 91, 1429; R. F. X. Klein, L. M. Bargas and V. Horak, J. Org. Chem., 1988, 53, 5994.
38. For a review see: G. Dryhurst, K. M. Kadish, F. Sheller and R. Renneberg, in Biological Electrochemistry, Academic Press, New York, 1982, vol. 1, ch. 2, pp. 116–179.
39. K. Kano, T. Konse, B. Uno and T. Kubota, in Redox Chemistry and Interfacial Behavior of Biological Molecules, eds. G. Dryhurst and K. Niki, Plenum, New York, 1988, p. 267.
40. C. Kemal, T. W. Chan and T. C. Bruice, J. Am. Chem. Soc., 1977, 99, 7272.
41. W. C. Kenny and W. McIntire, Biochemistry, 1983, 22, 3858.
42. M. Husain, V. L. Davidson, K. A. Gray and D. B. Knaff, Biochemistry, 1987, 26, 4139.
43. D. M. Dooley, M. A. McGuirl, C. E. Cote, P. F. Knowles, I. Singh, M. Spiller, R. D. III Brown and S. H. Knoening, J. Am. Chem. Soc., 1991, 113, 154; M. A. McGuirl, D. E. Brown, C. D. McCahon, P. N. Turawski and D. M. Dooley, J. Inorg. Biochem., 1991, 43, 186.