Spiropentylacetyl-CoA, a mechanism-based inactivator of acyl-CoA dehydrogenases

Journal of the American Chemical Society

Volumn 120, Issue 9, 1998, Pages 2008-2017

  Li, Ding ^a,b   Zhou, Hui Qiang ^a,c   Dakoji, Srikanth ^a   Shin, Injae ^a,d   Oh, Eugene ^a,e   Liu, Hung Wen ^a  

^a University of Minnesota ^*  (United States)

^b TEXAS A AND M UNIVERSITY   (United States)

^c UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^d Yonsei University   (South Korea)

^e Samsung Advanced Institute of Technology (SAIT)   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DEHYDROGENASE; ENZYME INHIBITOR; FLAVINE ADENINE NUCLEOTIDE; HYPOGLYCINE A; SPIROPENTYLACETYL COENZYME A; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; ELECTRON TRANSPORT; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INACTIVATION; ENZYME MECHANISM; FATTY ACID METABOLISM; NONHUMAN;

EID: 2642710916     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9737634     Document Type: Article

References (76)

1. (a) Thorpe, C.; Matthews, R. G.; Williams, C. H. Biochemistry 1979, 18, 331.
2. (b) Ghisla, S.; Thorpe, C.; Massey, V. Biochemistry 1984, 23, 3154.
3. (c) Pohl, B.; Raichle, T.; Ghisla, S. Eur. J. Biochem. 1986, 160, 109.
4. (d) Ghisla, S. In Flavins and Flavoproteins; Bray, R. C., Engel, P. C., Mayhew, S. G., Eds.; Walter de Gruyter & Co.: Berlin, 1984; p 385 and references cited therein.
5. (a) Beinert, H. Enzymes, 2nd ed.; 1963, 7, 447.
6. (b) Engel, P. C. In Chemistry and Bio-chemistry of Flavoenzymes; Müller, F., Ed.; CRC Press: New York, 1991; p 597.
7. (c) Schulz, H. In Fatty Acid Oxidation: Clinical, Biochemical, and Molecular Aspects; Tanaka, K., Coates, P. M., Eds.; Alan R. Liss: New York, 1990; p 23.
8. (d) Ikeda, Y.; Okamura-Ikeda, K.; Tanaka, K. J. Biol. Chem. 1985, 260, 1311.
9. (e) Izai, K.; Uchida, Y.; Ori, T.; Yamamoto, S.; Hashimoto, T. J. Biol. Chem. 1992, 267, 1027.
10. (a) Ghisla, S.; Engst, S.; Moll, M.; Bross, P.; Strauss, A.; Kim, J. J. P. In New Developments in Fatty Acid Oxidation; Coates, P. M., Tanaka, K., Eds.; Wiley-Liss: New York, 1992; p 127.
11. (b) Kim, J. J. P. In Flavins and Flavoproteins; Curti, B., Ronchi, S., Zanetti, G., Eds.; de Gruyter: New York, 1991; p 291.
12. (c) Kim, J. J. P.; Wang, M.; Djordjevic, S.; Paschke, R. In New Developments in Fatty Acid Oxidation; Coates, P. M., Tanaka, K., Eds.; Wiley-Liss: New York, 1992; p 111.
13. (d) Kim, J. P.; Wang, M.; Paschke, R. Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 7523.
14. (e) Bross, P.; Engst, S.; Strauss, A. W.; Kelley, D. P.; Rasched, I.; Ghisla, S. J. Biol. Chem. 1990, 265, 7116.
15. (f) Becker, D. F.; Fuchs, J. A.; Banfield, D. K.; Walter, F. D.; MacGillivray, R. T. A.; Stankovich, M. T. Biochemistry 1993, 32, 10736.
16. (a) Biellmann, J. F.; Hirth, C. G. FEBS Lett. 1970, 9, 55, 335.
17. (b) Bucklers, L.; Umani-Ronchi, A. S.; Retéy, J.; Arigoni, D. Experientia 1970, 26, 931.
18. (c) Dommes, V.; Kunau, W.-H. J. Biol. Chem. 1984, 259, 1789.
19. (d) Ikeda, Y.; Tanaka, K. In Fatty Acid Oxidation: Clinical, Biochemical, and Molecular Aspects; Tanaka, K., Coates, P. M., Eds.; Alan R. Liss: New York, 1990; p 37.
20. (a) Lenn, N. D.; Shih, Y.; Stankovich, M. T.; Liu, H.-w. J. Am. Chem. Soc. 1989, 111, 3065.
21. (b) Lai, M.-t.; Liu, H.-w. J. Am. Chem. Soc. 1990, 112, 4034.
22. (c) Baldwin, J. E.; Ostrander, R. L.; Simon, C. D.; Widdison, W. C. J. Am. Chem. Soc. 1990, 112, 2021.
23. (d) Lai, M.-t.; Liu, L.-d.; Liu, H.-w. J. Am. Chem. Soc. 1991, 113, 7388.
24. (e) Lai, M.-t.; Liu, H.-w. J. Am. Chem. Soc. 1992, 114, 3160.
25. (f) Baldwin, J. E.; Widdison, W. C. J. Am. Chem. Soc. 1992, 114, 2245.
26. (g) Lai, M.-t.; Li, D.; Oh, E.; Liu, H.-w. J. Am. Chem. Soc. 1993, 115, 1619.
27. Cummings, J. G.; Thorpe, C. Biochemistry 1994, 33, 788.
28. (a) Fendrich, G.; Abeles, R. H. Biochemistry 1982, 21, 6685.
29. (b) Powell, P. J.; Thorpe, C. Biochemistry 1988, 27, 8022.
30. (c) Freund, K.; Mizzer, J. P.; Dick, W.; Thorpe, C. Biochemistry 1985, 25, 5996.
31. (d) Lundberg, N. N.; Thorpe, C. Arch. Biochem. Biophys. 1993, 454.
32. (e) Frerman, F. E.; Miziorko, H. M.; Beckmann, J. D. J. Biol. Chem. 1980, 255, 11192.
33. (f) Gomes, B.; Fendrich, G.; Abeles, R. H. Biochemistry 1981, 20, 1481.
34. (a) Osmundsen, H.; Sherratt, H. S. A. FEBS Lett. 1975, 55, 81.
35. (b) Kean, E. A. Biochem. Biophys. Acta 1976, 422, 81.
36. (c) Abeles, R. H. In Enzyme Activated Irreversible Inhibitors; Seiler, N., Jung, M. J., Koch-Weser, J., Eds.; Elsevier-North-Holland: Amsterdam, 1978; p 1.
37. (d) Ghisla, S.; Wenz, A.; Thorpe, C. In Enzyme Inhibitors; Brodbeck, U., Ed.; Verlag Chim: Weinheim, Germany, 1980; p 43.
38. (e) Wenz, A.; Thorpe, C.; Ghisla, S. J. Biol. Chem. 1981, 256, 9809.
39. (f) Ghisla, S.; Melde, K.; Zeller, H. D.; Boschert, W. In Fatty Acid Oxidation; Clinical, Biochemical, and Molecular Aspects; Tanaka, K., Coates, P. M., Eds.; Alan R. Liss, Inc.: New York, 1990; p 185.
40. Tserng, K. Y.; Jin, S.-J.; Hoppel, C. L. Biochemistry 1991, 30, 10755.
41. Ullman, E. F.; Fanshawe, W. J. J. Am. Chem. Soc. 1961, 83, 2379.
42. (a) Rojas, C.; Schmidt, J.; Lee, M.-Y.; Gustafson, W. G.; McFarland, J. T. Biochemistry 1985, 24, 2947.
43. (b) Johnson, J. K.; Srivastava, D. K. Biochemistry 1993, 32, 8004.
44. Thorpe, C. Methods Enzymol. 1981, 71, 366.
45. Baldwin, J. E.; Parker, D. W. J. Org. Chem. 1987, 52, 1475.
46. Zefirov, N. S.; Kozhushkov, S. I.; Ugrak, B. I.; Lukin, K. A.; Kokoreva, O. V.; Yufit, D. S.; Struchkov, Y. T.; Zoellner, S.; Boese, R.; de Meijere, A. J. Org. Chem. 1992, 57, 701.
47. Dakoji, S.; Shin, I.; Becker, D. F.; Stankovich, M. T.; Liu, H.-w. J. Am. Chem. Soc. 1996, 118, 10971.
48. Lehman, T. C.; Hale, D. E.; Bhala, A.; Thorpe, C. Anal. Biochem. 1990, 186, 280.
49. (a) Kabat, M. M.; Wicha, J. Tetrahedron Lett. 1991, 32, 531.
50. (b) Lai, M.-t.; Oh, E.; Shih, Y.; Liu, H.-w. J. Org. Chem. 1992, 57, 2471.
51. (c) Lai, M.-t.; Oh, E.; Liu, H.-w. Bioorg. Med. Chem. Lett. 1992, 2, 1423.
52. I for the inactivation of MCAD by 19 or 20 based on a similar approach shown in Figure 3 proved to be problematic. The inactivation follows first-order kinetics only at high inhibitor concentration but deviates from the first-order kinetics at low inhibitor concentration. The amount of inhibitor (260 mM) used in the incubations shown in Figure 4 was at the saturation conditions.
53. Russo, J. M.; Price, W. A. J. Org. Chem. 1993, 58, 3589.
54. Benson, S. W.; Cruickshank, F. R.; Golden, D. M.; Hauger, G. R.; O'Neal, H. E.; Rodgers, A. S.; Shaw, R.; Walsh, R. Chem. Rev. 1969, 69, 279.
55. (a) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317.
56. (b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 347.
57. (c) Newcomb, M. Tetrahedron 1993, 49, 1151.
58. (a) Newcomb, M.; Manek, M. B.; Glenn, A. G. J. Am. Chem. Soc. 1991, 113, 949.
59. (b) Bowry, V. W.; Lusztyk, J.; Ingold, K. U. J. Am. Chem. Soc. 1991, 113, 5687.
60. (c) Eaton, P. E.; Yip, Y. C. J. Am. Chem. Soc. 1991, 113, 7692.
61. (d) Choi, S.-Y.; Eaton, P. E.; Newcomb, M.; Yip, Y. C. J. Am. Chem. Soc. 1992, 114, 6326.
62. (a) Castellino, A. G.; Bruice, T. C. J. Am. Chem. Soc. 1988, 110, 7512.
63. (b) Newcomb, M.; Manek, M. B. J. Am. Chem. Soc. 1990, 112, 9662.
64. (c) Newcomb, M.; Johnson, C. C.; Manek, M. B.; Varick, T. R. J. Am. Chem. Soc. 1992, 114, 10915.
65. Horner, J. H.; Johnson, C. C.; Lai, M.-t.; Liu, H.-w.; Martin-Esker, A. A.; Newcomb, M.; Oh, E. Bioorg. Med. Chem. Lett. 1994, 4, 2693.
66. 20 It should be noted that the apparently greater ring strain associated with the spiropentyl system is misleading since it contains one more cyclopropyl ring than the methylenecyclopropane case. Interestingly, recent calculations showed that the major source of the "strain" resulting from the introduction of a trigonal center into cyclopropane is not the increase in angle strain but the loss of a very strong cyclopropane C-H bond (Johnson, W. T. G.; Borden, W. T. J. Am. Chem. Soc. 1997, 119, 5930).
67. Newcomb, M.; Horner, J. H.; Emanuel, C. J. J. Am. Chem. Soc. 1997, 119, 7147.
68. Cyclopropylcarbinyl radicals (such as 34) readily undergo β-scission because the SOMO can assume an eclipsed conformation with respect to a β,γ bond. On the contrary, cyclopropyl radicals (such as 35) cannot attain such a conformation without the development of great strain, and therefore, β-scission is hampered due to a much higher activation energy (Kennedy, A. J.; Walton, J. C.; Ingold, K. U. J. Chem. Soc., Perkin Trans. 2 1982, 751).
69. (a) Olson, S. T.; Massey, V.; Ghisla, S.; Whitfield, C. D. Biochemistry 1979, 18, 4724.
70. (b) Ghisla, S.; Olson, S. T.; Massey, V.; Lhoste, J. M. Biochemistry 1979, 18, 4733.
71. (c) Ghisla, S.; Ogata, H.; Massey, V.; Schonbrunn, A.; Abeles, R. H.; Walsh, C. T. Biochemistry 1976, 15, 1791.
72. (d) Schonbrunn, A.; Abeles, R. H.; Walsh, C. T.; Ghisla, S.; Ogata, H.; Massey, V. Biochemistry 1976, 15, 1798.
73. (e) Zeller, H. D.; Ghisla, S. In Flavins and Flavoproteins; Edmondson, D. E., McCormick, D. B., Eds.; Walter de Gruyter: Berlin, 1987; p 161.
74. The structures listed in Scheme 7 for the inhibitor-enzyme adducts are by no means a complete set of all possible variations. For example, a fully oxidized C-6-substituted flavin has also been proposed as the structure of a minor component isolated from the incubation of MCPA-CoA (5) with MCAD (Zeller, H. D.; Ghisla, S. In Flavins and Flavoproteins; Edmondson, D. E., McCormick, D. B., Eds.; Walter de Gruyter: Berlin, 1987; p 161).
75. Ab initio calculations were carried out to compute the energies of primary cyclopropylcarbinyl and tertiary cyclopropyl radicals using an unrestricted Hartree-Fock level of theory with 6-31G* basis set (UHF/6-3/G*). The results suggested that the energy difference is about 5 kcal/mol, favoring the primary cyclopropylcarbinyl radical. These energy differences reflect the bond dissociation energies (BDEs) of primary alkyl C-H versus the tertiary cyclopropyl C-H bonds (Borden, W. T. Personal communication).
76. Shin, I.; Li, D.; Becker, D. F.; Stankovich, M. T.; Liu, H.-w. J. Am. Chem. Soc. 1994, 116, 8843.