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Abstract

The concept of inhibition of growth of cells by an organic compound having specific structural features which would cause it to bind to a cell surface or protein molecule was introduced by Ehrlich in the late nineteenth century. However the concept of the antimetabolite, i e inhibition of a biochemical reaction by a compound similar in structure to a metabolite because of competition for a site on an enzyme molecule, has developed during the past twenty years. It is noteworthy that this development closely parallels the development of use of isotopes in the study of biochemical problems. That the two areas have not grown in different directions is evident from a survey of articles in any recent biochemical journal. Many investigators have used a combination of radioactive isotopes and anti-metabolites to gain information about biochemical mechanisms. It is, perhaps, in this area that the use of isotopes in the study of antimetabolites has achieved its greatest importance. It is the purpose of this chapter to point out how these concepts have been brought to bear in gaining information about a number of specific metabolic reactions. The choice of reactions and examples is dictated by personal interest, but the principles involved would be the same for an entirely different group of examples.

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Bibliography

  1. Cohn, M.: Bact. Rev. 21, 140 (1957).

    PubMed  CAS  Google Scholar 

  2. Cohen, G. N., and J. Monod: Bact. Rev. 21, 169 (1957).

    PubMed  CAS  Google Scholar 

  3. Roblin, R. O., Jr., J. O. Lampen, J. P. English, Q. P. Cole and J. R. Vaughan: J. Amer. chem. Soc. 67, 290 (1945).

    CAS  Google Scholar 

  4. Kidder, G. W., and V. C. Dewey: J. biol. Chem. 179, 181 (1949).

    PubMed  CAS  Google Scholar 

  5. Bennett, L. L., Jr., H. E. Skipper and L. W. Law: Fed. Proc. 12, 300 (1953).

    Google Scholar 

  6. Henrich, M. R., V. C. Dewey, R. E. Parks Jr. and G. W. Kidder: J. biol. Chem. 197, 199 (1952).

    Google Scholar 

  7. Mitchell, J. H., H. E. Skipper and L. L. Bennett: Cancer Res. 10, 647 (1950).

    CAS  Google Scholar 

  8. Mandel, H. G., P. E. Carlo and P. K. Smith: Fed. Proc. 12, 242 (1953).

    Google Scholar 

  9. Mandel, H. G., P. E. Carlo and P. K. Smith: J. biol. Chem. 206, 181 (1954).

    PubMed  CAS  Google Scholar 

  10. Mathews, R. E. F.: Nature (Lond.) 171, 1065 (1953).

    CAS  Google Scholar 

  11. Mathews, R. E. F.: J. gen. Microbiol. 10, 521 (1954).

    CAS  Google Scholar 

  12. Lasnitzki, I., R. E. F. Mathews and J. D. Smith: Nature (Lond.) 173, 346 (1954).

    CAS  Google Scholar 

  13. Smith, J. D., and R. E. F. Mathews: Biochem. J. 66, 323 (1957).

    PubMed  CAS  Google Scholar 

  14. Mandel, H. G., and R. Markham: Biochem. J. 65, 25P (1957).

    Google Scholar 

  15. Mandel, H. G.: J. biol. Chem. 225, 137 (1957).

    PubMed  CAS  Google Scholar 

  16. Mathews, R. E. F., and J. D. Smith: Nature (Lond.) 177, 271 (1956).

    Google Scholar 

  17. Markham, R., and J. D. Smith: Biochem. J. 52, 558 (1952).

    PubMed  CAS  Google Scholar 

  18. Mandel, H. G., and R. Markham: Biochem. J. 69, 297 (1958).

    PubMed  CAS  Google Scholar 

  19. Mandel, H. G., G. I. Sugarman and R. A. Apter: J. biol. Chem. 225, 151 (1957).

    PubMed  CAS  Google Scholar 

  20. Creaser, E. H.: Nature (Lond.) 176, 556 (1955).

    CAS  Google Scholar 

  21. Creaser, E. H.: Biochem. J. 64, 539 (1956).

    PubMed  CAS  Google Scholar 

  22. Mandel, H. G.: Arch. Biochem. Biophys. 76, 230 (1958).

    PubMed  CAS  Google Scholar 

  23. Dutton, R. W., A. H. Dutton and M. Goerge: Nature (Lond.) 182, 1377 (1958).

    CAS  Google Scholar 

  24. Clarke, D. A., F. S. Philips, S. S. Steinberg, C. C. Stock, G. B. Elion and G. H. Hitchings: Cancer Res. 13, 593 (1953).

    PubMed  CAS  Google Scholar 

  25. Clarke, D. A., F. S. Philips, S. S. Steinberg,and C. C. Stock: Ann. N. Y. Acad. 60, 235 (1954).

    CAS  Google Scholar 

  26. Skipper, H. E.: Ann. N. Y. Acad. Sci. 60, 268 (1954).

    Google Scholar 

  27. Skipper, H. E,. J. R. Thomson, G. B. Elion and G. H. Hitchings: Cancer Res. 14, 294 (1954).

    PubMed  CAS  Google Scholar 

  28. Law, L. W., V. Taormina and P. J. Boyle: Ann. N. Y. Acad. Sci. 60, 244 (1954).

    PubMed  CAS  Google Scholar 

  29. Gellhorn, H., and E. Hirschberg: Cancer Res. Suppl. 3, 1 (1955).

    Google Scholar 

  30. Burchenal, J. H., M. L. Murphy, R. R. Ellison, M. P. Sykes, T. C. Lan, L. A. Leone, D. A. Karnofsky, L. F. Carver, H. W. Dargeon and C. P. Rhoads: Blood 8, 965 (1953).

    PubMed  CAS  Google Scholar 

  31. Hitchings, G. H., and C. P. Rhoads: Ann. N. Y. Acad. Sci. 60, Art. 2 (1954).

    Google Scholar 

  32. Elion, G. B., and G. H. Hitchings: J. biol. Chem. 192, 505 (1951).

    PubMed  CAS  Google Scholar 

  33. Elion, G. B., S. Singer, and G. H. Hitchings: J. biol. Chem. 204, 35 (1953).

    PubMed  CAS  Google Scholar 

  34. Elion, G. B., S. Singer, and G. H. Hitchings M. E. Balis and G. B. Brown: 202, 647 (1953).

    Google Scholar 

  35. Elion, G. B. and G. H. Hitchings: The chemistry and biology of purines. Ciba Foundation Symposium. Boston: Little, Brown and Co.

    Google Scholar 

  36. Skipper, H. E.: Ann. N. Y. Acad Sci 60, 315 (1954).

    PubMed  CAS  Google Scholar 

  37. Clarke, D. A., F. S. Philips, C. C. Stock, G. B. Elion and G. H. Hitchings: Abstracts, 125th Meeting Amer. Chem Soc., Kansas City, p. 12 M (1954).

    Google Scholar 

  38. Hitchings, G. H.: Amer. J. Clin. Nutr. 3, 321 (1955).

    PubMed  CAS  Google Scholar 

  39. Hartman, S. C., B. Levenberg and J. M. Buchanan: J. Amer. chem. Soc. 77, 501 (1955).

    CAS  Google Scholar 

  40. Brown, G. B., and V. C. Weliky: J. biol. Chem. 204, 1019 (1953).

    PubMed  CAS  Google Scholar 

  41. Biesele, J. J., M. C. Slaulterbuck and M. Margolis: Cancer 8, 87 (1955).

    PubMed  CAS  Google Scholar 

  42. Wheeler, G. P., and H. E. Skipper: J. biol. Chem. 205, 749 (1953).

    PubMed  CAS  Google Scholar 

  43. Elion, G. B., H. Vanderwerff, G. H. Hitchings, M. E. Balis, D. H. Levin and G. B. Brown: J. biol. Chem. 200, 7 (1953).

    PubMed  CAS  Google Scholar 

  44. Remy, C. N., and M. S. Smith: J. biol. Chem. 228, 325 (1957).

    PubMed  CAS  Google Scholar 

  45. Kornberg, A., and W. E. PriserJr.: J. biol. Chem. 193, 481 (1951).

    PubMed  CAS  Google Scholar 

  46. Weygand, F., A. Wacker and H. Dellweg: Z. Naturforsch. 7 B, 19 (1952).

    Google Scholar 

  47. Bendich, A., H. B. Pahl and G. B. Brown: The McCollum Pratt Symposium “The chemical basis of heredity”. Baltimore: Johns Hopkins Press 1957.

    Google Scholar 

  48. Litman, R. M., and A. B. Pardee: Nature (Lond.) 178, 529 (1956).

    CAS  Google Scholar 

  49. Mathews, R. E. F.: Bact. Rev. 10, 359 (1958).

    Google Scholar 

  50. Zamenhof, S., R. Degiovanni and K. Rich: J. Bact. 71, 60 (1956).

    PubMed  CAS  Google Scholar 

  51. Zamenhof, S. and G. Griboff: Nature (Lund.) 174, 307 (1954).

    CAS  Google Scholar 

  52. Luzatti, D.: C. R. Acad. Sci. (Paris) 245, 1466 (1957).

    Google Scholar 

  53. Hitchings, G. H., G. B. Elion and E. A. Falco: J. biol. Chem. 185, 643 (1950).

    PubMed  CAS  Google Scholar 

  54. Hitchings, G. H., G. B. Elion and H. Vanderwerff: 174, 1037 (1948).

    Google Scholar 

  55. Heidelberger, C., N. K. Chaudhuri, P. Danneberg, D. Mooren, L. Griesbach, R. Duschinsky, R. J. Schnitzer, E. Pleven and J. Schreiner: Nature (Lond.) 179, 663 (1957).

    CAS  Google Scholar 

  56. Heidelberger, C., L. Griesbach, B. J. Montog, D. Mooren, O. Cruz, R. J. Schnitzer and E. Grunberg: Cancer Res. 18, 305, 318, 329 (1958).

    Google Scholar 

  57. Eidenoff, M. L., J. E. Knoll and D. Klein: Arch. Biochem. Biophys. 71, 274 (1957).

    Google Scholar 

  58. Cohen, S. S., J. G. Flaks, H. D. Barner, M. R. Loeb and J. Lichtenstein: PTOC. nat. Acad. Sci. (Wash.) 44, 1004 (1958).

    CAS  Google Scholar 

  59. Prusoff, W. N.: J. biol. Chem. 226, 901 (1957).

    PubMed  CAS  Google Scholar 

  60. Handschuhmacher, R. E.: Fed. Proc. 16, 191 (1957).

    Google Scholar 

  61. Prusoff, W. H., L. G. Lajtha and A. D. Welch: Biochim. biophys. Acta 20, 209 (1956).

    CAS  Google Scholar 

  62. Handschumacher, R. E., and A. D. Welch: Cancer Res. 16, 965 (1956).

    PubMed  CAS  Google Scholar 

  63. Welch, A. D., R. E. Handschumacher and J. J. Jaffe: Proc. Amer. Cancer Res. 2, 259 (1957).

    Google Scholar 

  64. Skoda, J., V. F. Hess and F. Sorm: Chem. Listy 51, 1194 (1957).

    CAS  Google Scholar 

  65. Handschumacher, R. E.: Biochim. biophys. Acta 23, 428 (1957).

    PubMed  CAS  Google Scholar 

  66. Handschumacher, R. E. and C. A. Pasternak: Biochim. biophys. Acta 30, 451 (1958).

    CAS  Google Scholar 

  67. Skode, J., and F. Sorm: Biochim. biophys. Acta 28, 660 (1958).

    Google Scholar 

  68. Munro, H. N., and C. M. Clark: Biochim. biophys. Acta 27, 648 (1958).

    CAS  Google Scholar 

  69. Rabinovitz, M., M. E. Olson and D. M. Greenberg: J. biol. Chem. 210, 837 (1956).

    Google Scholar 

  70. Mcfall, E., A. B. Pardee and G. S. Stent: Biochim. biophys. Acta 27, 282 (1958).

    CAS  Google Scholar 

  71. Munier, R., and G. N. Cohen: Biochim. biophys. Acta 21, 592 (1956).

    CAS  Google Scholar 

  72. Cohen, G. N., and E. A. Adelberg: J. Bact. 76, 328 (1958).

    PubMed  CAS  Google Scholar 

  73. Adelberg, E. A.: J. Bact. 76, 326 (1958).

    PubMed  CAS  Google Scholar 

  74. Sharon, N., and F. Lipmann: Arch. Biochem. 69, 219 (1957).

    PubMed  CAS  Google Scholar 

  75. Pardee, A. B., V. G. Shore and L. S. Prestidge :Biochim. biophys. Acta 21, 406 (1956)

    PubMed  CAS  Google Scholar 

  76. Brawerman, G., and M. Yeas: Arch. Biochem. 68, 112 (1957).

    PubMed  CAS  Google Scholar 

  77. Pardee, A. B., and L. S. Prestidge: Biochim. biophys. Acta 27, 330 (1958).

    CAS  Google Scholar 

  78. Gross, D., and H. Tarver: J. biol. Chem. 217, 169 (1955).

    PubMed  CAS  Google Scholar 

  79. Tarver, H., and D. Gross: Fed. Proc. 14, 291 (1955).

    Google Scholar 

  80. Levine, M., and H. Tarver: J. biol. Chem. 192, 835 (1957).

    Google Scholar 

  81. Berg, P.: J. biol. Chem. 222, 1025 (1956).

    PubMed  CAS  Google Scholar 

  82. Stekol, J. A., and L. Weiss: J. biol. Chem. 185, 577 (1950).

    PubMed  CAS  Google Scholar 

  83. Channon, H. J., and J. A. Smith: Biochem. J. 30, 115 (1936).

    PubMed  CAS  Google Scholar 

  84. Moyer, A. W., and V. Du Vigneaud: J. biol. Chem. 143, 373 (1942).

    CAS  Google Scholar 

  85. Mcconnell, K. P., and B. J. Cooper: J. biol. Chem. 183, 459 (1950).

    CAS  Google Scholar 

  86. Mcconnell, K. P. and C. H. Wabnitz: J. biol. Chem. 226, 765 (1957).

    PubMed  Google Scholar 

  87. Cowie, D. B., and G. N. Cohen: Biochim. biophys. Acta 26, 252 (1957).

    CAS  Google Scholar 

  88. Fels, I. G., and V. H. Cheldelin: Arch. Biochem. 22, 323 (1949).

    PubMed  CAS  Google Scholar 

  89. Fels, I. G., and V. H. Cheldelin: J. biol. Chem. 185, 803 (1950).

    PubMed  CAS  Google Scholar 

  90. Fels, I. G., and V. H. Cheldelin: J. biol. Chem. 176, 819 (1948).

    PubMed  CAS  Google Scholar 

  91. Peters, R. A.: Advanc. Enzymol. 18, 113 (1957).

    CAS  Google Scholar 

  92. Liebecq, C., and R. A. Peters: Biochem. biophys. Acta 3, 215 (1949).

    CAS  Google Scholar 

  93. Liebecq, C., and R. A. Peters: J. Physiol. 108, 11 P (1949).

    Google Scholar 

  94. Martins, C.: Liebigs Ann. Chem. 561, 227 (1949).

    Google Scholar 

  95. Buffa, P., R. A. Peters and R. W. Wakelin: Biochem. J. 48, 467 (1951).

    PubMed  CAS  Google Scholar 

  96. Buffa, P., R. A. Peters: Nature (Lond.) 163, 914 (1949).

    CAS  Google Scholar 

  97. Peters, R. A., R. W. Wakelin and P. Buffa: Proc. roy. Soc. B 140, 497 (1953).

    CAS  Google Scholar 

  98. Brady, R. O.: J. biol. Chem. 217, 213 (1955).

    PubMed  CAS  Google Scholar 

  99. Marcus, A., and W. B. Elliott: J. biol. Chem. 218, 823 (1956).

    PubMed  CAS  Google Scholar 

  100. Peters, R. A.: Johns Hopk. Hosp. Bull. 97, 21 (1955).

    CAS  Google Scholar 

  101. Cramer, F. B., and G. F. Woodward: J. Franklin Inst. 253, 354 (1952).

    CAS  Google Scholar 

  102. Woodward, G. E., and M. T. Hudson: Cancer Res. 14, 599 (1954).

    PubMed  CAS  Google Scholar 

  103. Wick, A. N., D. R. Drury, H. I. Naeada and J. B. Wolfe: J. biol. Chem. 224, 963 (1957).

    PubMed  CAS  Google Scholar 

  104. Serif, G. S., and A. N. Wick: J. biol. Chem. 233, 559 (1958).

    PubMed  CAS  Google Scholar 

  105. Rafelson, M. E., Jr., R. J. Winzler and H. E. Pearson: J. biol. Chem. 181, 583 (1949).

    PubMed  CAS  Google Scholar 

  106. Rafelson, M. E., H. E. Pearson and R. J. Winzler: Arch. Bio:hem. 29, 69 (1950).

    CAS  Google Scholar 

  107. Rafelson, M. E., H. E. Pearson and R. J. Winzler: Proc. Soc. exp. Biol. (N. Y.) 76, 689 (1951)

    CAS  Google Scholar 

  108. Tamm, I.: Eighth Symposium of the Soc. for Gen. Microbiol. “The Strategy of Chemotherapy”. Cambridge 1958.

    Google Scholar 

  109. Sistrom, WM. R.: Biochem. biophys. Acta 29, 579 (1958).

    PubMed  CAS  Google Scholar 

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H. Schwiegk F. Turba

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Binkley, S.B. (1961). Isotopes in studies with antimetabolites. In: Schwiegk, H., Turba, F. (eds) Radioactive Isotopes in Physiology Diagnostics and Therapy / Künstliche Radioaktive Isotope in Physiologie Diagnostik und Therapie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-49762-9_32

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