Skip to main content
SpringerLink
Log in

Pteroylpolyglutamates

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Summary

Reduced derivatives of the vitamin pteroylglutamic acid (folic acid) are essential coenzymes for the biosynthesis of purine nucleotides, methionine, thymidylate and for many other enzyme catalyzed reactions involving the transfer, oxidation and reduction of single carbon units. Pteroylglutamic acid is found in tissues in the form of poly-γ-glutamyl derivatives of varying chain length. The present review covers the detection, distribution, synthesis, degradation, coenzyme function and inhibitory activities of pteroyl-γ-glutamates. The biosynthesis and inhibitory activities of poly-γ-glutamyl derivatives of methotrexate, an analog of pteroylglutamic acid having antitumor activity, are also considered. An hypothesis on the coenzymatic role of pteroylpoly-γ-glutamates in the coordination of sequential enzymatic steps in the metabolism of single carbon units is presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Blakley, R. L., 1969. The Biochemistry of Folic Acid and Related Pteridines, North-Holland Publishing Co. Amsterdam.

    Google Scholar 

  2. Baugh, C. M. & Krumdieck, C., 1971. Ann. N.Y. Acad. Sci. 186: 7–28.

    PubMed  Google Scholar 

  3. Covey, J. M., 1980. Life Sciences 26: 665–678.

    PubMed  Google Scholar 

  4. Seeger, D. R., Cosulich, D. B., Smith, J. M. Jr. & Hultquist, M. E., 1949. J. Am. Chem. Soc. 71: 1753–1758.

    Google Scholar 

  5. Ensminger, W. D., Grindley, G. B. & Hoagland, J. A., 1979. Adv. Cancer Chemotherapy 1: 62–93. (A. Rosowsky, Ed. M. Dekker).

    Google Scholar 

  6. IUPAC-IUB-Tentative Rules, 1966. J. Biol. Chem. 241: 2991–2992.

    Google Scholar 

  7. Pfiffner, J. J., Calkins, D. G., Bloom, E. S. & O'Dell, B. L., 1946. J. Am. Chem. Soc. 68: 1392–1397.

    Google Scholar 

  8. Curthoys, N. P. & Rabinowitz, J. C., 1972. J. Biol. Chem. 247: 1965–1971.

    PubMed  Google Scholar 

  9. Boothe, J. H., Mowatt, J. H., Hutchings, B. L., Angier, R. B., Waller, C. W., Stokstad, E. L. R., Semb, J., Gazzola, A. L. & Subbarow, Y., 1948. J. Am. Chem. Soc. 70: 1099–1151.

    Google Scholar 

  10. Krumdieck, C. L. & Baugh, C. M., 1969. Biochemistry 8: 1568–1572.

    PubMed  Google Scholar 

  11. Godwin, H. A., Rosenberg, I. H., Ferenz, C. R., Jacobs, P. M. & Meienhofer, J., 1972. J. Biol. Chem. 247: 2266–2271.

    PubMed  Google Scholar 

  12. Sengupta, P. K., Bieri, J. H. & Viscontini, M. 1975. Helvitca Chemica Acta 1374–1379.

  13. Kisliuk, R. L., Gaumont, Y. & Baugh, C. M., 1974. J. Biol. Chem. 249: 4100–4103.

    PubMed  Google Scholar 

  14. Krumdieck, C. L. & Baugh, C. M., 1980. Methods Enzymol. 66: 523–529.

    PubMed  Google Scholar 

  15. Matthews, R. G. & Baugh, C. M., 1980. Biochemistry 19: 2040–2045.

    PubMed  Google Scholar 

  16. Coward, J. K., Parameswaran, K. N., Cashmore, A. R. & Bertino, J. R., 1974. Biochemistry 13: 3889–3903.

    PubMed  Google Scholar 

  17. MacKenzie, R. E. & Baugh, C. M., 1980. Biochim. Biophys. Acta 611: 187–195.

    PubMed  Google Scholar 

  18. Salem, M. E., Lewis, G. P. & Rowe, P. B., 1979. Anal. Biochem. 97: 48–50.

    PubMed  Google Scholar 

  19. Friedkin, M., Plante, L. T., Crawford, E. J. & Crumm, M., 1975. J. Biol. Chem. 250: 5614–5621.

    PubMed  Google Scholar 

  20. Baggott, J. E. & Krumdieck, C., 1979. Biochemistry 18: 1036–1041.

    PubMed  Google Scholar 

  21. Cheng, F. W., Shane, B. & Stokstad, E. L. R., 1975. Can. J. Biochem. 53: 1020–1027.

    Google Scholar 

  22. Coward, J. K., Chello, P., Cashmore, A., Parameswaran, K. N., DeAngelis, L. M. & Bertino, J. R., 1975. Biochemistry 14: 1548–1551.

    PubMed  Google Scholar 

  23. Kisliuk, R. L., Gaumont, Y., Lafer, E., Baugh, C. M. & Montgomery, J. A., 1981. Biochemistry 20: 929–934.

    PubMed  Google Scholar 

  24. Maruyama, T., Shiota, T. & Krumdieck, C. L., 1978. Anal. Biochem. 84: 234–240.

    Google Scholar 

  25. Reed, B. & Scott, J.M., 1980. Methods Enzymol. 66: 501–507.

    PubMed  Google Scholar 

  26. Lewis, G. P. & Rowe, P. B., 1979. Anal. Biochem. 93: 91–97.

    PubMed  Google Scholar 

  27. Baugh, C. M., Braverman, E. B., Nair, M. G., Horne, D. W., Briggs, W. T. & Wagner, C., 1979. Anal. Biochem. 92: 366–369.

    PubMed  Google Scholar 

  28. Eto, I. & Krumdieck, C. L., 1980. Anal. Biochem. 109: 167–184.

    PubMed  Google Scholar 

  29. Foo, S. K., Cichowicz, D. J. & Shane, B., 1980. Anal. Biochem. 107: 109–115.

    PubMed  Google Scholar 

  30. Cashmore, A. R., Dreyer, R. N., Horvath, C., Knipe, J. O., Coward, J. K. & Bertino, J. R., 1980. Methods Enzymol. 66: 459–468.

    PubMed  Google Scholar 

  31. Archer, M. C. & Reed, L. S., 1980. Methods Enzymol. 66: 452–459.

    PubMed  Google Scholar 

  32. Brody, T., Shane, B. & Stokstad, E. L. R., 1979. Anal. Biochem. 92: 501–509.

    PubMed  Google Scholar 

  33. Rao, K. N. & Noronha, J. M., 1978. Anal. Biochem. 88: 128–137.

    PubMed  Google Scholar 

  34. Bird, O. D., McGlohon, V. M. & Vaitkus, J. W., 1965. Anal. Biochem. 12: 18–35.

    PubMed  Google Scholar 

  35. Wittenberg, J. B., Noronha, J. M. & Silverman, M., 1962. Biochem. J. 85: 9–15.

    PubMed  Google Scholar 

  36. Osborne-White, W. S. & Smith, R. M., 1973. Biochem. J. 136: 265–278.

    PubMed  Google Scholar 

  37. Moran, R. G., Werkheiser, W. C. & Zakrzewski, S. F., 1976. J. Biol. Chem. 251: 3569–3575.

    PubMed  Google Scholar 

  38. Scott, J. M., 1980. Methods Enzymol. 66: 437–443.

    PubMed  Google Scholar 

  39. Kas, J. & Cerna, J., 1980. Methods Enzymol. 66: 443–452.

    PubMed  Google Scholar 

  40. Rabinowitz, J. C., 1960. The Enzymes, P. D. Boyer, H. Lardy & K. Myrback, Eds., Academic Press, N.Y. Vol. 2, pp. 185–252.

  41. Priest, D. G., Happel, K. K. & Doig, M. T., 1980. J. Biochem. Biophys. Methods. 3: 201–206.

    PubMed  Google Scholar 

  42. Usdin, E., 1959. J. Biol. Chem. 234: 2373–2376.

    PubMed  Google Scholar 

  43. Hakala, M. T. & Welch, A. D., 1957. J. Bacteriol. 73: 35–40.

    PubMed  Google Scholar 

  44. Tamura, T., Shin, Y. S., Williams, M. A. & Stokstad, E. L. R., 1972. Anal. Biochem. 49: 517–521.

    PubMed  Google Scholar 

  45. Shane, B. & Stokstad, E. L. R., 1976. J. Biol. Chem. 251: 3405–3410.

    PubMed  Google Scholar 

  46. Bakerman, H. A., 1961. Anal. Biochem. 2: 558–565.

    PubMed  Google Scholar 

  47. Kozloff, L. M. & Lute, M., 1965. J. Mol. Biol. 12: 780–792.

    PubMed  Google Scholar 

  48. Kozloff, L. M., Crosby, L. K. & Baugh, C. M., 1979. J. Virol. 32: 497–506.

    PubMed  Google Scholar 

  49. Kozloff, L. M., Lute, M. & Crosby, L. K., 1979. Chemistry and Biology of Pteridines, R. L. Kisliuk & G. M. Brown, Eds., Elsevier/North-Holland, pp. 309–314.

  50. McBurney, M. W. & Whitmore, G. F., 1974. Cell 2: 173–182.

    PubMed  Google Scholar 

  51. Sirotnak, F. M., Donati, G. J. & Hutchison, D. G., 1963. J. Bacteriol. 85: 658–665.

    PubMed  Google Scholar 

  52. Iwai, K. & Nakagawa, S., 1958. Mem. Res. Inst. Food Sci. (Kyoto) 15: 49–60.

    Google Scholar 

  53. Clandinin, M. T. & Cossins, E. A., 1972. Biochem. J. 128: 29–40.

    PubMed  Google Scholar 

  54. Spronk, A. M. & Cossins, E. A., 1972. Phytochem. 11: 3157–3165.

    Google Scholar 

  55. Lor, K. L. & Cossins, E. A., 1973. Phytochem. 12: 9–14.

    Google Scholar 

  56. Cossins, E. A. & Shah, S. P. J., 1972. Phytochem. 11: 587–593.

    Google Scholar 

  57. Noronha, J. M. & Silverman, M., 1962. J. Biol. Chem. 237: 3299–3302.

    PubMed  Google Scholar 

  58. Whitehead, V. M., 1973. Lancet 743–745.

  59. Herbert, V. & Zalusky, R., 1962. J. Clin. Invest. 41: 1263–1269.

    PubMed  Google Scholar 

  60. Hintze, D. N. & Farmer, J. L., 1975. J. Bact. 124: 1236–1239.

    PubMed  Google Scholar 

  61. Baugh, C. M., Braverman, E. & Nair, M. G., 1974. Biochemistry 13: 4952–4957.

    PubMed  Google Scholar 

  62. Scott, J. M., 1976. Biochem. Soc. Trans. 4: 845–850.

    PubMed  Google Scholar 

  63. Hoffbrand, A. V., Tripp, E. & Lavoie, A., 1977. Folic Acid Nat. Acad. Sci. (U.S.A.) pp. 110–121.

  64. Brown, J. P., Davidson, G. E. & Scott, J. M., 1974. Biochim. Biophys. Acta 343: 78–88.

    PubMed  Google Scholar 

  65. Tyerman, M. J., Watson, J. E., Shane, B., Schutz, D. E. & Stokstad, E. L. R., 1977. Biochim. Biophys. Acta 497: 234–240.

    PubMed  Google Scholar 

  66. Thompson, R. W., Leichter, J., Cornwell, P. E. & Krumdieck, C. L., 1977. Am. J. Clin. Nutr. 30: 1583–1590.

    PubMed  Google Scholar 

  67. Chan, P. Y. & Cossins, E. A., 1980. Arch. Biochem. Biophys. 200: 346–351.

    PubMed  Google Scholar 

  68. Shane, B., 1980. J. Biol. Chem. 255: 5655–5662.

    PubMed  Google Scholar 

  69. Delk, A. S., Nagle, D. P., Jr. & Rabinowitz, J. C., 1980. J. Biol. Chem. 255: 4387–4390.

    PubMed  Google Scholar 

  70. Wright, B. E., 1956. J. Biol. Chem. 219: 873–883.

    PubMed  Google Scholar 

  71. Plante, L. T., Crawford, E. J. & Friedkin, M., 1976. J. Med. Chem. 19: 1295–1299.

    PubMed  Google Scholar 

  72. Dolnick, B. J. & Cheng, Y.-C., 1978. J. Biol. Chem. 253: 3563–3567.

    PubMed  Google Scholar 

  73. Powers, S. G. & Snell, E. E., 1976. J. Biol. Chem. 251: 3786–3793.

    PubMed  Google Scholar 

  74. Burton, E., Selhub, J. & Sakami, W., 1969. Biochem. J. 111: 793–795.

    PubMed  Google Scholar 

  75. Whitfield, C. D., Steers, E. J., Jr. & Weissbach, H., 1970. J. Biol. Chem. 245: 390–401.

    PubMed  Google Scholar 

  76. Jacobs, S. A., Adamson, R. H., Chabner, B. A., Derr, C. J. & Johns, D. G., 1975. Biochem. Biophys. Res. Commun. 63: 692–698.

    PubMed  Google Scholar 

  77. Whitehead, V. M., 1977. Cancer Res. 37: 408–412.

    PubMed  Google Scholar 

  78. Sirotnak, F. M., Chello, P. L., Piper, J. R. & Montgomery, J. A., 1978. Biochem. Pharm. 27: 1821–1825.

    PubMed  Google Scholar 

  79. Fernandes, D. J. & Bertino, J. R., 1980. Proc. Natl. Acad. Sci. USA 77: 5663–5667.

    PubMed  Google Scholar 

  80. DeClerq, E., Balzarini, J., Descamps, J., Bigge, C. F., Chang, C. T.-C., Kalaritis, P. & Mertes, M. P., 1981. Biochem. Pharm. 30: 495–502.

    PubMed  Google Scholar 

  81. Selhub, J., Savin, M. A., Sakami, W. & Flavin, M., 1971. Proc. Natl. Acad. Sci. USA 68: 312–314.

    PubMed  Google Scholar 

  82. Schirch, L. & Ropp, M., 1967. Biochemistry 6: 253–260.

    PubMed  Google Scholar 

  83. Krebs, H. A., Hems, R. & Tyler, B., 1976. Biochem. J. 158: 341–353.

    PubMed  Google Scholar 

  84. Kisliuk, R. L., Gaumont, Y., Baugh, C. M., Galivan, J. H., Maley, G. F. & Maley, F., 1979. Chemistry and Biology of Pteridines Kisliuk, R. L. & Brown, G. M. Eds., Elsevier/North-Holland, pp. 431–435.

  85. Taylor, R. T. & Hanna, M. L., 1977. Arch. Biochem. Biophys. 181: 331–334.

    PubMed  Google Scholar 

  86. Taylor, R. T. & Hanna, M. L., 1979. Arch. Biochem. Biophys. 197: 36–43.

    PubMed  Google Scholar 

  87. Jones, C., Kao, F.-T. & Taylor, R. T., 1980. Cytogenet. Cell. Genet. 28: 181–194.

    PubMed  Google Scholar 

  88. McGuire, J. J., Hsieh, P., Coward, J. K. & Bertino, J. R., 1980. J. Biol. Chem. 255: 5776–5778.

    PubMed  Google Scholar 

  89. Masurekar, M. & Brown, G. M., 1975. Biochemistry 14: 2424–2430.

    PubMed  Google Scholar 

  90. Gawthorne, J. M. & Smith, R. M., 1973. Biochem. J. 136: 295–301.

    PubMed  Google Scholar 

  91. Moran, R. G. & Colman, P. D., 1980. Proc. Soc. Am. Soc. Cancer Res. 21: 25.

    Google Scholar 

  92. Ferone, R. & Warskow, A., 1981. Fed. Proc. 40: 1748.

    Google Scholar 

  93. Baugh, C. M., Krumdieck, C. L. & Nair, M. G., 1973. Biochem. Biophys. Res. Commun. 52: 27–34.

    PubMed  Google Scholar 

  94. Witte, A., Whitehead, V. M., Rosenblatt, D. S. & Vuchich, M. J., 1980. Devel. Pharm. Therap. 1: 40–46.

    Google Scholar 

  95. Jacobs, S. A., Derr, J. D. & Johns, D. C., 1977. Biochem. Pharm. 26: 2310–2313.

    PubMed  Google Scholar 

  96. Nair, M. G. & Baugh, C. M., 1973. Biochemistry 12: 3923–3927.

    PubMed  Google Scholar 

  97. Whitehead, V. M., Perrault, M. M. & Stelcner, S., 1975. Cancer Res. 35: 2985–2990.

    PubMed  Google Scholar 

  98. Schilsky, R. L., Bailey, B. D. & Chabner, B. A., 1980. Proc. Natl. Acad. Sci. USA 77: 2919–2922.

    PubMed  Google Scholar 

  99. Rosenblatt, D. S., Whitehead, V. M., Vuchich, M. J., Pottier, A., Matiaszuk, N. V. & Beaulieu, D., 1981. Mol. Pharm. 19: 87–97.

    Google Scholar 

  100. Poser, R. G., Sirotnak, F. M. & Chello, P. L., 1980. Biochem. Pharm. 29: 2701–2704.

    PubMed  Google Scholar 

  101. Fry, D. W., Yalowich, J. C., Hess, M. L. & Goldman, I. D., 1981. Fed. Proc. 40: 1748.

    Google Scholar 

  102. Galivan, J. H., 1979. Cancer Res. 39: 735–743.

    PubMed  Google Scholar 

  103. Galivan, J. H., 1980. Mol. Pharm. 17: 105–110.

    Google Scholar 

  104. Gewirtz, D. A., White, J. C., Randolph, J. K. & Goldman, I. D., 1979. Cancer Res. 39: 2914–2918.

    PubMed  Google Scholar 

  105. Whitehead, V. M. & Rosenblatt, D. S., 1979. Chemistry and Biology of Pteridines, R. L. Kisliuk & G. M. Brown, Eds., Elsevier/North-Holland, pp. 689–694.

  106. Buehring, K. U. & Folsch, E., 1976. Biochim. Biophys. Acta 421: 22–32.

    PubMed  Google Scholar 

  107. Silink, M., Reddel, R., Bethel, M. & Rowe, P., 1975. J. Biol. Chem. 250: 5982–5994.

    PubMed  Google Scholar 

  108. Rosenberg, I. H. & Neumann, H., 1974. J. Biol. Chem. 249: 5126–5130.

    PubMed  Google Scholar 

  109. Rao, K. N. & Noronha, J. M., 1977. Biochim. Biophys. Acta 481: 594–607.

    PubMed  Google Scholar 

  110. Kaferstein, H. & Jaenicke, L., 1972. Hoppe-Seyler's Z. Physiol. Chem. 353: 1153–1158.

    PubMed  Google Scholar 

  111. Elsborg, L., 1980. Danish Med. Bull. 27: 205–206.

    PubMed  Google Scholar 

  112. Dawes, J. & Goldberg, E. B., 1973. Virology 55: 380–390.

    PubMed  Google Scholar 

  113. Levy, C. C. & Goldman, P., 1968. J. Biol. Chem. 243: 3507–3511.

    PubMed  Google Scholar 

  114. Albrecht, A. M., Boldizsar, E. & Hutchison, D. J., 1978. J. Bacteriol. 134: 506–513.

    PubMed  Google Scholar 

  115. Baugh, C. M., Stevens, J. C. & Krumdieck, C. L., 1970. Biochim. Biophys. Acta 212: 116–124.

    PubMed  Google Scholar 

  116. Krumdieck, C. L. & Baugh, C. M., 1970. Anal. Biochem. 35: 123–128.

    PubMed  Google Scholar 

  117. Krumdieck, C. L. & Baugh, C. M., 1980. Methods Enzymol. 66: 660–662.

    PubMed  Google Scholar 

  118. Elsenhans, B., Selhub, J. & Rosenberg, I. H., 1980. Methods Enzymol. 66: 663–667.

    PubMed  Google Scholar 

  119. Tan, L. U. L., Drury, E. J. & MacKenzie, R. E., 1977. J. Biol. Chem. 252: 1117–1122.

    PubMed  Google Scholar 

  120. Paukert, J. L., D'Ari-Strauss, L. & Rabinowitz, J. C., 1976. J. Biol. Chem. 251: 5104–5111.

    PubMed  Google Scholar 

  121. Caperelli, C. A., Benkovic, P. A., Chettur, G. & Benkovic, S. J., 1980. J. Biol. Chem. 255: 1885–1890.

    PubMed  Google Scholar 

  122. Smith, G. K., Mueller, W. T., Wasserman, G. F., Taylor, W. D. & Benkovic, S., 1980. Biochemistry 19: 4313–4321.

    PubMed  Google Scholar 

  123. Ferone, R. & Roland, S., 1980. Proc. Natl. Acad. Sci. USA 77: 5802–5806.

    PubMed  Google Scholar 

  124. Reddy, G. P. V. & Mathews, C. K., 1978. J. Biol. Chem. 253: 3641–3647.

    Google Scholar 

  125. Reddy, G. P. V. & Pardee, A. B., 1980. Proc. Natl. Acad. Sci. USA 77: 3312–3316.

    PubMed  Google Scholar 

  126. Schirch, L. & Peterson, D., 1980. J. Biol. Chem. 255: 7801–7806.

    PubMed  Google Scholar 

  127. Kovacs, J., Kapoor, U. R. G., Mayers, G. L., Giannasio, V. R., Giannotti, R., Senyk, G., Nitecki, E. & Goodman, J. W., 1972. Biochemistry 11: 1953–1958.

    PubMed  Google Scholar 

  128. Maley, G. F., Maley, F. & Baugh, C. M., 1979. J. Biol. Chem. 254: 7485–7487.

    PubMed  Google Scholar 

  129. Hiraga, K. & Kikuchi, G., 1980. J. Biol. Chem. 255: 11671–11676.

    PubMed  Google Scholar 

  130. Tabor, H. & Wyngarden, L., 1959. J. Biol. Chem. 234: 1830–1840.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Biochemistry and Pharmacology, Tufts University, 02111, Boston, MA, USA

    Roy L. Kisliuk

Authors
  1. Roy L. Kisliuk
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kisliuk, R.L. Pteroylpolyglutamates. Mol Cell Biochem 39, 331–345 (1981). https://doi.org/10.1007/BF00232583

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00232583

Keywords

Search

Navigation