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The glycine cleavage system: Composition, reaction mechanism, and physiological significance

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Summary

The glycine cleavage system catalyzes the following reversible reaction: Glycine + THF + NAD+ ⇌ 5,10-methylene-THF + + CO2 + NH3 + NADH

Reversibility of the overall reaction was established through the studies with the enzymes prepared from liver mitochondria of rat and cock and from extracts ofArthrobacter globiformis grown on glycine. The glycine cleavage system is composed from four protein components. The four proteins were revealed to exist originally as an enzyme complex in the liver mitochondria. Partial reactions of glycine cleavage and glycine synthesis were studied in detail with partially purified individual protein components. Particularly a protein-bound intermediate of glycine metabolism could be isolated and its nature and role were clarified. A tentative scheme was presented to explain the whole process of the reversible glycine cleavage.

The glycine cleavage system was shown to represent the major pathway of catabolism of both glycine and serine in vertebrates, including mammals, birds, reptiles, amphibians, and fishes. Serine catabolism in these animals proceeds mainly by way of the cleavage of serine to form methylene-THF and glycine rather than deamination by serine dehydratase. In ureotelic and ammonotelic animals methylene-THF formed from the α-carbon of glycine as well as theβ-carbon of serine could be further oxidized to CO2 in either the mitochondria or the soluble tissue fractions, while in uricotelic animals methylene-THF could hardly be oxidized to CO2 and instead, was utilized mostly for purine synthesis. Glycine synthesis by the glycine cleavage system did not appear to have appreciable physiological significance in animals.

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Abbreviations

THF:

dl,l-tetrahydrofolic acid.

References

  1. D. M. Greenberg, “Metabolic Pathways”, ed. by D. M. Greenberg, Vol. III, p. 96. Academic Press, New York (1969).

    Google Scholar 

  2. R. D. Sagers and J. C. Gunsalus, (1961) J. Bacteriol. 81, 541.

    Google Scholar 

  3. D. A. Richert, R. Amberg and M. Wilson, (1962) J. Biol. Chem. 237, 99.

    Google Scholar 

  4. J. D. Pitts and G. W. Crosbie, (1962) Biochem. J. 83, 35P.

  5. K. M. Jones and Z. S. Bridgeland, (1966) Biochem. J. 99, 25P.

  6. W. B. McConnell, (1964) Canadian J. Biochem. 42, 1293.

    Google Scholar 

  7. E. A. Cossins and S. K. Sinha, (1966) Biochem. J. 101, 542.

    Google Scholar 

  8. H. Kawasaki, T. Sato and G. Kikuchi, (1966) Biochem. Biophys. Res. Commun. 23, 227.

    Google Scholar 

  9. T. Sato, H. Kochi, Y. Motokawa, H. Kawasaki and G. Kikuchi, (1969) J. Biochem. 65, 63.

    Google Scholar 

  10. H. Kochi and G. Kikuchi, (1969) Arch. Biochem. Biophys. 132, 359.

    Google Scholar 

  11. Y. Motokawa and G. Kikuchi, (1969) Arch. Biochem. Biophys. 135, 402.

    Google Scholar 

  12. Y. Motokawa and G. Kikuchi, (1969) J. Biochem. 65, 71.

    Google Scholar 

  13. T. Sato, H. Kochi, N. Sato and G. Kikuchi, (1969) J. Biochem. 65, 77.

    Google Scholar 

  14. Y. Motokawa, K. Hiraga, H. Kochi and G. Kikuchi, (1970) Biochem. Biophys. Res. Commun. 38, 771.

    Google Scholar 

  15. T. Yoshida and G. Kikuchi, (1972) J. Biochem. 72, 1503.

    Google Scholar 

  16. T. Yoshida and G. Kikuchi, (1973) J. Biochem. 73, No. 5.

  17. S. M. Klein and R. D. Sagers, (1966) J. Biol. Chem. 241, 197.

    Google Scholar 

  18. S. M. Klein and R. D. Sagers, (1966) J. Biol. Chem. 241, 206.

    Google Scholar 

  19. S. M. Klein and R. D. Sagers, (1967) J. Biol. Chem. 242, 297.

    Google Scholar 

  20. S. M. Klein and R. D. Sagers, (1967) J. Biol. Chem. 242, 301.

    Google Scholar 

  21. Y. Motokawa and G. Kikuchi, (1972) J. Biochem. 72, 1281.

    Google Scholar 

  22. H. Kochi and G. Kikuchi, (1972) Seikagaku 44, 485.

    Google Scholar 

  23. C. G. Mackenzie, (1955) J. Biol. Chem. 186, 351.

    Google Scholar 

  24. M. L. Baginsky and F. M. Huennekens, (1966) Biochem. Biophys. Res. Commun. 23, 600.

    Google Scholar 

  25. M. L. Baginsky and F. M. Huennekens, (1967) Arch. Biochem. Biophys. 120, 703.

    Google Scholar 

  26. Y. Motokawa and G. Kikuchi, (1971) Arch. Biochem. Biophys. 146, 461.

    Google Scholar 

  27. K. Hiraga, H. Kochi, Y. Motokawa and G. Kikuchi, (1972) J. Biochem. 72, 1285.

    Google Scholar 

  28. P. Andrews, (1964) Biochem. J. 91, 222.

    Google Scholar 

  29. D. H. Lowry, H. G. Rosebrough, A. L. Farr and R. J. Randall, (1961) J. Biol. Chem. 193, 265.

    Google Scholar 

  30. L. J. Reed and D. J. Cox, (1966) Ann. Rev. Biochem. 35, 57.

    Google Scholar 

  31. E. A. Boeker and E. E. Snell, “The Enzymes”, ed. by P. D. Boyer, Vol. VI, p. 217. Academic Press, New York (1972).

    Google Scholar 

  32. T. Yoshida, G. Kikuchi, K. Tada, K. Narisawa and T. Arakawa, (1969) Biochem. Biophys. Res. Commun. 35, 577.

    Google Scholar 

  33. K. Tada, K. Narisawa, T. Yoshida, T. Konno, Y. Yokoyama, H. Nakagawa, K. Tanno, K. Mochizuki, T. Arakawa, T. Yoshida and G. Kikuchi, (1969) Tohoku J. Exp. Med. 98, 289.

    Google Scholar 

  34. T. Yoshida and G. Kikuchi, (1970) Arch. Biochem. Biophys. 139, 380.

    Google Scholar 

  35. M. Suda and H. Nakagawa, “Methods in Enzymology” ed. by H. Tabor and C. W. Tabor, Vol. 17B, p. 346. Academic Press, New York (1971).

    Google Scholar 

  36. C. Kutzbach and E. L. R. Stokstad, (1968) Biochem. Biophys. Res. Commun. 30, 111.

    Google Scholar 

  37. T. Yoshida and G. Kikuchi, (1971) Arch. Biochem. Biophys. 145, 658.

    Google Scholar 

  38. L. Goldstein, W. E. Knox and E. J. Behrman, (1962) J. Biol. Chem. 237, 2855.

    Google Scholar 

  39. K. Bojanowska and D. H. Williamson, (1968) Biochim. Biophys. Acta 159, 560.

    Google Scholar 

  40. H. Nakagawa, H. Kimura and S. Miura, (1967) Biochem. Biophys. Res. Commun. 28, 359.

    Google Scholar 

  41. R. A. Freedland and E. H. Avery, (1964) J. Biol. Chem. 239, 3357.

    Google Scholar 

  42. T. E. Friedemann, “Methods in Enzymology”, ed. by S. P. Colowick and N. O. Kaplan, Vol. III, p. 414. Academic Press, Inc., New York (1957).

    Google Scholar 

  43. A. Nagabhushanam and D. M. Greenberg, (1965) J. Biol. Chem. 240, 3002.

    Google Scholar 

  44. E. V. Rowsell, J. A. Carnie and S. D. Wahbi, (1965) Biochem. J. 96, 13P.

  45. S. H. Mudd, J. D. Finkelstein, F. Irreverre and L. Laster, (1965) Biochem. Biophys. Res. Commun. 19, 665.

    Google Scholar 

  46. M. A. Grillo and T. Fossa, (1963) Bull. Soc. ital. Biol. sper. 39, 1199.

    Google Scholar 

  47. M. A. Grillo, T. Fossa and M. Coghe, (1970) Enzymologia, 39, 248.

    Google Scholar 

  48. N. L. Edson, H. A. Krebs and A. Model, (1936) Biochem. J. 30, 1380.

    Google Scholar 

  49. C. F. Strittmatter, (1965) J. Biol. Chem. 240, 2557.

    Google Scholar 

  50. J. L. Karlsson and H. A. Barker, (1949) J. Biol. Chem. 177, 597.

    Google Scholar 

  51. R. A. Bloomfield, A. A. Letter and R. P. Wilson, (1969) Arch. Biochem. Biophys. 129, 196.

    Google Scholar 

  52. D. S. Broderick, K. L. Candland, J. A. North and J. H. Mangum, (1972) Arch. Biochem. Biophys. 148, 196.

    Google Scholar 

  53. H. I. Nakada, B. Friedmann and S. Weinhouse, (1955) J. Biol. Chem. 216, 583.

    Google Scholar 

  54. S. Weinhouse, “A Symposium on amino acid metabolism”, ed. by D. McElroy and H. B. Glass, Johns Hopkins Univ., Baltimore, p. 637 (1955).

    Google Scholar 

  55. M. A. Schlossberg, R. J. Bloom, D. A. Richert and W. W. Westerfeld, (1970) Biochemistry, 9, 1148.

    Google Scholar 

  56. T. Saito, S. Tuboi, Y. Nishimura and G. Kikuchi, (1971) J. Biochem. 69, 265.

    Google Scholar 

  57. S. Ratner, V. Nocito and D. E. Green, (1944) J. Biol. Chem. 152, 119.

    Google Scholar 

  58. B. Childs, W. L. Nyhan, M. Borden, L. Bard and R. E. Cooke, (1961) Pediatrics 27, 522.

    Google Scholar 

  59. D. Shemin, C. S. Russell and T. Abramsky, (1955) J. Biol. Chem. 215, 613.

    Google Scholar 

  60. A. M. Nemeth, C. S. Russell and D. Shemin, (1957) J. Biol. Chem. 229, 415.

    Google Scholar 

  61. T. Ando and W. L. Nyhan, (1969) Tohoku J. Exp. Med. 99, 189.

    Google Scholar 

  62. W. L. Ryan and M. J. Carver, (1966) Nature, 212, 292.

    Google Scholar 

  63. Y. Matsuda, Y. Kuroda, K. Kobayashi and N. Katunuma, (1973) J. Biochem. 73, 291.

    Google Scholar 

  64. O. Wiss, (1949) Helv. Chim. Acta 32, 153.

    Google Scholar 

  65. H. Nakagawa, S. Miura, H. Kimura and T. Kanatsuna, (1969) J. Biochem. 66, 549.

    Google Scholar 

  66. H. R. Whiteley, (1960) Comp. Biochem. Physiol. 1, 227.

    Google Scholar 

  67. M. A. Grillo, T. Fossa and M. Coghe, (1966) Comp. Biochem. Physiol. 19, 589.

    Google Scholar 

  68. Y. Nakano, M. Fujioka and H. Wada, (1968) Biochim. Biophys. Acta 159, 19.

    Google Scholar 

  69. M. Fujioka, (1969) Biochim. Biophys. Acta 185, 383.

    Google Scholar 

  70. D. Elwyn, J. Ashmore, G. F. Chaill, S. Zottu, W. Welch and A. B. Hastings, (1957) J. Biol. Chem. 226, 735.

    Google Scholar 

  71. A. L. Kretchmar and E. J. Price, (1969) Metabolism 18, 684.

    Google Scholar 

  72. H. A. Lardy, C. M. Veneziale and F. Gabrielli, “Metab. Regul. Enzyme Action, Fed. Eur. Biochem. Soc. Meet., 6th 1969”, ed. by A. Sols, Academic Press, Inc., London, p. 55 (1970).

    Google Scholar 

  73. T. M. Chan and R. A. Freedland, (1971) Biochim. Biophys. Acta 237, 99.

    Google Scholar 

  74. H. C. Pitot, V. R. Potter and H. P. Morris, (1961) Cancer Res. 21, 1001.

    Google Scholar 

  75. H. C. Pitot and C. Peraino, (1964) J. Biol. Chem. 239, 1783.

    Google Scholar 

  76. C. Peraino and H. C. Pitot, (1964) J. Biol. Chem. 239, 4308.

    Google Scholar 

  77. C. Peraino, R. L. Blake and H. C. Pitot, (1965) J. Biol. Chem. 240, 3039.

    Google Scholar 

  78. E. Ishikawa, T. Ninagawa and M. Suda, (1965) J. Biochem. 57, 506.

    Google Scholar 

  79. C. Peraino, (1967) J. Biol. Chem. 242, 3860.

    Google Scholar 

  80. J. P. Jost, A. Hsie, S. D. Hughes and L. Ryan, (1970) J. Biol. Chem. 245, 351.

    Google Scholar 

  81. H. Inoue, C. B. Kasper and H. C. Pitot, (1971) J. Biol. Chem. 246, 2626.

    Google Scholar 

  82. G. P. Cheung, J. P. Cotropia and H. J. Sallach, (1969) Arch. Biochem. Biophys. 129, 672.

    Google Scholar 

  83. E. V. Rowsell, K. Snell, J. A. Carnie and A. H. Al-Tai, (1969) Biochem. J. 115, 1071.

    Google Scholar 

  84. T. Aikawa, H. Matsutaka, K. Takezawa and E. Ishikawa, (1972) Biochim. Biophys. Acta 279, 234.

    Google Scholar 

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  1. Departm. of Biochemistry, Tohoku University School of Medicine, 980, Sendai, Japan

    Goro Kikuchi

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Kikuchi, G. The glycine cleavage system: Composition, reaction mechanism, and physiological significance. Mol Cell Biochem 1, 169–187 (1973). https://doi.org/10.1007/BF01659328

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