Skip to main content
Log in

The conversion of lysine into piperidine, cadaverine, and pipecolic acid in the brain and other organs of the mouse

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The biosynthesis of piperidine, a possible neuromodulator, and its presumed precursors cadaverine and pipecolic acid, has been investigated in the mouse under in vitro conditions. Conversion of lysine into piperidine was observed only in the intestines and is probably caused by the intestinal flora. Formation of cadaverine and pipecolic acid from lysine was observed in the brain, liver, kidney, and large intestine. In addition, pipecolic acid was formed in the heart. The possible contributions of the diet and of the intestinal bacteria to the endogenous pool(s) of piperidine are discussed.

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

Access this article

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. Abood, L. G., Rinaldi, F., andEagleton, V. 1961. Distribution of piperidine in the brain and its possible significance in behavior. Nature 19:201–202.

    Google Scholar 

  2. Bohn, M., andGiacobini, E. 1974. Unpublished results.

  3. Battersby, A. R., 1961. Alkaloid biosynthesis. Q. Rev. 15:259–286.

    Google Scholar 

  4. Blau, K. 1961. Chromatographic methods for the study of amines from biological material. Biochem. J. 80:193–200.

    Google Scholar 

  5. Barsuhn, C. 1976. The measurement of nanogram amounts of piperidine in tissue by gas chromatography. Life Sci. 18:419–422.

    Google Scholar 

  6. Bachrach, U. 1973). Function of Naturally Occurring Polyamines, Academic Press, New York.

    Google Scholar 

  7. Brieger, L. 1885. Weitere Untersuchungen uber Ptomaine, Aug. Hirschwald, Berlin.

    Google Scholar 

  8. Blaschko, H., Friedman, P. J., Hawes, R., andNilsson, K. 1969. The amine oxidases of mammalian plasma. J. Physiol. 145: 384–404.

    Google Scholar 

  9. Boulanger, P., Osteux, R., Sacquet, E., andCharlier, H. 1969. La degradation de lal-lysine chez le rat “germ-free”. Biochim. Biophys. Acta 184:338–344

    Google Scholar 

  10. Borsook, H., Deasy, C. L., Haagen-Smit, A. J., Keighley, G., andLowy, P. H. 1948. The degradation of α-aminoadipic acid in guinea pig liver homogenate. J. Biol. Chem. 176:1395–1400.

    Google Scholar 

  11. Creveling, C. R., Kondo, D., andDaly, J. W. (1968). Use of dansyl derivatives and mass spectrometry for identification of biogenic amines. Clin. Chem. 14:302–309.

    Google Scholar 

  12. Cohen, S. S. 1971 Introduction to the Polyamines, Prentice Hall, Englewood Cliffs, New Jersey.

    Google Scholar 

  13. Chang, Y. F. 1976. Pipecolic acid pathway: The major lysine metabolic route in the rat brain. Biochim. Biophys. Res. Commun. 69:174–180.

    Google Scholar 

  14. Cushny, A. R. (1896). On the action of piperidine and some of its compounds. J. Exp. Med. 1:202–210.

    Google Scholar 

  15. Dolezalova, H., Stepita-Klauco, M., Fairweather, R. 1974. The accumulation of piperidien in the brain of dormant snails. Brain Res. 72: 115–122.

    Google Scholar 

  16. De Marco C., andMondovi, B. 1960. Identification of δ-aminovalerianic acid in the urine of rats injected with cadaverine. Ital. J. Biochem. 9:226–232.

    Google Scholar 

  17. Dolezalova, H., Giacobini, E., Seiler, N., andSchneider, H. H. 1973. Determination of piperidine in snail brain (Helix pomatia). Brain Res. 55:242–243.

    Google Scholar 

  18. Euler, U. S. v. 1944. Identification of a urine base with nicotine-like action. Nature 154:17.

    Google Scholar 

  19. Euler, U. S. v. 1944. Piperidine as a normal pressor constituent of human urine. Acta Physiol. Scand. 8:380–384.

    Google Scholar 

  20. Giacobini, E. 1976. Piperidine: A neuromodulator or a hypnogenic substance?In E. Costa, E. Giacobini, andR. Paoletti (eds.), New First and Second Messengers in Nervous Tissues, Raven Press, New York.

    Google Scholar 

  21. Gale, E. F. 1946. The bacterial amino acid decarboxylases. Adv. Enzymol. 6:1–32.

    Google Scholar 

  22. Guggenheim, M. 1951. Die biogenen Amine, Karger, Basel.

    Google Scholar 

  23. Greenberg, J. P., andWinitz, M. 1961. Iminoacids. Pages 2529–2558,in Chemistry of the Amino acids, Vol. 3, Wiley, New York.

    Google Scholar 

  24. Grove, J., andHenderson, L. M. 1968. The metabolism ofd-andl-lysine in the intact rat, perfused liver and liver mitochondria. Biochim. Biophys. Acta 165:113–120.

    Google Scholar 

  25. Grove, J. A., Gilbertson, T. J., Hammerstedt, R. H., andHenderson, L. M. 1969. The metabolism ofd- andl-lysine specifically labeled with 15N. Biochim. Biophys. Acta 184:329–337.

    Google Scholar 

  26. Gatfield, P. D., Taller, E., Hinton, G. G., Wallace, A. C., Abdelhour, G. M., andHaust, M. D. 1968. Hyperpipecolatemia: A new metabolic disorder associated with neuropathy and hepatomegaly. Can. Med. Assoc. J. 99:1215–1233.

    Google Scholar 

  27. Ghadami, H., Chou, W. S., andKesner, L. 1971. Biosynthesis of saccharopine and pipecolic acid froml-and,D,L-14C-lysine by human and dog liverin vitro, Biochem. Med. 5:56–66.

    Google Scholar 

  28. Gatfield, P. D., andTaller, E. 1971. Accumulation of lysine dipeptides in the brain in hyperpipecolatemia. Brain Res. 29:170–174.

    Google Scholar 

  29. Honegger, C. G., andHonegger, R. 1960. Volatile amines in brain. Nature 185:530–532.

    Google Scholar 

  30. Higashino, K., Fujioka, M., andYamamura, Y. 1971. The conversion ofl-lysine into saccharopine and α-aminoadipate in mouse. Arch. Biochim. Biophys. 142:606–614.

    Google Scholar 

  31. Hutzler, J., andDancis, J. 1968. Conversion of lysine into saccharopine by human tissue. Biochim. Biophys. Acta 158:62–69.

    Google Scholar 

  32. Hutzler, J., andDancis, J. 1975. Lysine-ketoglutarate reductase in human tissue. Biochim. Biophys. Acta 377: 42–51.

    Google Scholar 

  33. Himwich, W. A., andAgrawal, H. C. 1969. Amino acids. Page 33,in Lajtha, A. (ed.), Handbook of Neurochemistry, Vol. 1, Plenum Press, New York.

    Google Scholar 

  34. Higashino, K. andLieberman, I. 1965. Lysine catabolism by liver after partial hepatectomy. Biochim. Biophys. Acta 111:346–348.

    Google Scholar 

  35. Henningson, S., Persson, L., andRosengren, E. 1976. Biosynthesis of cadaverine in mice under influence of an anabolic steroid. Acta Physiol. Scan. 98:445–449.

    Google Scholar 

  36. Kase Y., Kataoka, M. andMiyata, T. 1967.In vitro production of piperidine from pipecolic acid in the presence of brain tissue. Life Sci. 6:2427–2431.

    Google Scholar 

  37. Kase, Y., Yamanishi, Y., Kataoka, M., Kitahara, K. andMiyata, T. 1970.In vivo production of piperidine from pipecolic acid in the rat. Part II. Life Sci. 9:1381–1387.

    Google Scholar 

  38. Kase, Y., Okano, Y., Miyata, T., Kataoka, M., andYonehara, N. 1974. The production of piperidine from pipecolic acid in the rat brain. Life Sci. 14:785–791.

    Google Scholar 

  39. Kase, Y., Kataoka, M., Miyata, T., andOkano, Y. 1973. Pipecolic acid in the dog brain. Life Sci. 13:867–873.

    Google Scholar 

  40. Kase, Y., andMiyata, T. 1976. Neurobiology of Piperidine: Its revelance to CNS function.In,Costa,E.,Giacobini,E., andPaoletti,R. (eds), New First and Second Messengers in Nervous Tissues, Advances in Biochemistry and Psychopharmacology, Vol. 15, Raven Press, New York.

    Google Scholar 

  41. Schneider, H. H. 1974. Versuche zur Bestimmung von Piperidine im Säugerorganismus. Ph.D. Thesis, University Frankfurt, Germany.

    Google Scholar 

  42. Leistner, E., andSpenser, I. D. 1973. Biosynthesis of the piperidine nucleus. Incorporation of chirally labeled [1-3H]cadaverine. J. Am. Chem. Soc. 95:4715–4725.

    Google Scholar 

  43. Lajtha, A., andSershen, H. 1974 Substrate specific uptake of diamines in mouse brain slices. Arch. Biochem. Biophys. 165:539–547.

    Google Scholar 

  44. Meister, A. 1965. Biochemistry of the Amino Acids, Academic Press, New York.

    Google Scholar 

  45. Matsumoto, I., Shinka, T., Kase, Y., andOkano, Y. 1976. Quantitative determination of piperidine in rat brain by mass fragmentography. Abstr. Int. Symp. Quant. Mass Spec. Gent, Belgium.

  46. Meek, J. L. 1974. Uptake and metabolism of piperidine and pipecolic acid in brain. Fed. Proc. Abstr. Pharmacol. 1453:468.

    Google Scholar 

  47. Morrison, R. I. 1953. The isolation ofl-pipecolic acid from Trifolium repens. Biochem. J. 53:474.

    Google Scholar 

  48. Moore, B., andRow, R. 1898 A comparison of the physiological actions and chemical constitution of piperidine, coiine and nicotine. J. Physiol. 22:273–295.

    Google Scholar 

  49. Meghal, S. K., Cheung, H. S., O'Neal, R. M., andKoeppe, R. E. 1966. Metabolism ofD,L-lysine-2-and-6-14C in rats and dogs. J. Biol. Chem. 241:2622–2625.

    Google Scholar 

  50. Miller, D. L., andRodwell, V. W. 1971 Metabolism of basic amino acids in pseudomonas putida. J. Biol. Chem. 246:2758–2764.

    Google Scholar 

  51. Dolezalova, H., andStepita-Klauco, M. 1975. Regional distribution of piperidine in the brain of waking mice. Abstr. Fifth Ann. Meet. Soc. Neurosci., New York, p. 733.

  52. Nixon, R., andSidman, R. I. 1971. Alicyclic amines in mouse brain and other tissues. Fed. Proc. 30: Abstr. 190.

  53. Nordenstrom, B. E. W. 1951. Effect of cadaverine and lysine on the urinary excretion of piperidine in rabbits. Acta Pharmacol. Toxicol. 1:287–296.

    Google Scholar 

  54. Nomura, Y., Schmidt-Glenewinkel, T., andGiacobini, E. 1977. The conversion of cadaverine and pipecolic acid into piperidine in the mouse brain and other organs (in preparation).

  55. Onodera, R., andKandatsu, M. 1975. Catabolism of lysine by mixed rumen bacteria. Agric. Biol. Chem. 39:1239–1246.

    Google Scholar 

  56. Perry, T. L., Hestrin, M., MacDougall, L., andHansen, S. 1966 Urinary amines of intestinal bacteria origin. Clin. Chim. Acta 24:116–123

    Google Scholar 

  57. Piccoli, F., andLajtha, A. 1972 Some aspects of uptake of non-metabolites in slices of mouse brain. Biochim. Biophys. Acta 225:356–369.

    Google Scholar 

  58. Perry, T. L., Hansen, S., andMacDougall, L. 1967. Amines of human whole brain. J. Neurochem. 14:775–782.

    Google Scholar 

  59. Ranganathan, D., andRanganathan, S. 1976. Art in Biosynthesis, Academic Press, New York.

    Google Scholar 

  60. Robinson, R. 1955. The Structural Relations of Natural Products, Oxford University Press.

  61. Rothstein, M., andMiller, L. L. 1953. The conversion ofl-lysine-6-C14 to pipecolic acid in the rat. J. Am. Sci. 75:4371–4372.

    Google Scholar 

  62. Rothstein, M., andMiller, L. L. 1954. The metabolism ofl-lysine-6-C14. J. Biol. Chem. 206:243–253.

    Google Scholar 

  63. Krogsgaard-Larsen, P., andJohnston, G. A. R. 1975. Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isozazoles and related componds. J. Neurochem. 25:797–802.

    Google Scholar 

  64. Russel, D. H. (ed.) 1973. Polyamines in Normal and Neoplastic Growth, Raven Press, New York.

    Google Scholar 

  65. Raina, A., andJänne, J. 1975. Physiology of natural polyamines putrescine, spermidine and spermine. Med. Biol. 53:121–147.

    Google Scholar 

  66. Seiler, N., andSchneider, H. H. 1974. Estimation of picomole quantities of piperidine in tissues. Biomed. Mass Spectrosc. 1:381–385.

    Google Scholar 

  67. Stepita-Klauco, M., andDolezalova, H. 1974. Cadaverine in the brain of axenic mice. Nature 252:158–159.

    Google Scholar 

  68. Stepita-Klauco, M., Dolezalova, H., andFairweather, R. 1974 Piperidine increase in the brain of dormant mice. Science 183:536–537.

    Google Scholar 

  69. Smith, T. A. 1971. The occurrence, metabolisms and functions of amines in plats. Biol. Rev. 46:201–241.

    Google Scholar 

  70. Stadtman, T. C. 1963. Anaerobic degradation of lysine. J. Biol. Chem. 238:2766–2772.

    Google Scholar 

  71. Seiler, N., andSchmidt-Glenewinkel, T. 1975 Regional distribution of putrescine, spermidine and spermine in relation to the distribution of RNA and DNA in the rat nervous system. J. Neurochem. 24:791–795.

    Google Scholar 

  72. Seiler, N. 1970. Use of the dansyl reaction in biochemical analysis. Meth. Biochem. Anal. 18:259–337.

    Google Scholar 

  73. Seiler, N. andWiechmann, M. 1970. TLC analysis of amines as their Dansderivatives. Pages 95–144,in Niederwieser, A., andPataki, G. (eds.), Progress in Thin Layer Chromatography and Related Methods, Vol. 1; Humphrey Science Publishers, Ann Harbor, Michigan.

    Google Scholar 

  74. Schmidt-Glenewinkel, T., Nomura, Y., andGiacobini, E. 1977. The formation of piperidine, pipecolic acid and cadaverine in mouse and chick during development (in preparation).

  75. Stevens, L. 1970. The biochemical role of naturally occurring polyamines in nucleic acid synthesis. Biol. Rev. 45:1–27.

    Google Scholar 

  76. Seiler, N., andDeckardt, K. 1976. Association of putrescine, spermidine, spermine and GABA with structural elements of brain cells. Neurochem. Res. 1:451–467.

    Google Scholar 

  77. Seiler, N., andAl-Therib, M. J. 1974. Acetyl-CoA: 1,4 Diaminobutane N-acetyl transferase occurrence in vertebrate organs and subcellular localization. Biochim. Biophys. Acta 354:206–212.

    Google Scholar 

  78. Tabor, H., andTabor, C. W. 1964. Spermidine, spermine and related amines. Pharmacol. Rev. 16:245–300.

    Google Scholar 

  79. Tabor, H., andTabor, C. W. 1972 Biosynthesis and metabolism of 1,4 diaminobutane, spermidine and related amines. Adv. Enzymol. 36:203–268.

    Google Scholar 

  80. Tabor, H., andTabor, C. W. 1976, 1,4 Diaminobutane (putrescine), spermidine and spermine. Ann. Rev. Biochem. 45:285–306.

    Google Scholar 

  81. Tabor, H. 1951. Diamine oxidase. J. Biol. Chem. 188:125–136.

    Google Scholar 

  82. Takeda, H., andHayaishi, O. 1966. Crystallinel-lysine oxygenase. J. Biol. Chem. 241:2733–2738.

    Google Scholar 

  83. Schmidt-Glenewinkel, T., Nomura, Y., andGiacobini, E. 1977. Unpublished results.

  84. Zeller, E. A. 1942. Diamine oxidase. Adv. Enzymol. 2:93–112.

    Google Scholar 

  85. Zacharias, R. M., Thompson, J. F., andSteward, F. C. 1952. The detection, isolation and identification of (−)-pipecolic acid as a constituent of plants. J. Am. Chem. Soc. 74:2949–2950.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmidt-Glenewinkel, T., Nomura, Y. & Giacobini, E. The conversion of lysine into piperidine, cadaverine, and pipecolic acid in the brain and other organs of the mouse. Neurochem Res 2, 619–637 (1977). https://doi.org/10.1007/BF00963776

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00963776

Keywords

Navigation