Archives of Pharmacal Research

, Volume 25, Issue 5, pp 643–646

Phytol, SSADH inhibitory diterpenoid ofLactuca sativa

  • Myun-Ho Bang
  • Soo Young Choi
  • Tae-O Jang
  • Sang Kook Kim
  • Oh-Shin Kwon
  • Tae-Cheon Kang
  • MooHo Won
  • Jinseu Park
  • Nam-ln Baek
Research Articles Articles

Abstract

The succinic semialdehyde dehydrogenase (SSADH) inhibitory component was isolated from the EtOAc fraction ofLactuca sativa through repeated column chromatography; then, it was identified as phytol, a diterpenoid, based on the interpretation of several spectral data. Incubation of SSADH with the phytol results in a time-dependent loss of enzymatic activity, suggesting that enzyme modification is irreversible. The inactivation followed pseudo-first-order kinetics with the second-rate order constant of 6.15 x 10-2 mM-1min-1. Complete protection from inactivation was afforded by the coenzyme NAD+, whereas substrate succinic semialdehyde failed to prevent the inactivation of the enzyme; therefore, it seems likely that phytol covalently binds at or near the active site of the enzyme. It is postulated that the phytol is able to elevate the neurotransmitter GABA levels in central nervous system through its inhibitory action on one of the GABA degradative enzymes, SSADH.

Key words

Lactuca sativa Anticonvulsant SSADH inhibition Phytol 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Baek, N.-l., Choi, S. Y., Park, J. K., Cho, S.-W., Ahn, E.-M., Jeon, S. G., Lee, B. R., Bahn, J. H., Kim, Y. K., Shon, I. H., Isolation and identification of succinic semialdehyde dehydrogenase inhibitory compound from the rhizome ofGastrodia elata Blume. Arch. Pharm. Res., 22, 219–224 (1999).CrossRefGoogle Scholar
  2. Bradford, M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal. Biochem., 72, 248–254 (1976).PubMedCrossRefGoogle Scholar
  3. Jung, M. J., Lippert, B., Metcalf, B., Bhlen, P. and Schechter, P.J., Vinyl GABA (4-amino-hex-5-enoic acid), a new irreversible inhibitor of GABA-T: effects on brain GABA metabolism in mice.J. Neurochem, 29, 797–802 (1977).PubMedCrossRefGoogle Scholar
  4. Khalil, AT., Abd El-fattah, H. and Mansour, E. S., Guaianolides fro.Lactuca saligna. Planta Medica, 57, 190–191 (1991).CrossRefGoogle Scholar
  5. Kitz, R. and Wilson, I.B., Esters of methanesulfonic acid as irreversible inhibitors of Acetylcholinesterase.J. Biol. Chem., 237, 3245–3249 (1962).PubMedGoogle Scholar
  6. Lee, B.R., Hong, J.W., Yoo, B.K., Lee, S.J., Cho, S.W. and Choi, S.Y, Bovine brain succinic semialdehyde dehydrogenase; Purification, kinetics and reactivity of lysyl residues connected with catalytic activity,Mol. Cells, 5, 611–617 (1995).Google Scholar
  7. Loscher, W., Valproate: a reappraisal of its phamacodynamic properties and mechanisms of action.Prog Neurobiol, 58, 31–59 (1999).PubMedCrossRefGoogle Scholar
  8. Olsen, R. W. and Avoli, M., GABA and epileptogenesis.Epilepsia, 38, 399–407 (1997).PubMedCrossRefGoogle Scholar
  9. Singh, B., Agrawal, P. K. and Thakur, R. S., Isolation of transphytol fromPhyllanthus niruri.Planta Medica, 57, 98 (1991).PubMedCrossRefGoogle Scholar
  10. Soka, T., Dictionary of Chinese Drugs, Shanghai Science Technology Shogaukan (Eds.), Shogakukan Press, Tokyo, pp. 2816, 1985.Google Scholar

Copyright information

© The Pharmaceutical Society of Korea 2002

Authors and Affiliations

  • Myun-Ho Bang
    • 1
  • Soo Young Choi
    • 2
  • Tae-O Jang
    • 1
  • Sang Kook Kim
    • 3
  • Oh-Shin Kwon
    • 3
  • Tae-Cheon Kang
    • 4
  • MooHo Won
    • 4
  • Jinseu Park
    • 2
  • Nam-ln Baek
    • 1
  1. 1.Graduate School of Biotechnology & Plant Metabolism Research CenterKyunghee UniversitySuwonKorea
  2. 2.Department of Genetic Engineering, Division of Life SciencesHallym UniversityChunchonKorea
  3. 3.Department of BiochemistryKyungpook National UniversityTaeguKorea
  4. 4.Department of Anatomy, College of MedicineHallym UniversityChunchonKorea
  5. 5.Graduate School of BiotechnologyKyung Hee UniversityKiheung-Eup, Yongin-Si, Kyunggi-DoKorea

Personalised recommendations