Enantiomer Effects of Huperzine A on the Aryl Acylamidase Activity of Human Cholinesterases
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
1. Acetylcholinesterase (AChE, EC 220.127.116.11) and butyrylcholinesterase (BuChE, EC 18.104.22.168) are serine hydrolase enzymes that catalyze the hydrolysis of acetylcholine.
2. (−) Huperzine A is an inhibitor of AChE and is being considered for the treatment of Alzheimer's disease.
3. In addition to esterase activity, AChE and BuChE have intrinsic aryl acylamidase activity.
4. The function of aryl acylamidase is unknown but has been speculated to be important in Alzheimer pathology.
5. Kinetic effects of (−) huperzine A and ( ±)$ huperzine A on the aryl acylamidase activity of human cholinesterases were examined.
6. (−) Huperzine A inhibited the aryl acylamidase activities of both AChE and BuChE.
7. (±) Huperzine A inhibited this function in AChE but stimulated BuChE aryl acylamidase suggesting that the (+) enantiomer is a powerful activator of this enzyme activity.
8. The two huperzine enantiomers may prove to be useful tools to examine the function of aryl acylamidase activity, including its role in Alzheimer pathology.
- Ariel, N., Ordentlich, A., Barak, D., Bino, T., Velan, B., and Shafferman, A. (1998). The ‘aromatic patch’ of three proximal residues in the human acetylcholinesterase active centre allows for versatile interaction modes with inhibitors. Biochem. J. 335:95–102.
- Ashani, Y., Grunwald, J., Kronman, C., Velan, B., and Shafferman, A. (1994). Role of tyrosine 337 in the binding of huperzine A to the active site of human acetylcholinesterase. Mol. Pharmacol. 45:555–560.
- Ashani, Y., Peggins, J. O., III, and Doctor, B. P. (1992). Mechanism of inhibition of cholinesterases by huperzine A. Biochem. Biophys. Res. Commun. 184:719–726.
- Ayer, W. A., Browne, L. M., Orszanska, H., Valenta, Z., and Liu, J.-S. (1989). Alkaloids of Lycopodium selago. On the identity of selagine with huperzine A and the structure of a related alkaloid. Can. J. Chem. 67:1538–1540.
- Bai, D. L., Tang, X. C., and He, X. C. (2000). Huperzine A, a potential therapeutic agent for treatment of Alzheimer's disease. Curr. Med. Chem. 7:355–374.
- Ballard, C. G. (2002). Advances in the treatment of Alzheimer's disease: Benefits of dual cholinesterase inhibition. Eur. Neurol. 47:64–70.
- Bartus, R.T. (2000). On neurodegenerative diseases, models, and treatment strategies: Lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp. Neurol. 163:495–529.
- Bartus, R. T., Dean, R. L. I., Beer, B., and Lippa, A. S. (1982). The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–417.
- Costagli, C., and Galli, A. (1998). Inhibition of cholinesterase-associated aryl acylamidase activity by anticholinesterase agents: Focus on drugs potentially effective in Alzheimer's disease. Biochem. Pharmacol. 55:1733–1737.
- Coyle, J. T., Price, D. L., and DeLong, M. R. (1983). Alzheimer's disease: A disorder of cortical cholinergic innervation. Science 219:1184–1190.
- Darvesh, S., Kumar, R., Roberts, S., Walsh, R., and Martin, E. (2001). Butyrylcholinesterase-mediated enhancement of the enzymatic activity of trypsin. Cell. Mol. Neurobiol. 21:285–289.
- Darvesh, S., Walsh, R., and Martin, E. (2002). Enantiomer-specific inhibition of cholinesterases by huperzine A: 8th International Conference on Alzheimer's disease and related disorders in Stockholm, Sweden. Neurobiol. Aging 23:S113.
- Ellman, G. L., Courtney, K. D., Andres, V. J., and Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7:88–95.
- Francis, P. T., Palmer, A. M., Snape, M., and Wilcock, G. K. (1999). The cholinergic hypothesis of Alzheimer's disease: A review of progress. J. Neurol. Neurosurg. Psychiatry 66:137–147
- Fujimoto, D. (1976). Serotonin-sensitive aryl acylamidase activity of acetylcholinesterase. FEBS Lett. 71:121–123.
- George, S. T., and Balasubramanian, A. S. (1982). The aryl acylamidases and their relationship to cholinesterases in human serum, erythrocyte and liver. Eur. J. Biochem. 121%:177–186.
- Giacobini, E. (2000). Cholinesterase inhibitors: From the Calabar bean to Alzheimer therapy. In Giacobini, E. (ed.), Cholinesterases and Cholinesterase Inhibitors, Martin Dunitz, London, pp. 181–226.
- Greig, N. H., Utsuki, T., Yu, Q., Zhu, X., Holloway, H. W., Perry, T., Lee, B., Ingram, D. K., and Lahiri, D. K. (2001). A new therapeutic target in Alzheimer's disease: Attention to butyrylcholinesterase. Curr. Med. Res. Opin. 17:159–165.
- Grutzendler, J., and Morris, J. C. (2001). Cholinesterase inhibitors for Alzheimer's disease. Drugs 61:41–52.
- Guillozet, A. L., Smiley, J. F., Mash, D. C., and Mesulam, M. M. (1997). Butyrylcholinesterase in the life cycle of amyloid plaques. Ann. Neurol. 42:909–918.
- Krall, W. J., Sramek, J. J., and Cutler, N. R. (1999). Cholinesterase inhibitors: A therapeutic strategy for Alzheimer disease. Ann. Pharmacother. 33:441–450.
- Liu, J. S., Zhu, Y. L., Yu, C. M., Zhou, Y. Z., Han, Y. Y., Wu, F. W., and Qi, B. F. (1986). The structures of huperzine A and B, two new alkaloids exhibiting anticholinesterase activity. Can. J. Chem. 64%:837–841.
- McKinney, M., Miller, J. H., Yamada, F., Tuckmantel, W., and Kozikowski, A. P. (1991). Potencies and stereoselectivities of enantiomers of huperzine A for inhibition of rat cortical acetylcholinesterase. Eur. J. Pharmacol. 203:303–305.
- Mesulam, M. M., and Geula, C. (1994). Butyrylcholinesterase reactivity differentiates the amyloid plaques of aging from those of dementia. Ann. Neurol. 36:722–727.
- Op Den Velde, W., and Stam, F. C. (1976). Some cerebral proteins and enzyme systems in Alzheimer's presenile and senile dementia. J. Am. Geriatr. Soc. 24:12–16.
- Perry, E. K., Perry, R. H., Blessed, G., and Tomlinson, B. E. (1978). Changes in brain cholinesterases in senile dementia of the Alzheimer type. Neuropathol. Appl. Neurobiol. 4:273–277.
- Saxena, A., Redman, A. M., Jiang, X., Lockridge, O., and Doctor, B. P. (1997). Differences in active site gorge dimensions of cholinesterases revealed by binding of inhibitors to human butyrylcholinesterase. Biochemistry 36:14642–14651.
- Silver, A. (1974). The Biology of Cholinesterases, Elsevier, Amsterdam.
- Valenta, Z., Yoshimura, H., Rogers, E. F., Ternbah, M., and Wiesner, K. (1960). The structure of selagine. Tetrahedron Lett. 10%:26–33.
- Wang, Y. E., Yue, D. X., and Tang, X. (1986). Anti-cholinesterase activity of huperzine A. Acta Pharmachol. Sinica 7:110–113.
- Yoshimura, H., Valenta, Z., and Wiesner, K. (1960). A rigorous proof of the selagine structure. Tetrahedron Lett. 12:14–17.
- Enantiomer Effects of Huperzine A on the Aryl Acylamidase Activity of Human Cholinesterases
Cellular and Molecular Neurobiology
Volume 23, Issue 1 , pp 93-100
- Cover Date
- Print ISSN
- Online ISSN
- Kluwer Academic Publishers-Plenum Publishers
- Additional Links
- aryl acylamidase
- enzyme kinetics
- huperzine A
- Industry Sectors
- Author Affiliations
- 1. Department of Medicine (Neurology and Geriatric Medicine), Dalhousie University, Halifax, Nova Scotia, Canada
- 2. Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada
- 3. Department of Chemistry, Mount Saint Vincent University, Halifax, Nova Scotia, Canada