Acetyl-l-carnitine as a precursor of acetylcholine

Abstract

Synthesis of [3H]acetylcholine from [3H]acetyl-l-carnitine was demonstrated in vitro by coupling the enzyme systems choline acetyltransferase and carnitine acetyltransferase. Likewise, both [3H] and [14C] labeled acetylcholine were produced when [3H]acetyl-l-carnitine andd-[U-14C] glucose were incubated with synaptosomal membrane preparations from rat brain. Transfer of the acetyl moiety from acetyl-l-carnitine to acetylcholine was dependent on concentration of acetyl-l-carnitine and required the presence of coenzyme A, which is normally produced as an inhibitory product of choline acetyltransferase. These results provide further evidence for a role of mitochondrial carnitine acetyltransferase in facilitating transfer of acetyl groups across mitochondrial membranes, thus regulating the availability in the cytoplasm of acetyl-CoA, a substrate of choline acetyltransferase. They are also consistent with a possible utility of acetyl-l-carnitine in the treatment of age-related cholinergic deficits.

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

References

  1. 1.

    White, H. L., and Wu, J. C. 1973. Kinetics of choline acetyl-transferases from human and other mammalian central and peripheral nervous tissues. J. Neurochem. 20:297–307.

    Google Scholar 

  2. 2.

    Tuček, S. and Cheng, S. C. 1970. Precursors of acetyl groups in acetylcholine in the brain in vivo. Biochem. Biophys. Acta 208:538–540.

    Google Scholar 

  3. 3.

    Walter U. and Söling, H. D. 1976. Transfer of acetyl-units through the mitochondrial membrane: evidence for a pathway different from the citrate pathway. FEBS Letts. 63:260–266.

    Google Scholar 

  4. 4.

    Lefresne, P., Hamon, M., Beaujouan, J. C., and Glowinski, J. 1977. Origin of the acetyl moiety of acetylcholine synthesized in rat striatal synaptosomes. Biochimie 59:197–215.

    Google Scholar 

  5. 5.

    Collier, B. 1977. Biochemistry and physiology of cholinergic transmission. Pages 463–492, in Kandel, E. R., (ed.) Handbook of Physiology, Vol. 1, Amer. Physiol. Soc., Bethesda.

    Google Scholar 

  6. 6.

    Gibson, G. E., and Shimada, M. 1980. Studies on the metabolic pathway of the acetyl group for acetylcholine synthesis. Biochem. Pharmacol. 29:167–174.

    Google Scholar 

  7. 7.

    Doležal, V., and Tuček, S. 1981. Utilization of citrate, acetyl-carnitine, acetate, pyruvate and glucose for the synthesis of acetylcholine in rat brain slices. J. Neurochem. 36:1323–1330.

    Google Scholar 

  8. 8.

    Tuček, S. 1985. Regulation of acetylcholine synthesis in the brain. J. Neurochem. 44:11–24.

    Google Scholar 

  9. 9.

    White, H. L., and Scates, P. W. 1989. Effects of acetyl-l-carnitine on acetylcholine synthesis in rat brain synaptosomes and in PC12 cells. Abstracts, Soc. for Neuroscience 15:1197.

    Google Scholar 

  10. 10.

    White, H. L., and Wu, J. C. 1973. Choline and carnitine acetyltransferases of heart. Biochemistry 12:841–846.

    Google Scholar 

  11. 11.

    Sterri, S. H., and Fonnum, F. 1980. Acetyl-CoA synthesizing enzymes in cholinergic nerve terminals. J. Neurochem. 35:249–254.

    Google Scholar 

  12. 12.

    Chase, J. F. A., and Tubbs, P. K. 1966. Some kinetic studies on the mechanism of action of carnitine acetyltransferase. Biochem. J. 99:32–40.

    Google Scholar 

  13. 13.

    Bieber, L. L. 1988. Carnitine. Ann. Rev. Biochem. 57:261–283.

    Google Scholar 

  14. 14.

    Angelucci, L., Ramacci, M. T., Taglialatela, G., Hulsebosch, C., Morgan, B., Werrbach-Perez, K., and Perez-Polo, R. 1988. Nerve growth factor binding in aged rat central nervous system: Effect of acetyl-l-carnitine. J. Neurosci. Res. 20:491–496.

    Google Scholar 

  15. 15.

    Ghirardi, O., Milano, S., Ramacci, M. T., and Angelucci, L. 1989. Long-term acetyl-L-carnitine preserves spacial learning in the senescent rat. Prog. Neuropsychopharmacol. & Biol. Psychiat. 13:237–245.

    Google Scholar 

  16. 16.

    Ramacci, M. T., DeRossi, M., Lucreziotti, M. R., Mione, M. C., and Amenta, F. 1988. Effect of long-term treatment with acetyl-L-carnitine on structural changes of aging rat brain. Drugs Exptl. Clin. Res. XIV 9:593–601.

    Google Scholar 

  17. 17.

    Curti, D., Dagani, G., Galmozzi, M. R., and Marzatico, F. 1989. Effect of aging and acetyl-l-carnitine on energetic and cholinergic metabolism in rat brain regions. Mech. of Aging and Dev. 47:39–45.

    Google Scholar 

  18. 18.

    Cucinotta, D., Passeri, M., Ventura, S., Iannuccelli, M., Senin, U., Bonati, P. A., and Parnetti, L. 1988. Multicenter clinical placebo-controlled study with acetyl-l-carnitine (LAC) in the treatment of mildly demented elderly patients. Drug Dev. Res. 14:213–216.

    Google Scholar 

  19. 19.

    Burlina, A. P., Sershen, H., Debler, E. A., and Lajtha, A. 1989. Uptake of acetyl-l-carnitine in the brain. Neurochem. Res. 14:489–493.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

White, H.L., Scates, P.W. Acetyl-l-carnitine as a precursor of acetylcholine. Neurochem Res 15, 597–601 (1990). https://doi.org/10.1007/BF00973749

Download citation

Key Words

  • Choline acetyltransferase
  • carnitine acetyltransferase
  • acetylcholine synthesis
  • synaptosomes