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Mechanisms of acetylcholine synthesis by rat brain choline acetyltransferase and its regulation by products and inhibitors

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Drugs and Central Synaptic Transmission

Abstract

Choline acetyltransferase (EC 2.3.1.6, ChA) is the enzyme which catalyses the synthesis of acetylcholine (ACh) from acetylcoenzyme A and choline. According to available information, ChA may be bound to the outside membrane of the synaptic vesicle and so it is reasonable to assume that ACh is synthesised in the cytoplasm of the synaptosome and conveyed to the vesicle by an uptake mechanism. There is no convincing evidence, however, that there is an ACh-uptake system in the vesicular membrane (Whittaker, 1973). An alternate possibility is that the substrates choline and acetylcoenzyme A may bind to ChA from the outside surface of the vesicle, although the first product (ACh) is released towards the inside surface of the vesicle and the second product (coenzyme A) dissociates into the cytoplasm of the synaptosome. According to this alternative possibility, the presence of an ACh-uptake system is not necessary for accumulation of ACh into the vesicle. For the verification of such a possibility, we have investigated the kinetic mechanism for the synthesis of ACh by the rat brain ChA.

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References

  • Chiou, C. Y. and Sastry, B. V. R. (1968). ‘Acetylcholinesterase hydrolysis of halogen substituted acetylcholines’, Biochem. Pharmac., 17, 805–815

    Article  CAS  Google Scholar 

  • Chiou, C. Y. and Sastry, B. V. R. (1970). ‘Cholinergic activities of halogenoacetylcholines’, J. Pharmac. exp. Titer., 172, 351–366

    CAS  Google Scholar 

  • Cleland, W. W. (1970). ‘Steady state kinetics’, in The Enzymes ( Boyer, P. D., ed.) Vol. 2, 1–66, Academic Press, New York

    Google Scholar 

  • Haubrich, D. R. (1974). ‘Inhibition in vivo of acetylcholine synthesis in mouse brain by inhibitors of choline acetyltransferase’, Pharmacologist, 16, 286

    Google Scholar 

  • Henderson, G. I. and Sastry, B. V. R. (1972). ‘Rat brain choline acetyltransferase: Enzyme mechanism and inhibition by iodo-and bromoacetylcholines’, Fed. Proc. Fedn Am. Socs exp. Biol., 31, 561A

    Google Scholar 

  • Kaita, A. A. and Goldberg, A. M. (1969). ‘Control of acetylcholine synthesis. The inhibition of choline acetyltransferase by acetylcholine’, J. Neurochem., 16, 1185–1191

    Article  PubMed  CAS  Google Scholar 

  • Mahler, H. R. and Cordes, E. G (1971). Biological Chemistry 285–299, Harper and Row, New York

    Google Scholar 

  • Potter, L. T., Glover, V. A. S. and Saelens, J. K. (1968). ‘Choline acetyltransferase from rat brain’, J. Biol. Chem. 243 3864–3870

    PubMed  CAS  Google Scholar 

  • Sastry, B. V. R. and Chiou, C. Y. (1968). ‘Molecular aspects of the interactions of halogen-acetylcholines with cholinesterase’, Biochem. biophys. Acta, 167, 339–354

    PubMed  CAS  Google Scholar 

  • Sastry, B. V. R. and Henderson, G. I. (1972). ‘Kinetic mechanisms of placental choline acetyltransferase’, Biochem. Pharmac., 21, 787–802

    Article  CAS  Google Scholar 

  • Speth, R. C. and Schmidt, D. E. (1974). ‘Effects of bromoacetylcholine on rat brain acetylcholine and choline acetyltransferase’, Fedn Proc. Fedn Am. Socs exp. Biol., 33, 477

    Google Scholar 

  • White, H. L. and Cavallito, C. J. (1970). ‘Choline acetyltransferase. Enzyme mechanism and mode of inhibition by a styrylpyridine analog’, Biochim. biophys. Acta, 206, 343–357

    Article  PubMed  CAS  Google Scholar 

  • White, H. L. and Wu, J. C. (1973). ‘Kinetics of choline acetyltransferases (EC. 2.3.1.6.) from human and other mammalian central and peripheral nervous tissues’, J. Neurochem., 20, 297–307

    Article  PubMed  CAS  Google Scholar 

  • Whittaker, V. P. (1973). ‘Subcellular localization of neurotransmitters’, Adv. Cytopharmac., 1, 319–330

    Google Scholar 

  • Whittaker, V. P. (1974). ‘Molecular organization of the cholinergic vesicle’, Adv. Cytopharmac., 2, 311–317

    CAS  Google Scholar 

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Sastry, B.V.R., Henderson, G.I. (1976). Mechanisms of acetylcholine synthesis by rat brain choline acetyltransferase and its regulation by products and inhibitors. In: Bradley, P.B., Dhawan, B.N. (eds) Drugs and Central Synaptic Transmission. Palgrave, London. https://doi.org/10.1007/978-1-349-01247-3_6

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