Mechanisms of acetylcholine synthesis by rat brain choline acetyltransferase and its regulation by products and inhibitors
Choline acetyltransferase (EC 18.104.22.168, 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.
Unable to display preview. Download preview PDF.
- Chiou, C. Y. and Sastry, B. V. R. (1970). ‘Cholinergic activities of halogenoacetylcholines’, J. Pharmac. exp. Titer., 172, 351–366Google Scholar
- Cleland, W. W. (1970). ‘Steady state kinetics’, in The Enzymes ( Boyer, P. D., ed.) Vol. 2, 1–66, Academic Press, New YorkGoogle Scholar
- Haubrich, D. R. (1974). ‘Inhibition in vivo of acetylcholine synthesis in mouse brain by inhibitors of choline acetyltransferase’, Pharmacologist, 16, 286Google 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, 561AGoogle Scholar
- Mahler, H. R. and Cordes, E. G (1971). Biological Chemistry 285–299, Harper and Row, New YorkGoogle 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, 477Google Scholar
- Whittaker, V. P. (1973). ‘Subcellular localization of neurotransmitters’, Adv. Cytopharmac., 1, 319–330Google Scholar
- Whittaker, V. P. (1974). ‘Molecular organization of the cholinergic vesicle’, Adv. Cytopharmac., 2, 311–317Google Scholar