Acetylcholine (ACh) is one of the first neurotransmitters to be discovered and Otto Loewi first described is as ‘vagus stuff’ as it is able to mimic the electrical stimulation of vagus nerve. Acetylcholine is produced by the enzyme choline acetyltransferase, using acetyl coenzyme A (acetyl CoA) and dietary choline as substrates. Acetylcholine and the interaction with its target have played a critical role in the basic concepts of neurochemistry. Chemical structure of acetylcholine is shown in Figure1A. Ach molecule can show torsion rotation around τ1, τ2 and τ3. Figure 1B and C indicate the energy configurations around τ2. According to nuclear magnetic resonance studies, gauche conformation is mostly dominant in medium.
Figure 1-Structure of acetylcholine
ACh is widely distributed in the nervous system. All vertebrates use ACh as motor transmission compound and it is the primary transmitter for peripheral ganglia. Furthermore, it mediates parasympathetic actions of autonomic nervous system and highly effective transmitter in the central nervous system.
Some species have evolved to block motor activity of their prey by releasing toxins. Some others from coral and plants use different blockage that is induced by cholinergic agents for protect themselves from predation. The high affinity and selectivity of these toxins enabled the type of ACh receptors to emerge as the first chemically characterized neurotransmitter receptor.
2. SYNTHESIS, STORAGE AND RELEASE OF ACETYLCHOLINE
The biosynthesis and storage of ACh can be divided into three processes that allow for recovery of hydrolyzed transmitter by choline transport back into the nerve ending, conversion by acetylation to active transmitter and then storage in a vesicle for subsequent release.
Figure 2 indicates the processes. The choline transport protein (ChT) functions at the nerve ending membrane to transport choline into the cytoplasm, where its
References: Albuquerque, E., Pereira, E., Alkondon, M., & Rogers, S. W. (2009, July 21). Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function. National Institute of Health , pp. 73-120. Brown, D. (2010). Muscarinic Acetylcholine Receptors (mAChRs) in Nervous System: Some Functions and Mechanisms. Journal of Molecular Neuroscience , 340-346. Crouse, A., & Hu, J. (2012). Structure and Dynamics of M3 muscarinic Acetylcholine Receptor. Nature , 552-556. Felder, C. (1995). Muscarinic Acetycholine Receptor: Signal transduction through multiple effector. The FASEB Journal , 619-625. Haga, K., & Kruse, A. C. (2012). Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature , 547-551. Ishii, M., & Kurachi, Y. (2006). Muscarinic Acetylcholine Receptors. Current Pharmaceutical Design , 3573-3581. Karlin, A. (2002). Emerging structure of the Nicotinic Acetylcholine receptors. Nature Rewievs of Neuroscience , 102-114. Kihara, T., & Shimohama, S. (2004). Alzheimer 's disease and acetylcholine. ACTA Neurobiology Experimentals , 99-105. Leach, K., Simms, J., Sexton, P., & Christopoulos, A. (2012). Structure–Function Studies of Muscarinic Acetycholine Receptors. Handbook of Experimental Pharmacology , 29-48. Siegel, G. (2006). Acetylcholine. In P. Taylor, & J. H. Brown, Basic Neurochemistry MOLECULAR, CELLULAR AND MEDICAL ASPECTS (pp. 185-211). Canada: Elsevier. SM, P., C, P., & IG., M. (1993). Acetylcholine transport, storage, and release. International revies of Neurobiology , 279-390. Stroud, R., & Finer-Moore, J. (1985). Acetylcholine Receptor Structure Function and Evolutiom. Annual revies on Cell Biology , 317-346. Webster, R., Maxwell, S., & Spearman, H. (2012). A novel congenital myasthenic syndrome due to decreased acetylcholine receptor ion-channel conductance. BRAIN A Journal of Neurology , 1070-1080.