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Understanding Acetylcholine: Synthesis, Degradation, and Receptors

Dive into the mechanism of acetylcholine synthesis, degradation, and its interaction with receptors. Explore neuromuscular junction disorders and the PDH complex. Learn about the various disorders associated with acetylcholine, acetylcholinesterase, and acetylcholine receptors.

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Understanding Acetylcholine: Synthesis, Degradation, and Receptors

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  1. Acetylcholine Eric Niederhoffer SIU-SOM • Synthesis and degradation • Receptors • Neuromuscular junction disorders

  2. PDH complex (FAD, lipoamide, TPP) Pyruvate Reuptake or diet Acetylcholine Acetate + choline Acetylcholine Synthesis and Degradation Acetyl-CoA + choline Choline acetyltransferase (CAT) (inhibited by mercurials) Acetylcholinesterase (AChE) (membrane associated; inhibited by nerve agents, sarin)

  3. Acetylcholine Receptor AChR a b ACh g (ore) ACh d a Miyazawa, A., Y. Fujiyoshi, and N. Unwin. 2003. Structure and gating mechanism of the acetylcholine receptor pore. Nature 423:949-955.

  4. Acetylcholine Receptor http://www.med.upenn.edu/ins/faculty/lindstro.htm Jon M. Lindstrom, Dept Neuroscience School of Medicine, University of Pennsylvania

  5. Neuromuscular Junction Disorders • Myasthenia Gravis autoimmune IgG against a1 subunit (muscle nAChR) • Inherited disorders with a, b, d, or e subunits (muscle nAChR) • Variety of disorders with neuronal nAChR • Kinetic problems with channels • IgG against M3 (mAChR) • AChE deficiency http://www.neuro.wustl.edu/neuromuscular/synmg.html

  6. Review Questions • How is ACh synthesized (substrates, enzyme, coenzyme)? • How is ACh degraded (products, enzyme, location)? • What are the composition and characteristics of AChR? • How does ACh interact with AChR (binding sites)? • What are the common disorders associated with ACh, AChE, and AChR?

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