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Acetylcholine

Acetylcholine. Eric Niederhoffer SIU-SOM. Synthesis and degradation Receptors Neuromuscular junction disorders. PDH complex (FAD, lipoamide, TPP). Pyruvate. Reuptake or diet. Acetylcholine. Acetate. + choline. Acetylcholine Synthesis and Degradation. Acetyl-CoA. + choline.

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Acetylcholine

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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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