Synthesis,storage and release of acetylcholine: Na' 0斯 Choline Synaptic Ao-CaA ChAT Ach Antiporter Pre-synaptic cell CAT choline acetyltransferase AchE Post-synaptic AchE acetylcholinesterase cell Degradation of acetylcholine: HO 0 Choline Acetic acid (CH),N-CH,-CH,-O-C-CHa AchE (CHj)3 N+-CHz-CHz-OH+CHaCOOH AchE Trp-86 600.000 Ach molecules/AchE min Ser-203 tumnover time of 150 microseconds Steps involved in the action of acetylcholinesterase: 1.Binding of substrate(Ach) 2.Formation of a transient intermediate (involving-OH on Serine 203,etc.) 3.Loss of choline and formation of acetylated enzyme 4.Deacylation of AchE(regeneration of enzyme) 66 Synthesis, storage and release of acetylcholine: Pre-synaptic cell Post-synaptic cell Ach Ca2+ Na+ Choline (10 µM) Choline Recognition by receptors Ca2+ Ach Ach Ach Nerve impulse NN NM Ach Ac-CoA ChAT Ach AchE AchE choline + acetic acid CAT = choline acetyltransferase AchE = acetylcholinesterase Synaptic cleft Antiporter + CH3COOH AchE (CH3)3 N+–CH2–CH2 (CH3)3 N+–CH2–CH2–O–C–CH3 –OH O H2O (-) (H) AchE Trp-86 Glu-334 His-447 Ser-203 Degradation of acetylcholine: Steps involved in the action of acetylcholinesterase: 1. Binding of substrate (Ach) 2. Formation of a transient intermediate (involving -OH on Serine 203, etc.) 3. Loss of choline and formation of acetylated enzyme 4. Deacylation of AchE (regeneration of enzyme) 600,000 Ach molecules / AchE / min = turnover time of 150 microseconds Choline Acetic acid