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) 6
6 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
Julius Axelrod (Nobel Laureate,1970) His discoveries concern the mechanisms which regulate the formation of norepinephrine in the nerve cells and the mechanisms which are involved in the inactivation of this important neurotransmitter. Synthesis of Catecholamines Tyrosine hydroxylase Phenylethanolamine- N-methyl transferase Dopa decarboxylase (L-amino acid 0\ (L-AAD decarboxylase) Adrenal medulla Dopamine B-hydroxylase Regulation of Norepinephrine Synthesis and Metabolism: Uak1 E 的 Post-synaptic Pre-synaptic Ca NENE ● Diffusion, Normetanephrine(NMN) metabolism 7
7 HO HO CH2 NHCH3 OH CH Epinephrine HO HO CH2 NH2 OH CH Norepinephrine HO HO CH2 NH2 CH2 Dopamine HO HO HC NH2 CH2 DOPA COOH HO HC NH2 CH2 Tyrosine COOH TH DD (L-AAD) PNMT DBH Adrenal medulla Synthesis of Catecholamines Tyrosine hydroxylase Dopa decarboxylase (L-amino acid decarboxylase) Dopamine β-hydroxylase PhenylethanolamineN-methyl transferase 1 3 Julius Axelrod (Nobel Laureate, 1970) His discoveries concern the mechanisms which regulate the formation of norepinephrine in the nerve cells and the mechanisms which are involved in the inactivation of this important neurotransmitter. Pre-synaptic Post-synaptic Ca2+ Na+ Tyrosine Cellular messengers and effects Diffusion, metabolism Tyrosine Dopa TH DD Dopamine (DA) NE DBH ATP Ca2+ NE DBH ATP NE NE COMT αR βR α2R NE (-) Signal Regulation of Norepinephrine Synthesis and Metabolism: Uptake-1 Normetanephrine (NMN)