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1、1Neurotransmitters nProperties of neurotransmitters:1) synthesized in the presynaptic neuron2) Localized to vesicles in the presynaptic neuron3) Released from the presynaptic neuron under physiological conditions4) Rabidly removed from the synaptic cleft by uptake or degradation5) Presence of recept
2、or on the post-synaptic neuron.6) Binding to the receptor elicits a biological response23Neurotransmitters found in the nervous systemEXCITATORYAcetylcholineAspartateDopamineHistamineNorepinephrineEpinephrineGlutamateSerotoninINHIBITORYGABA Glycine4Acetylcholine synthesis:nIn the cholinergic neurons
3、 acetylcholine is synthesized from choline. This reaction is activated by cholineacetyltransferase As soon as acetylcholine is synthesized, it is stored within synaptic vesicles. 5Release of acetylcholine from presynaptic neurons:n1)When the nerve impulse (Action potential) moves down the presynapti
4、c axon to the terminal bulb the change in the membrane action potential causes the opening of voltage gated calcium channels open allowing Ca+2 ions to pass from the synaptic cleft into the axon bulb.n2) Within the bulb the increase nin Ca+2 concentration causes the nsynaptic vesicles that contain n
5、acetylcholine to fuse with the naxonal membrane and open nspilling their contents into nthe synaptic cleft.6Binding of acetylcholine to the postsynaptic receptors:nThe postsynaptic membrane of the receptor dendrite has specific cholinergic receptors toward which the neurotransmitter diffuses. Bindin
6、g of acetylcholine trigger the opening of ion channels in the postsynaptic membrane initiating action potential that can pass in the next axon.nAcetylcholine receptors:n Acetylcholine receptors are ion channels receptors made of many subunits arranged in the form (2)()()(). When Acetylcholine is not
7、 bounded to the receptors, the bulky hydrophobic leu side close the central channels preventing the diffusion of any ions. Binding of two acetylcholine molecules to the receptors will rotate the subunits in which the smaller polar residues will line the ion channel causing the influx of Na+ into the
8、 cell and efflux of K+ resulting in a depolarization of the postsynaptic neuron and the initiation of new action potential.7Removal of Acetylcholine from the synaptic cleft:nIn order to ready the synapse for another impulses:n1) The neurotransmitters, which are released from the synaptic vesicles, a
9、re hydrolyzed by enzyme present in the synaptic cleft “Acetylcholinestrase” giving choline, which poorly binds to acetylcholine receptors.Acetylcholine + H2O Choline + H+ acetaten2) The empty synaptic vesicles, which are returned to the axonal terminal bulb by endocytosis, must be filled with acetyl
10、echoline.AcetylcholinestraseAcetylcholinestrase8Structure of AchEnAcetylcholinesterase (AchE) is an enzyme, which hydrolyses the neurotransmitter acetylcholine. The active site of AChE is made up of two subsites, both of which are critical to the breakdown of ACh. The anionic site serves to bind a m
11、olecule of ACh to the enzyme. Once the ACh is bound, the hydrolytic reaction occurs at a second region of the active site called the esteratic subsite. Here, the ester bond of ACh is broken, releasing acetate and choline. Choline is then immediately taken up again by the high affinity choline uptake
12、 system on the presynaptic membrane.9Catecholamine Synthesis (Dopamine, Norepinephrine and Epinephrine). n1) First Step: Hydroxylation: nIn this step: the reaction involves the conversion of tyrosine, oxygen and tetrahydrobiopterin to dopa & dihydrobiopterin. This reaction is catalyzed by the enzyme
13、 tyrosine hydroxylase. It is irreversible reaction. n2) Second step: Decarboxylation:nIn this step: the dopa decaboxylase will catalyze the decaoxylation of dopa to produce dopamine. The deficiency of this enzyme can cause Parkinsons disease. It is irreversible reaction. The cofactor in this reactio
14、n is the PLP (pyridoxal phosphate). In the nerve cells that secrete dopamine as neurotransmitter the pathway ends at this step. 103) Third step: Hydroxylation:This reaction is catalyzed by the enzyme dopamine - hydroxylase. The reactants include dopamine, O2 and ascorbate (vitamin C). The products a
15、re norepinephrine, water and dehydroascorbate. It is an irreversible reaction). The end product in noradrenergic cells is norepinephrine and the pathway ends her.4) Forth step: Methylation: This reaction is catalyzed by phenylethanolamine N- methyltransferase. Norepinephrine and S-adenosylmethionin
16、(ado -Met) form epinephrine and S-adenosyl homocysteine (ado-Hcy). Catecholamine Synthesis (Dopamine, Norepinephrine and Epinephrine). 1112Serotonin synthesis:Serotonin is synthesized from the amino acid Tryptophan.The synthesis of serotonin involve two reactions:1) 1) Hydroxylation:Tryptophan 5- HydroxytryptophanThe enzyme catalyzes this reaction is Tryptophan Hydroxylase. The Co- factor is Tetrahydrobiopteri
