Neurotransmitters

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Neurotransmitters
R.E.B, 4MedStudents.com, 2003

• Properties of neurotransmitters
• 1) synthesized in the presynaptic neuron
• 2) Localized to vesicles in the presynaptic
  neuron
• 3) Released from the presynaptic neuron under
• physiological conditions
• 4) Rabidly removed from the synaptic cleft by
  uptake or degradation
• 5) Presence of receptor on the post-synaptic
  neuron.
• 6) Binding to the receptor elicits a biological
  response

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Neurotransmitters found in the nervous system
EXCITATORY Acetylcholine Aspartate Dopamine Hi
stamine Norepinephrine Epinephrine Glutamate S
erotonin INHIBITORY GABA Glycine
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Acetylcholine synthesis

• In the cholinergic neurons acetylcholine is
  synthesized from choline. This reaction is
  activated by cholineacetyltransferase

As soon as acetylcholine is synthesized, it is
stored within synaptic vesicles.
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Release of acetylcholine from presynaptic neurons

• 1)When the nerve impulse (Action potential) moves
  down the presynaptic axon to the terminal bulb
  the change in the membrane action potential
  causes the opening of voltage gated calcium
  channels open allowing Ca2 ions to pass from the
  synaptic cleft into the axon bulb.
• 2)  Within the bulb the increase
• in Ca2 concentration causes the
• synaptic vesicles that contain
• acetylcholine to fuse with the
• axonal membrane and open
• spilling their contents into
• the synaptic cleft.

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Binding of acetylcholine to the postsynaptic
receptors

• The postsynaptic membrane of the receptor
  dendrite has specific cholinergic receptors
  toward which the neurotransmitter diffuses.
  Binding of acetylcholine trigger the opening of
  ion channels in the postsynaptic membrane
  initiating action potential that can pass in the
  next axon.

• Acetylcholine receptors
• Acetylcholine receptors are ion channels
  receptors made of many subunits arranged in the
  form (a2)(ß)(?)(d).
• When Acetylcholine is not 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 cell and
  efflux of K resulting in a depolarization of the
  postsynaptic neuron and the initiation of new
  action potential.

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Removal of Acetylcholine from the synaptic cleft

• In order to ready the synapse for another
  impulses
• 1)      The neurotransmitters, which are released
  from the synaptic vesicles, are hydrolyzed by
  enzyme present in the synaptic cleft
  Acetylcholinestrase giving choline, which
  poorly binds to acetylcholine receptors.
•  
• Acetylcholine H2O Choline H acetate
• 2)      The empty synaptic vesicles, which are
  returned to the axonal terminal bulb by
  endocytosis, must be filled with acetylecholine.

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Structure of AchE

• Acetylcholinesterase (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 molecule 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 system on the presynaptic
  membrane.

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Catecholamine Synthesis (Dopamine, Norepinephrine
and Epinephrine).

• 1) First Step Hydroxylation
• In this step the reaction involves the
  conversion of tyrosine, oxygen and
  tetrahydrobiopterin to dopa dihydrobiopterin.
  This reaction is catalyzed by the enzyme tyrosine
  hydroxylase. It is irreversible reaction.
• 2) Second step Decarboxylation
• In 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 reaction is the
  PLP (pyridoxal phosphate). In the nerve cells
  that secrete dopamine as neurotransmitter the
  pathway ends at this step.

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Catecholamine Synthesis (Dopamine, Norepinephrine
and Epinephrine).
3) Third step Hydroxylation This reaction is
catalyzed by the enzyme dopamine ß- hydroxylase.
The reactants include dopamine, O2 and ascorbate
(vitamin C). The products are 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 (ado-Met) form epinephrine
and S-adenosyl homocysteine (ado-Hcy).  
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Serotonin synthesis

• Serotonin is synthesized from the amino acid
  Tryptophan.
• The synthesis of serotonin involve two reactions
• 1)     1) Hydroxylation
• Tryptophan 5- Hydroxytryptophan
• The enzyme catalyzes this reaction is Tryptophan
  Hydroxylase.
• The Co- factor is Tetrahydrobiopterin, which
  converted in this reaction to Dihydrobiopterin.
• 2)      2) Decarboxylation
• 5- hydroxytryptophan Serotonin
• The enzyme is hydroxytryptophan decarboxylase.
• Serotonin is synthesized in CNS, Chromaffin
  cells.

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Break down of serotonin

• Serotonin is degraded in two recations
• 1) Oxidation
• 5-hydroxytryptoamine O2 H2O
  5- Hydroxyinodole-3-acetaldehyde
• 2) Dehydrogenation
• 5- Hydroxyinodole-3-acetaldehyde
  5-hydroxindole-3-acetate
• 
  (Anion of
  5-hydroxyindoleacetic acid)

• Aldehyde dehydrogenase 

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Other Neurotransmitters
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Summary