Dr. Abraham S - Neurotransmitters

7/27/2019 Dr. Abraham S - Neurotransmitters

1/16

Neurotransmitters

Properties of neurotransmitters:

1) synthesized in the presynaptic neuron

2) Localized to vesicles in the presynaptic neuron

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

1

3) Released from the presynaptic neuron under

physiological conditions

4) Rapidly 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


2/16

2


3/16

Neurotransmitters found in the nervous system

EXCITATORY

Acetylcholine

Aspartate

3

DopamineHistamine

Norepinephrine

Epinephrine

Glutamate

Serotonin

INHIBITORY

GABAGlycine


4/16

Acetylcholine synthesis:

In the cholinergic neurons acetylcholine issynthesized from choline. This reaction is

activated b cholineacet ltransferase

4

As soon as acetylcholine is synthesized,

it is stored within synaptic vesicles.


5/16

Release of acetylcholine frompresynaptic 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 Ca+2 ions to pass

from the synaptic cleft into the axon bulb.

5

2) Within the bulb the increasein Ca+2 concentration causes the

synaptic vesicles that contain

acetylcholine to fuse with the

axonal membrane and openspilling their contents into

the synaptic cleft.


6/16

Binding of acetylcholine to thepostsynaptic receptors:

The postsynaptic membrane of the receptor dendrite has specific cholinergicreceptors 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.

Acet lcholine rece tors:

6

Acetylcholine receptors are ion channels receptors made ofmany subunits arranged in the form [(2)()()()].

When Acetylcholine is not bounded to the receptors, thebulky hydrophobic leu side close the central channelspreventing the diffusion of any ions.

Binding of two acetylcholine molecules to the receptors willrotate the subunits in which the smaller polar residues will linethe ion channel causing the influx of Na+ into the cell andefflux of K+ resulting in a depolarization of the postsynapticneuron and the initiation of new action potential.


7/16


8/16

Structure of AchE

Acetylcholinesterase (AchE) is an enzyme,

which hydrolyses the neurotransmitter

acetylcholine. The active site of AChE is

made up oftwo subsites, both of which are

8

cr t ca to t e rea own o . e

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 ofACh is broken, releasing acetate and

choline. Choline is then immediately taken

up again by the high affinity choline uptake

system on the presynaptic membrane.


9/16

Catecholamine Synthesis (Dopamine,Norepinephrine and Epinephrine).

1) First Step: Hydroxylation:In this step: the reaction involves the conversion oftyrosine, oxygen and

tetrahydrobiopterin to dopa & dihydrobiopterin. This reaction is

catalyzed by the enzyme tyrosine hydroxylase. It is irreversible reaction.

9

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.


10/16

3) Third step: Hydroxylation:

This reaction is catalyzed by the enzyme dopamine - hydroxylase.

The reactants include dopamine, O2 and ascorbate (vitamin C).

Catecholamine Synthesis (Dopamine,Norepinephrine and Epinephrine).

10

, .

is an irreversible reaction). The end product in noradrenergic cellsis 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).


11/16


12/16

Serotonin synthesis:

Serotonin is synthesized from the amino acid Tryptophan.

The synthesis of serotonin involve two reactions:

1) 1) Hydroxylation:

12

Tryptophan 5- HydroxytryptophanThe 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.


13/16

13


14/16

Break down of serotonin:

Serotonin is degraded in two reactions

1 Oxidation:1 Oxidation:

14

5555----hydroxytryptoamine + O2 + H2Ohydroxytryptoamine + O2 + H2Ohydroxytryptoamine + O2 + H2Ohydroxytryptoamine + O2 + H2O 5555---- HydroxyinodoleHydroxyinodoleHydroxyinodoleHydroxyinodole----3333----acetaldehydeacetaldehydeacetaldehydeacetaldehyde

2) Dehydrogenation2) Dehydrogenation5555---- HydroxyinodoleHydroxyinodoleHydroxyinodoleHydroxyinodole----3333----acetaldehydeacetaldehydeacetaldehydeacetaldehyde 5555----hydroxindolehydroxindolehydroxindolehydroxindole----3333----acetateacetateacetateacetate

(Anion of 5-hydroxyindoleacetic acid)

Aldehyde dehydrogenase


15/16

Other Neurotransmitters:

Neurotransmitter Derived fromDerived fromDerived fromDerived from EnzymeEnzymeEnzymeEnzyme

HistamineHistamineHistamineHistamine Histidine Histidine

15

GABAGABAGABAGABA

((((----AminoAminoAminoAmino

butyrate)butyrate)butyrate)butyrate)

Glutamate Glutamate

decarboxylase

Nitric OxideNitric OxideNitric OxideNitric Oxide Arginine Nitric Oxide

Synthase


16/16

NeurotransmitterMolecule

DerivedFrom

Site of Synthesis

Acetylcholine Choline CNS, parasympathetic nerves

Serotonin

5-Hydroxytryptamine (5-HT)

Tryptophan CNS, chromaffin cells of the gut, enteric

cells

GABA Glutamate CNS

Summary:

Histamine Histidine hypothalamus

Epinephrinesynthesis pathway

Tyrosine adrenal medulla, some CNS cells

Norpinephrine

synthesis pathway

Tyrosine CNS, sympathetic nerves

Dopaminesynthesis pathway

Tyrosine CNS

Nitric oxide, NO Arginine CNS, gastrointestinal tract

Documents

Dr. Abraham S - Neurotransmitters