Neurotransmitters are chemical messengers that transmit signals between neurons. They include acetylcholine, dopamine, serotonin, glutamate, GABA, and others. Neurotransmitters are synthesized and stored in neurons then released into the synaptic cleft in response to an action potential. They bind to receptors on the postsynaptic neuron and are then inactivated by reuptake or degradation to terminate their effects. Common neurological disorders involve imbalances in neurotransmitters, such as Parkinson's disease being linked to low dopamine levels and Myasthenia gravis involving antibodies against acetylcholine receptors.

1. Department of Biochemistry, KMC, DuwakotMonday, March
09, 2015
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NEUROTRANSMITTERS(For BDS I)
Rajesh Chaudhary

2. Communication within neurons is
“electrical”.
Communication between neurons is
“chemical”.
How neurons communicate?
Monday, March 09, 2015
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Rajesh Chaudhary

3. Neurotransmitters are the molecules that
act as chemical signals between nerve
cells.
Neurotransmitters
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Rajesh Chaudhary

4. Criteria for Neurotransmitters
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 1. Synthesis of molecule occur within the neurons.
 2. Storage of molecule occurs within the nerve ending prior to
release. E.g. in Synaptic vesicles.
 3. Release of molecule from presynaptic ending occurs in response
to an appropriate stimulus such as action potential.
 4. There is binding and recognition of the putative neurotransmitter
molecule on the postsynaptic target cell.
 5. Mechanism exists for the inactivation and termination of the
biological activity of the neurotransmitter.
Rajesh Chaudhary

5. Classification of Neurotransmitters
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Based on chemical composition
Group Examples
Amines Acetylcholine (Ach),
norepinephrine, epinephrine,
dopamine, 5-HT
Amino acids Glutamate, GABA
Purines ATP, adenosine
Gases Nitric oxide
Peptides Endorphins, tachykinins, many
othersRajesh Chaudhary

6. Neurotransmitters
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1. Acetylcholine (ACh) is involved in both learning and memory
and muscle movement.
2. Dopmaine impacts our arousal and mood states, thought
processes, and physical movement
3. Serotonin and norepinephrine are neurotransmitters involved
in levels of arousal and mood, and play a major role in mood
disorders such as depression
4. GABA is the main inhibitory neurotransmitter in the nervous
system; glutamate is the main excitatory neurotransmitter
5. Endorphins are a group of neurotransmitters that are involved
in pain perception and relief
Rajesh Chaudhary

7. Acetylcholine
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Acetylcholine (ACh) is involved in both learning and memory and muscle movement.
Monday, March 09, 2015Rajesh Chaudhary

8. Synaptic transmission
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 Neurotransmitters by presynaptic neuron  diffuse across
synaptic cleft  binds to a specific synaptic receptor 
activates  action.
 NOTE: All the process of neurotransmission is carried out
through ion channel and the potential generated by ions and
their concentration known as ACTION POTENTIAL.
Definition: The communication of one neuron to a target neuron through
SYNAPSE is called SYNAPTIC TRANSMISSION.
Rajesh Chaudhary

9. Synaptic transmission
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Rajesh Chaudhary

10. Neurotransmitter receptors
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 Classified according to the mode of action: 2
types.
1. Ionotropic (Example: Ligand-gated ion
channel)
2. Metabotropic (Example: G-protein coupled
receptor)
Rajesh Chaudhary

11. Neurotransmitter receptors
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Rajesh Chaudhary

12. Nicotinic acetylcholine receptor
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Nicotinic acetylcholine
receptor
Nicotinic ion-channel
receptor
Muscarinic receptor
Major classes of plasma membrane receptor
1. Ion-channel receptor
2. Hepta helical receptor
3. Receptors that are kinases or that binds
kinases Rajesh Chaudhary

13. Role of voltage-gated and ligand-gated
ion channels in neural transmission
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Rajesh Chaudhary

14. Regulation of neurotransmitters
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 Concentration of neurotransmitters may be
manipulated by:
 1. Changing the rate of synthesis
 2. Altering the rate of release at the synapse
 3. Blocking reuptake
 4. Blocking degradation
Rajesh Chaudhary

15. Monday, March 09, 2015
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Entry of L-DOPA in CNS DOPAMINE
Pyridoxal phosphate (Vitamin B6) required as cofactor
for this reaction.
Aromatic L-amino acid
decarboxylase /DOPA
decarboxylase
Rajesh Chaudhary

16. Biogenic amines
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 1. 3 catecholamines: dopamine, norepinephrine
(noradrenaline), and epinephrine (adrenaline)
 2. Histamine
 3. Serotonin
Difference between EPINEPHRINE and
NOREPINEPHRINE?
Why L-DOPA is used for the treatment of Parkinson’s disease?

17. Biogenic amines
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 Histamine: derived from the amino acid histidine, acts as
a neurotransmitter mediates in arousal and attention, as
well as a pro-inflammatory signal released from mast
cells in response to allergic reactions or tissue damage.
 Histamine is also an important stimulant of HCl secretion by
the stomach through histamine H2 receptors.
 Serotonin - a central nervous system neurotransmitter derived
from the amino acid tryptophan involved in regulating mood,
sleep, appetite, and sexuality.
Rajesh Chaudhary

18. The biosynthetic pathway for the
catecholamine neurotransmitters.
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Precursor for all three catecholamines
Rate limiting step Mitochondria
Cytoplasm
Vitamin C
Rajesh Chaudhary

19. The biosynthetic pathway for the
catecholamine neurotransmitters.
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Coenzyme necessary for
this step: S-adenosyl
methionine.
SAM is derived from?
Granules/
vesicles
Cytosol
Rajesh Chaudhary

20. Histamine and Serotonin
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NOTE: Key step is same for all cases: PLP-dependent decarboxylation!
PLP: Pyridoxal-phosphate, prosthetic group of
some enzymes, active form of vitamin B6.
Monday, March 09, 2015Rajesh Chaudhary

21. Histamine
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 Organic, nitrogen containing compound, regulates physiological functions, plays
role in immune response.
 Triggers inflammatory response.
 Produced by BASOPHILS and MAST CELLS.
 Easily dissolved in water and alcohol but not in ether.
 Synthesized by decarboxylation of histidine  catalyzed by histidine
decarboxylase.
 Hydrophilic amine.
Rajesh Chaudhary

22. Metabolism of Serotonin
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 Serotonine: derived from TRYPTOPHAN
 Activity is terminated by reuptake in
presynaptic neuron
 Primary route of degradation: oxidative
deamination.
Rajesh Chaudhary

23. Neuropsychiatric disorders
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1. Myasthenia gravis
2. Parkinson’s disease
3. Schizophrenia
Rajesh Chaudhary

24. Myasthenia gravis
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 Autoimmune disease
 Antibodies attack normal skeletal muscle tissue
 Can affect different muscle group in body
 Age: Can affect both young and adult
 Symptoms
 Double vision
 Droopy eyelids
 Easy muscular fatigue
 Breathing/swallowing difficulty
Other conditions associated with Myasthenia gravis
1. Thyroid disease
2. rheumatoid arthritis
3. Diabetes
4. thymoma in the chest cavity
Rajesh Chaudhary

25. Biochemical basis of Myasthenia gravis
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 Crux of Myasthenia gravis: 1. Congenital, 2. Autoimmune
disorder
 Treatment: Drug (Pyridostigmine bromide)  inhibition of
AchE increase half-life of Acetylcholine  concentration of
Acetylcholine increase  stimulation of AchR  more
signaling.
Rajesh Chaudhary

26. Treatment of Myasthenia gravis
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 Rarely cured, but symptoms can be improved.
 Mestinon, or pyridostigmine, is a cholinesterase
inhibitor which blocks the breakdown of
acetylcholine.
 Plasmapheresis: A procedure whereby the
offending antibodies are removed directly from the
bloodstream.
Rajesh Chaudhary

27. Organophosphorous poisoning
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 Inhibits acetylcholinesterase  accumulation of acetylcholine
 muscle overstimulation
 Chemicals chlorpyrifos and malathion  reproductive effects,
neurotoxicity, kidney/liver damage, and birth defects.
Acetylcholine accumulation at motor nerve overstimulation
of nicotinic expression  symptoms: muscle weakness, fatigue,
muscle cramps, and paralysis.
Rajesh Chaudhary

28. Organophosphorous poisoning
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Rajesh Chaudhary

29. 1. Medical Biochemistry, 4th. Edition by John W
Baynes.
2. Lehninger Principles of Biochemistry, 5th.
Edition by Nelson & Cox.
3. Harper’s Biochemistry, 25th. Edition
References
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1. Page no.: 450-454 & 878-882, Lehninger, 5th. edition. 2. Page no.: 639-641, Mark’s Basic
Medical Biochemistry, Old edition. Rajesh Chaudhary