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SDLS 2008 Biosynthesis of Neurotransmitters

SDLS 2008 Biosynthesis of Neurotransmitters

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Published by: Johanna Estanislao on Aug 25, 2012
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01/16/2013

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Detoxicol
SDLS 2008
Medicine for the intoxicated
 
File Created on 01/23/2005 10:08 AM
Topic:
Biosynthesis of Neurotransmitters
Transcriber(s):
JC, Shiela, Joanne
Lecturer:
Professor Patricia Generoso
Editors:
JC Tayco, Mark Lomboy, Pre Ausan, Erika Mendoza
No. of pages: 5SYNTHESIS OF NEUROTRANSMITTERSOverviewA. NeurotransmittersB. Overview of Synapse
Synaptic cleft
Summary of Synapse
C. CNS function
External stimuli
CNS
Glial cells
Blood-brain Barrier 
How the neurons interact?
Pre-synaptic axon terminal
Myelination of neuron
D. Kinds of Neurotransmitters
Major classification1.Excitatory2.Inhibitory
Serotonin
 Acetylcholine
o
Cholinergic receptors
Snake toxinsGlycine
GABA
Catecholamines
o
Formation of Dopa
o
Dopamine
Formation of Dopamine
o
Epinephrine
Formation of epinephrine and norepinephrine
Movement of electrical impulse
o
Depolarization of the neuron
o
Hyperpolarization
o
Clinical CorrelationWhat happens to the drug addicts?
Histamine
Melatonin
How is serotonin, dopamine,epinephrine and norepinephrin degraded?
Clinical Application
E. Neuropeptides
Some men are faithful, some are not?
F. Long and short-term memory
What is biochemical pathway for long term memory?
Neurotransmitters
:
Involved in:
o
emotions, thirst, hunger, pleasure, sex, memoryformation
synthesized from food you eat
from amino acids*the more complex neuropeptides are synthesized fromamino acids (undergo the same normal synthesis as anordinary protein synthesis, but this time, it is synthesized inthe brain)*In the brain it is involved in communication of neurons withinthe cellConclusion: The CNS makes sure there is ongoingcommunication.100 billion – 10 trillion neurons inside the cell.controlled by the food that you eat*
Nota Bene (NB):
neurons cannot regenerate*brain does not rest*neurotransmitters need = 4 us to sleep
Overview of Synapse(Communication of one cell toanother):Components for Synapse to occur:
1. mitochondria2. pre-synaptic cell3. post-synaptic cell4. synaptic cleft*neurotransmitters’ site: vesicles*electrical impulse: initiate & stimulate the release of neurotransmitters by:presynaptic cellpresynaptic membraneexocytosisreleased of neurotransmitters
Synaptic cleft (gap):
between pre- & post – synapse
20 Armstrong (2 nm) can bebridged by electrical impulse moving along theneurons
200 Armstrong (20 nm) cannot bebridged by electrical impluse the gap
Use neurotransmitters
(NB):
Movement or impulse in the nerve (electrical→chemical →electrical)ave. neuron = 1 m. in length*small neuron = 1 mm ATP > biggest user of this is CNS* (103 g ATP/day)
Summary of Synapse
*Between the synaptic neurons is a tiny gap called thesynaptic cleft. However small the electrical signal is a nervecarrying a message to or from the CNS,
cannot bridge
thesynaptic cleft as it is.
 
*Instead, it triggers a process that will send the vesiclescontaining transmitters molecules towards the membrane of the pre-synaptic cell.*When reaching the pre-synaptic membrane, the vesicles willfuse with it and spill out the transmitter.*The transmitter molecules bind to receptor molecules on thepre-synaptic membrane and the receptors.*Respond by generating a new electrical impulse in the post-synaptic cell.*So, by converting the electrical impulse the chemicalimpulse and back, the message reaches the next neuron.Some of the transmitter molecules will be brought back byreuptake pumps and “recycled”.
NB:
If you have a big exam the next day, do not eat a lot of carbohydrates because it will make you sleepy but with ahappy feeling, because you suddenly gave the brain glucosethat it needs. According to Prof. Generoso, with highconcentration of glucose it is like a high way in signaling of neurons.
Moral lesson:
Eat less carbohydrates but eat more proteins. After eating a lot of proteins dilute it with a lot of water (water therapy) to prevent arthritis and gout.
NB:
If you eat a diet high in protein, it makes you more alert. According to Prof. Generoso it makes your neuron signalingstuck in traffic.*Brain has to be constantly supplied by ATP:- Mitochondria = energy provider 
CNS function:
response to external stimuli
communicate information fromoutside to inside
controls the entire person-
Epinephrine
– “fight or flight”Effects:- BP ↑- pump more blood to the brain, muscles(results: enough energy)
- External stimuli:Skin:
touchpainheatcold
Eye
intensitylightshapecolar position
Tongue
acidbitter saltalkaline
Nose
fragrance
Ear 
Pitch quality*different senses are stimulated and all are connected toyour nerves*2.4% = nervous tissue of adult weight*83% of this = brain*103 g glucose/day = brain consumesbrain 
CNS
neuronsglial cells
NB:
glial cells > neurons*adult brain: 100 billion 10 trillion neurons
Glial cells:
Schwann cells
oligodendrocytes
microglial cells
ependymal cells
astrocytes
Blood-brain Barrier 
o
collection of astrocytes
o
collection of capillaries
o
Function: chemicals thatare soluble in H20 will not be able to bridge thru theblood-brain barrier 
Conclusion:
brain is protected from entry of it about anychemical.
How the neurons interact?
Electrical impulse
membrane depolarization
ions: Na, K membrane depolarization of nerves
 ATP-ase
Chemical impulsePre-synaptic axon terminal:
 
site of chemicalneurotransmitters
chemicalneurotransmitters are synthesized from:
cytosol
near synapse
neuron
Synthesized fromsimple AA but hormones that are normallyfound isolated in different organs,(vasopressin, oxytocin, GnH) discoveredalso in brain.
o
They are called“neuropeptides” and the brainsynthesizes them Pain threshold = high enkephalin level, endorphins.↑Enzymes (synthesis) site – pre-synaptic neurons
Released upon stimulation
Neurotransmitters
 – found vesicles (inside pre-synaptic neuron)
Myelination of neuron
important for impulse of electrical impulse (not chemical)
neurotransmitters
– move along synapse
Kinds of Neurotransmitters:Major classification:Excitatory:
causes depolarization of post-synaptic celltherefore it is impulse propagation
2
 
 Acetylcholine (Ach)
Dopamine
Epinephrine
Noropinephrine
Serotonin
Melatonin
Histamine
Glutamate (E)
 Aspartate (D)
Inhibitory:
GABA (Gamma Amino Butyric Acid)
Glycine < G >
Taurine
Serotonin:
synthesized from Tryptophan (W)
Vasoconstrictor 
In the brain, it gives happy feeling
Tryptophan forms SerotoninTryptophan
hydroxylation5-hydroxytryptophan 
tyrosine hydroxylaseSerotonin
decarboxylation processacted upon by Tryptophan hydrolaseto give you 5 – hydroxytryptophan
acoenzyme: BH4/tetrahydrobiopterin + 0
2
Tryptophan metabolites are excreted in urine and feces
Tryptophan
Forms additional indole derivatives
Decarboxylation of tryptophan to tryptamine
Oxidation forms indole-3-acetate
Prinicipal normal urinary catabolites
5-hydroxyindoleacetate
indole-3-acetate
Acetylcholine:
 Acetyl CoA →Choline →Acetylcholine
NB:
Neurotransmitters are released, not supposed to remainbound to its receptors post-synaptic neuron (memb.), after binding with receptor:
acetylcholine esterase (cleaves it)
as a result end up forming AcetylCoAacetyl coa + choline = go back d pump>goes back as acetyl coa & choline to the vesicles (storage& synthesized to form Acetylcholine)
Cholinergic receptors
receptors specific for Ach
2 types:
nicotine
muscarin
toxins that ineract with it
(inhibit Ach esterase/Ach
transferase)
cobra toxins
bonggaro toxins
succi toxins – present in “red tides”
Snake toxins:
inhibit Ach transferase, cholinergic receptorsor Ach esteraseNa – K pumpNa-Ca pump = nerves*release of Ach = release of Ca*action potential (pre-synaptic neuron)
allow Ca to enter and stimulateexocytosis of neurotransmitters, and then Ach isreleased (vesicle).*post-synaptic neuron
cyclic AMP, Protein kinase (bothare involved in electrical impulse)after the neurotransmitters are released, there is “reuptake”*post-synapse neuron (excitary neurotransmitter)
depolarization happens thatcauses continuous electrical impulse transmission
Glycine
inhibitory
do not take too much because itwould cause neurologic symtoms
predominant inhibition in spineand Brain stem
 Action inhibited by Strychnine (acton glycine receptor) but glycine and Strychnine arevery different in structure.
Participates in biosynthesis of 
Glycine conjugates
many metabolites and pharmaceuticalsare excreted as water-soluble glycineconjugates
glycocolic acid
hippuric acid
Creatine
sarcosine (N-methylglycine) derived fromglycine and S-adenosylmethionine
Heme
nitrogen and
α
-carbon of glycinecontribute the nitrogen and both an
α
-carbonof the pyrrole rings and methylene bridgecarbons of heme
Purines
entire glycine molecule becomes atoms 4,5, and 7 of purines
GABA:
From Glutamate (E)
decarboxylation @ alpha carbon
Inhibited by diazepam
Formation and catabolism
γ 
-aminobutyrate(GABA)
Formed by decarboxylation of L-glutamate(catalyzed by L-glutamate decarboxylase)
Convert putrescine to GABA, either bydeamination by diamine oxidase or via N-acetylateintermediates
Catabolism:GABA 
GABA transaminasesuccinate semialdehydeL-lactate dehydrogenase
γ 
-hydroxybutyrate
3

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