Chemical And Biochemical Basis Of Neurotransmission Flashcards
5 steps of chemical communication
1) Signal produced and released
2) signal is received
3) signal transmission and amplification occurs
4) cellular response occurs in target
5) signal termination
- occurs at any of the previous 4 steps
Which are classical neurotransmitters?
Acetylcholine
Amino acids (note: these DONT cross BBB)
- glutamate
- aspartate
- GABA
- Glycine
Amines
- catecholamines
- serotonin
- histamine
all are small molecules
What are non classical neurotransmitters?
Opioids (neuropeptides)
Tachyknins (neuropeptides
Nitric oxide
Lipids
How are amino acids used?
1) generate body proteins
2) generate Nitrogen containing compounds
- hormones
- purines
- Pyrimidines
3) broken down to urea and excreted
4) catabolism by other metabolic processes
The BBB transport mechanisms
1) Simple diffusion
- water
- oxygen
- CO2
- non-polar drugs
2) facilitated diffusion vis specific transporters
- glucose (via GLT-1 (endothelial cells) or GLT-3 (neurons))
- essential FA’s only
- monocarboxylic acids (lactate, acetate, pyruvate, ketones)
- large neutral AAs
- vitamins
3) receptor-mediated
- insulin
- transferrin
- IGFs
Specific characteristics of the BBB
1) possess very tight junctions between endothelial cells
2) narrow intercellular spaces
3) lack pinocytosis in cells
4) continuous basement membrane
5I) astrocytes extension
How are large neutral AAs transported into the BBB and what AAs does this constitute?
Phe, Leu, Tyr, lle, Val, Trp, Met, His
Use the L-system AA transporter to get above AAs in and out of the BBB
5 steps of chemical neurotransmission
1) Synthesis of the neurotransmitter in the presynaptic neuron
2) Storage in presynaptic nerve terminal
3) release of the neurotransmitter into synaptic cleft
4) binding and recognition of neurotransmitter by receptors
5) termination of the action
Steps of synaptic neurotransmission
1) action potential depolarizers presynaptic terminal membrane and Ca2+ rushes into the synaptic terminal
2) Ca2+ ions in terminal promote fusion of vesicular and terminal membranes, allowing neurotransmitters to release into synaptic cleft
3) neurotransmitter binds with receptor on channels across synaptic cleft and opens, allowing Na+ to rush into post synaptic neuron and excite it.
* cycle 1-3 is repeated until target organ is reached*
What enzymes generate acetylcholine and catabolism it
Generate = choline acetyltransferase (ChAT)
Catabolism = Acetylcholinesterase (AChE)
acetyl CoA (glucose byproduct) + choline (essential protein) -> acetylcholine
How is AChE inhibited?
1) Military nerve gases (sarin/tabun/soman)
2) Green mamba snake venom
3) Donepezil (aricept) medications
How are glycine, GABA, glutamine and aspartate all produced
Glycine
- serine -> glycine via folate enzyme
Aspartate
- Oxaloacetate -> Aspartate via aminotransferase/ pyridoxal phosphate (PLP) enzyme
Glutamate
- A-ketoglutarate -> glutamate via aminotransferase/ PLP anime
GABA
- Glutamate -> y- aminobutyric acid (GABA)
How is PLP dervived?
From vitamin B6 and enzymes that require zinc to synthesis
- deficiencies in either of these vitamins can lower the generation of PLP and consequently aspartate/glutamate/GABA
Clinical correlates assocaited with GABA
Huntington’s
Parkinson’s
- insufficient dopamine-producing cells
Senile dementia
Alzheimer’s
Schizophrenia
Epileptic seizures
- treated with Valproic acid since it inhibits GABA transaminase and causes increase GABA production
CLincial correlates associated with aspartate and glutamate
Excitotoxicity
- leads to neuron death
ALS
Alzheimer’s
