Question 23

Outline the production, release, and fate of noradrenaline at the sympathetic nerve terminal. 

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College Answer

The question consisted of three parts (production, release and fate of noradrenaline). The 
context was the sympathetic nerve terminal. The synthesis of Noradrenaline from Tyrosine was 
expected. Better answers mentioned the roles of Tyrosine Hydrolase, DOPA Decarboxylase and 
DOPA Beta-hydroxylase. Candidates were expected to describe the storage of Noradrenaline in 
vesicles and Ca++-mediated exocytosis in response to an action potential. Noradrenaline binds to 
post-synaptic and pre-synaptic receptors. Re-uptake, metabolism by MAO and COMT, and 
diffusion away from the synaptic cleft should have been discussed. An accurate diagram could 
be used to enhance the answer. 

Discussion

Production

  • Phenylalanine is transformed into tyrosine in the liver by phenylalanine hydroxylase, or it is ingested normally in the diet.
  • Tyrosine is converted by tyrosine hydroxylase into L-DOPA, and this is a rate-limiting step in the synthetic pathway.
  • L-DOPA (Levo-DihydrOxyPhenylAlanine) is transformed into dopamine by dopa decarboxylase, with vitamin B6 as a co-factor
  • Dopamine is then transformed into noradrenaline by dopamine-β-hydroxylase
  • Noradrenaline is N-methylated by phenylethanolamine N-methyltransferase in the chromaffin cells of the adrenal medulla to make adrenaline.
  • Noradrenaline is stored in presynaptic vesicles

Release

  • Depolarisation of the presynaptic membrane leads to calcium influx through voltage-gated N-type calcium channels
  • The calcium influx then activates the vesicle fusion proteins SNAP-25, syntaxin and synaptobrevin.
  • vesicles fuse with the presynaptioc membrane, and exocytosis results. 

Fate

  • Metabolised by MAO-A, MAO-B and COMT
  • Monoamine Oxidase (MAO)
    • Concentrated in the liver and kidney, but otherwise present all over the body
    • Present mainly in the outer mitochondrial surface
    • Present in sympathetic nerve terminals, and metabolises released neurotransmitter
  • Catechol -O- methyltransferase (COMT):
    • Concentrated in the liver and kidney, but otherwise present all over the body
    • Present mainly in the cytoplasm

References

Eisenhofer, Graeme, Irwin J. Kopin, and David S. Goldstein. "Catecholamine metabolism: a contemporary view with implications for physiology and medicine." Pharmacological reviews 56.3 (2004): 331-349.