Noradrenergic neurotransmission Flashcards
(31 cards)
What are the steps of Noradrenaline synthesis?
1) Tyrosin +MolcularO2+Fe+tertrahydrobiopterin —> DOPA +Dihydrobiopterin+H2O
Enzyme: tyrosine hydroxylase
2)DOPA +PLP —> Dopamine +CO2
Enzyme: DOPA decarboxylase
3)Dopamine +Ascorbate+O2 —> NE +H2O+Dehydroascorbate
Enzyme: dopamine B hydroxylase
( the things after the + are the products or co factors,see notes for good picture of the process)
Co-factors tyrosine -> DOPA
tetrahydrobiopterin -> dihydrobiopterin
Fe
O2
Co-factors Dopamine -> NE
Ascorbate -> dihydroascorbate
O2
Co-factor NE -> E
adoMet -> adoHcy
Reaction NE -> E
NE +SAM(adoMet) —> E +AdoHcy
Enzyme: phenylethanolamine N-methyltransferase
What is the rate limiting step of NE synthesis
step 1, tyrosine hydroxylase
- -feedback inhibition by NE
- by Ca
- phosphorylation by PKA,PKA and Ca/Calmodulin dep. kinase increases the affinity to the pterin cofactor
What do steroid hormones do for the conversion NE -> E?
They increase the activity of PNMT(phenylethanolamin N-methyltransferase )
What does MAO-A mainly break down? (monoamine oxidase)
Serotonin, Melationin, NE , E
What does MAO-B mainly break down (monoamine oxidase)
Phenethylamine, benzylamine
MAO-A inhibitors are used to treat parkinson, alzheimer disease.
What do MAO-A and MAO-B break down?
Dopamine, Tyramine, Tryptamine
Name a MAO-A inhibitor
Clorgilin
Name 2 MAO-B inhibitors
Deprenyl and Selegiline. Used in Parkinson and depression.
Describe VMTA2
VMTA2
vesicular membrane transporter 2
-12 transmembrane domain
-broad substrate-specificity to biogenic amines
(triptamine, tiramine,
amfetamin – compete with endogenous catecholamine)
-high affnity for reserpine irreversible inhibitor
– depletion of vesicles
What is the function of MAO
oxidative deamination of catecholamines
What is the function of COMT
methyl transfer to the 3-hydroxy group on the ring from S-adenosylmethionine
Describe the metabolism of NE in the brain
NE ( MAO ) —> DOPGAL (reductase) —– COMT —-> MHPG
MHPG ist he main metabolite in the brain, and can be used to determine the activity of the CNS noradrenergic transmission
What are the inhibitors of the re-uptake
Cocaine, SSRI’s , a-methyl-p-tyrosine ( comp. inhib of tryosine hydroxylase )
comp. inhib of tryosine hydroxylase?
a-methyl-p-tyrosine
What is the inhibitor of SR Ca ATPase?
Phospholambane
Where is B3 predominantly found and what happens when its stimulated?
Adipocytes. It leads to lipolysis in white adipocytes and non-shivering thermogenesis in brown fat
Where does NE innervate?
CNS and Autonomic nervous system Postganglionic sympathetic neurons -heart -intestinal smooth muscle -blood vessels -bronchi
Irreversible inhib. of VMTA2 (storage)
reserpine
Describe NE metabolism in peripheral neurons
MAO -> dehydrogenase -> COMT
B1 receptor acts where?
HEART :ionotropic and chronotropic effect,
GI : relaxation
