Lecture 15 Flashcards Preview

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Flashcards in Lecture 15 Deck (19):
1

What is the first step (1/2) in catecholamine synthesis?

Tyrosine --> L-dopa
Enzyme = TH (tyrosine hydroxylase)
*Rate limiting step*
1. Tyrosine is taken up from circulation
2. Hydroxylation reaction
3. TH localized to nerve terminals

2

What is the second step (2/2) of catecholamine synthesis

L-dopa --> dopamine
Enzyme = DOPA decarboxylase
RAPID conversion - Ldopa doesn't exist for long

3

What extra step can be taken to make NE? Where does this reaction take place?

Dopamine --> NE
Enzyme = dopamine-B-hydroxylase
@ nor-adrengeric terminals
Happens INSIDE vesicles if it happens at all - not like cytosolic previous reactions

4

What product and enzyme are involved in end-product inhibition?

NE feeds back to TH via allosteric binding site

5

How does negative feedback inhibit TH?

Excess dopamine in the synapse is taken up into pre-synaptic side via AUTORECEPTOR

6

What are the 2 mechanisms by which catecholamine NT turnover is regulated?

MAO = monamine oxidase
- Amine --> aldehyde
COMT = catecholamine O methyl transferase
- Adds methyl group

7

What is the mechanism for inactivating a synpase?

Catecholamine reuptake via DA transporter
Na cotransport

8

If removed, which of the following will prolong the action of catecholamines in the synapse: MOA, COMT, or DA transporter?

DA transporter!
Key differentiation point

9

What is the difference between DAT and NET transporters?

BOTH remove dopamine, E and NE
Differ via effective inhibitors
DAT - used to treat ADHD
NET - used to treat depression

10

What molecule is a good marker in CSF for dopamine? Which disease has low level of this molecule?

HVA = homovanillic acid
↓ in Parkinson's
Signals basal ganglia disorder

11

What molecule is a good marker for NE? Where is this measured: central vs peripheral?

VMA = vanillymandelic acid
NE @ periphery
Diagnostic for pheochromocytoma (adrenal gland tumor)

12

Describe adrenergic receptors.

Alpha or beta
7 transmembrane domains
Activate G protein

13

Where are DA 1 vs DA2 receptors?

DA2: cortico-striatium afferents
DA1: striatum interneurons
(Remember striatum = caudate nucleus + putamen)

14

What are the 2 classes of dopamine receptors? Describe important features.

D1 vs D2
D1: effected by cAMP, NOT in pituitary
D2: at the pituitary - these are the ones that play a role in prolactin release

15

Where are dopamine NTs bound in the brain?

Localized: striatum & substantia nigra
Neuronal pathway:
- Cell body @ SN
- Goes to striatum & frontal cortex

16

Describe the nigro-striatal pathway. What disease is related?

DOPAMINE pathway
Cell bodies @ substantia nigra
To striatum
Fxn = connect basal ganglia = coordination of motor movement
Degenerates in Parkinson's

17

Describe the meso-limbic pathway.

DOPAMINE pathway
Cell bodies @ substantia nigra
To median forebrain bundle, etc, etc

18

Is NE localized or diffuse? Where is the origin?

Diffuse
Projects out of locus coeruleus

19

Describe what you know about Parkinson's from this lecture.

Loose dopamine path in basal ganglia = Nigro-striatal pathway
Start @ substantia nigra
End @ striatum
Connects basal ganglia to coordinate motor movements
Low HVA