Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology GPP > NORADRENALINE: SYNTHESIS, STORAGE, RELEASE, FATE & METABOLISM > Flashcards

NORADRENALINE: SYNTHESIS, STORAGE, RELEASE, FATE & METABOLISM Flashcards

(104 cards)

Start Studying
1
Q

How is cholesterol produced in the adrenal cortex

A

• Cholesterol-processing enzymes in sER, inner mitochondria membrane
– Tubulovesicular mitochondria.
• Much inner membrane surface area
• MuchP450s
• Parenchymal cells can produce cholesterol de novo
– Mainly endocytosis of LDL
– Cholesterol-rich lipid droplets in cytoplasm
• Capsule + 3 cell layers
11

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What cells of the adrenal cortex can produce cholesterol de novo

A

Parenchymal cells can produce cholesterol de novo
– Mainly endocytosis of LDL
– Cholesterol-rich lipid droplets in cytoplasm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What’s the adrenal cortex made of

A

Capsule + 3 cell layers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What part of the adrenal half is a modified sympathetic ganglion

A

Adrenal medulla

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Function of adrenal medulla

A

– Release catecholamines to ECF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the cells of the adrenal medulla

A

They’re called pheochromocytes
– Axonless secretory cells
– Two cell subpopulations
• Same cell population under different physiologic states – Concent cortisol exposure
• Norepinephrine (noradrenaline) producing cells
• Epinephrine (adrenaline) producing cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do pheochromocytes exceed their cells to the ECF

A

Secrete products from granulesECF by exocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Does the adrenal medulla contain post ganglionic fiber

A

• Adrenal medulla is a modified part of sympathetic nervous system
– Modified sympathetic ganglion that does not give rise to postganglionic fibers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What stimulates the release of the medullary hormones into the circulation

A

– Stimulation of preganglionic fiber prompts secretion of hormones into blood
•About. 20% of hormone release is norepinephrine
•About 80% of hormone released is epinephrine(adrenaline)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the similarities between a normal sympathetic ganglion and an adrenal medulla

A

In a normal sympathetic ganglion, at the pre synaptic cleft, Ach is produce and the. At the post ganglionic cleft, Epinephrine and norepinephrine are produced

But In the adrenal medulla, the presynaptic ganglion brings Ach into the medulla where Epinephrine and norepinephrine are produced, in the absence of moving to a post synaptic cleft, the catecholamimes are secreted into the ECF directly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What’s the primary stimulus for increased adrenomedullary secretion

A

Stress

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Epinephrine and norepinephrine are released into the ECF by exocytosis of what granules

A

– Secreted into blood by exocytosis of chromaffin granules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the functions of epinephrine

A

– Maintenance of arterial blood pressure
– Increases blood glucose and blood fatty acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What’s the stimulus for Epinephrine secretion

A

Stress (psychological reactions), elevated sound levels, intense light, low blood sugar levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the synthesis of epinephrine

A

Tyrosine
|Tyrosine hydroxylase
|
DOPA
|DOPA decarboxylase
|
Dopamine
|Dopamine B hydroxylase
|
NE
|PNMT
|
Epinephrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Conc of L-dopa in the plasma

A

1-1.5 mg/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How is L- Dopa transferred into cells

A

Active transport into cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How many enzymes convert L-Dooa into epinephrine

A

4 enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What’s the plasma ratio of norepinephrine to epinephrine

A

ratio 8:2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Explain the conversion of tyrosine to adrenaline

A

Phenylalanine
| phenylalanine hydroxylase
|
Tyrosine
|tyrosine hydroxylase
|
L Dopa
|Dopa decarboxylase
|
Dopamine
|Dopamine B hydroxylase
|
Norepinephrine
|phenylethanolamine N methyltransferase
|
Epinephrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

I’m what step of the synthesis of epinephrine is tetrahydrobiopterin (O2) converted to dihydobiopterin (H2O)

A

Tyrosine to L Dopa (tyrosine hydroxylase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

In what step in the synthesis of epinephrine is S-adenosylhomocystein converted to S-adenosylmethione

A

Norepinephrine to epinephrine (phenylethanolamine N methyl transferase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What’s the % to which catecholamines are produced

A

Epinephrine 80%
Norepinephrine 20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the adrenergic receptors

A

• α1β1: excitatory
• α2β2: inhibitory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What’s the location of the alpha 1 receptor
Most synaptic target cells
26
What’s the location of the alpha 2 receptor
Digestive system
27
What’s the location of the beta 1 receptor
Heart
28
What’s the location of the beta 2 receptor
Skeletal muscle Smooth muscle of some blood vessels Organs
29
What has more affinity for alpha 1 receptor
NE
30
What has more affinity for alpha 2 receptor
NE
31
What has more affinity for beta 1 receptor
NE and Epinephrine
32
What has more affinity for beta 2 receptor
Epinephrine
33
What type of response is elicited from the alpha 1 receptor
Generalised arteriolar constriction
34
What type of action is elicited by the alpha 2 receptor
Decreased motility of the digestive tract
35
Hat kind of action is elicited by the beta 1 receptor
Increased rate and strength of cardiac cells
36
What kind of action is elicited by the Beta 2 receptor
Breakdown of glycogen in skeletal muscle Bronchioles dilation and arteriolar vasodilation in skeletal muscle and heart (Decreased smooth muscle constriction)
37
What’s the function of tyrosine hydroxylase
Ring hydroxylation to L-DOPA (L-Dihydroxy-PhenylAlanine)
38
What cofactor does tyrosine hydroxylase contain
Contains Fe2+; tetrahydrobiopterin cofactor
39
What regulates tyrosine hydroxylase
Activity regulated by preganglionic nerves – Get phosph’n PKA, PKC and calmodulin-dependent kinases
40
What’s the long term stimulation of tyrosine hydroxylase
upregulation of transcription, translation
41
What inhibits the production of tyrosine hydroxylase
Increased L-DOPA
42
What’s another name for Dopa decarboxylase
L-aromatic amino acid decarboxylase
43
What’s the go factor for DOPA decarboxylase
Pyridoxal phosphate cofactor
44
Where is The DOPA decarboxylase end product found
In the CNS
45
Where is DOPA decarboxylase stored and how is it released
• Stored in secretory vesicles – Enter by active transport – MVATs (Vesicular MonoAmine Transporters)
46
What provides the side chain hydroxylation to become noradrenaline
3) Dopamine beta Hydroxylase
47
What cofactors do dopamine beta hydroxylase contain
Contains Cu; Vit C cofactor
48
Where does the reaction of dopamine bet hydroxylase occur
• Rxn w/in secretory vesicle
49
Where does the action of dopamine beta hydroxylase take place
• Rxn w/in secretory vesicle
50
Where is the end product of dopamine beta hydroxylase
• End prod in symp. nerves, most central catecholaminergic neural tracts
51
What’s the function of Phenylethanolamine N- MethylTransferase (PNMT
N-methylation to epinephrine
52
What’s the S donor for phenylethanolamine N methyl transferase
S- Adenosylmethionine
53
Where does the action of phylehanolamine N methyl transferase occur
Cytoplasm
54
What happens to norepinephrine and epinephrine after the action of phenylethanolamine n methyl transferase
– Norepinephrine leaves vesicle • Passive transport • Concent gradient – Epinephrine must reenter secretory vesicle • Active transport
55
What does the expression of PNMT depend on
• Expression depends on high local cortisol – From adrenal cortex – Through sinusoid system
56
Explain Transcriptional activation of PNMT
Transcriptional activation of PNMT gene through ligand-activated glucocorticoid receptor – Also other transcription factors
57
What stimulates PMNT
Glucocorticoids
58
What’s the effect of adrenaline on PMNT
Feedback inhibition
59
What other places can PMNT be found
Other than adrenal medulla kidney, lung, pancreas
60
Function on non specific NMT
Contributes to peripheral conversion norepi. to epi.
61
Where are cathecolamine stored
Secretory vesicles
62
How are cathecholamines transported
Active transport via VMATs – ATP-driven proton pump – In vesicle membranes – pH, electrical gradient – Antiporte
63
What are the 12 transmembrane helical segments found in secretory vesicles
Related to plasma membrane monoamine transporters
64
How are Ach released from presynaptic ganglion
Nicotinic receptors Get depolarization of pheochromocytes act’n voltage-gated Ca2+ channels influx Ca2+ exocytosis of secretory vesicles • Chromogranins, DBH, ATP, other peptides released
65
What other things are realeased at the presynaptic vesicle along with Ach
Chromogranins, DBH, ATP, other peptides released
66
What can cathecolamine not penetrate
• BBB • Fetus
67
How does fetus get catecholamines
Fetal production (mostly norepi) through fetal zone • Impt in intrauterine life (cardiovascular responses) • Large • Placenta expresses catecholamine degrading enzymes
68
What catecholamine is more in featal life
NE
69
How does NE get degraded I’m featal life
Placental norepi. transporter – Delivers circulating fetal catechol’s for degrad’n
70
What’s the half life of catecholamines
• Short-lived molecules – 10 sec to 1.7 min
71
What are most catecholamines associated with
• 50-60% associated with albumin
72
How are catecholamines eliminated
– **At synapse, ISF near sympathetic neurons** • Reuptake into nerve terminals • Reenter vesicles via VMAT OR • Become degraded by monoamine oxidase (MAO, MAOIs bind to MAO for inhibition) – **In target cells** • Degraded by Catechol-O-MethylTransferase (COMT) – **5% directly filtered into urine**
73
When epinephrine is acted upon by COMT, what does it become
(At the target site) It becomes metanephrine Then becomes metanephrine sulfate or glucoronide
74
Where does MAO degrade catecholamine
At the synapse
75
Where does COMT degrade catecholamine
At the target site
76
When MAO acts of epinephrine, what does it become
(At the synapse) 3,4 dihydroxy mandelic acid
77
How is 3,4 dihydroxymandelic acid degraded
Acted on by COMT to give 3, methoxy 4, hydroxymadelic acid **aka vanillymandelic acid**
78
How else can 3, methoxy 4, hydroxy mandelic acid (vanillymandelic acid) be gotten other than degradation of 3,4 dihydroxymandelic acid ( by COMT)
By degradation of metanephrine by MAO
79
How do you remember the break down of epinephrine and where each enzyme works on
On a straight line(vertically) it’s worked on by COMT (at target site) So from epinephrine to metanephrine And from 3,4 dihydroxymandelic acid to 3,methoxy 4, hydroxylase mandelic acid Are both by COMT By on a horizontal line, it’s by MAO (at synapse) So from epinephrine to 3,4 dihydroxymandelic acid And from metanephrine to 3, methyl 4 hydroxymandelic acid Are both by MAO
80
Where is MAO found
Outer mitochondrial membrane
81
What are the substrates of MAO
also include serotonin, histamine
82
How does MAO work
Oxidizes amino grp to aldehydes – Further oxidation by nonspecific aldehyde dehydrogenase
83
What is the ultimate product of MAO
Ultimate production of dihydroxymandelic acid (DOMA)
84
What are the types of MAO
– MAO-A and MAO-B
85
What kind of degradation does COMT do
extraneuronal degradation
86
What is the methyl donor for COMT
S-Adenosyl methionine
87
What kind of catecholamine is COMT important for degrading
Important to circulating catecholamines
88
How does catecholamine get its final conjunction
Sulfate, glucuronate in liver, gut – Excretion through urine
89
What are the sympathoadrenal functions
**1) Catecholamines regulate intermediary metabolism.** - Carbohydrate metabolism (β-AR ): blood glucose levels increased - Fat metabolism (β-AR ): activates a hormone-sensitive lipase, triglyceride lipasemetabolizes fats into fatty acids (FFAs) and glycerol - Protein metabolism (β-AR ): decreases the release of amino acids from skeletal muscle **2) The sympathetic nervous system regulates thermogenesis**. - Shivering thermogenesis: - Nonshivering (chemical) thermogenesis: brown adipose tissue in the rat **3) Adrenergic receptors mediate cardiovascular responses to stress** (β-AR ) **4) physiologic implications**
90
What are the physiological implications of the sympathoadrenal catecholamines
**• General: activates fight/flight mechanisms.** – Mobilizes energy, redist’s blood **• Opposes parasympathetic system** – Promotes digestion, storage of energy – BUT distinct target cell pop’ns w/in organs **• Many targets; overall** – Increase cardiac output, blood pressure – Bronchodilationmatched perfusion w/ increased ventilation – Blood diverted from viscera and skin to muscle **• Retain blood to brain** – Mobilize fuel from energy stores
91
Is PNMT Involved in the synthesis of NE
No
92
Where is PNMT found
Adrenal medulla
93
How is NE stored
In vesicles carried by VMAT
94
What synthesis of Epinephrine occurs before entry into the vesicles
Tyrosine - - - - -> Dopamine
95
What synthesis of epinephrine occurs in the vesicles
Dopamine’s.- - - - - -> Epinephrine
96
Describe the release of Epinephrine
• AP goes through the membrane • Once AP gets to the axon, it opens up Ca2+ gated channels and causes an influx • The excess Ca2+ pulls the vesicle to the end of the membrane The vesicle fuses to the membrane, exocytosis occurs and Epinephrine is released
97
How does Epinephrine carry out its functions
By binding to adrenergic receptors
98
Describe the metabolism of epinephrine
It either goes back into the neuron(reuptake) and metabolized by MAO Or it’s metabolized by COMT at the liver(target organ)
99
What drug inhibits the synthesis of Epinephrine
Methyl tyrosine inhibits conversion of tyrosine to DOPA
100
What inhibits the storage of epinephrine
Reserpine blocks VMAT from taking epinephrine
101
What blocks the release of epinephrine
Guanethidine and Bratylium
102
What stimulates the release of epinephrine
Amphethamine
103
What inhibits the metabolism of epinephrine
MAOI And COMT Inhibitors
104
What inhibits the reuptake of NE
Cocaine Tricyclic antidepressants

Pharmacology GPP (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions