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Biochem 2 > 13. Noradrenergic neurotransmission > Flashcards

13. Noradrenergic neurotransmission Flashcards

1
Q

What does the chemical group that monoamin neurotransmitters belong to?

A

One aminogroup derived from aromatic amino acids through decarboxylation

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2
Q

What are 2 examples of monoamine neurotransmitters groups?

A

1/ Catecholamines
2/ Indolamines

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3
Q

What are some examples of Catecholamines?

A

1/ noradrenaline/norepinephrine (adrenaline/epinephrine)
2/ dopamine

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4
Q

What is an example of Indolamines?

A

serotonine

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5
Q

What is the structure of Cathecholamines

A

cathecol (benzene diol) plus amine-containing side chain

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6
Q

What are Cathecholamines synthesized from?

A

They are synthesized from tyrosine (phenylalanine)

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7
Q

What are some chemical characteristics of Cathecholamines?

A

poorly absorbed and are degraded in the stomach can not cross the blood brain barrier

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8
Q

Where can you find Noradrenaline - norepinephrine (neurotransmitter)?

A

– brain
- postganglionic sympathetic neurons
- small amount in the circulation as a hormon

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9
Q

Where can you find Adrenaline - epinephrine (hormone)?

A
  • from the adrenal medulla
  • in small portion of neurons in the central nervous system
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10
Q

Where can you find Dopamine (neurotransmitter)?

A

– brain modulator
– in the periphery (kidney)

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11
Q

Identify this molecule

A

L-DOPA
=> 3,4-Dihydroxy-L-phenylalanine

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12
Q

Identify this molecule

A

Dopamine
-> 3-4-dihydroxy-phenethylamine

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13
Q

Identify this molecule

A

Noradrenaline – norepinephrine

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14
Q

Identify this molecule

A

Adrenaline – epinephrine

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15
Q

Tyrosine synthesis
-> Identify this molecule

A

5,6,7,8 - Tetrahydrobiopterin

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16
Q

Tyrosine synthesis
-> Identify 1 & 2

A

1/ Dihydrobiopterin reductase
2/ Phenylalanine hyroxylase

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17
Q

What are the consequences of tetrahydrobiopterin deficiency?

A

Dopamine
Noradrenaline
Serotonine

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18
Q

Tyrosine synthesis
-> What are consequences of PAH deficiency?

A

classic PKU
1:8000-9000
phenylpyruvate, phenyllactate
phenylacetate
Therapy: diet

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19
Q

What are Amino acid derivatives?
-> What is the role of Tyrosine hydroxylase?

A

Tyrosine hydroxylase can catalyse phenylalanine
➔ tyrosine conversion

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20
Q

What is the enzyme involving in melanin synthesis?

A

melanocyte specific copper-dependent tyrosinase

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21
Q

Noradrenergic synapse
-> What is the role of AMPT?

A

It inhibits tyrosine hydroxylase and norepinephrine synthesis

(AMPT (alpha-methyl-para-tyrosine) is an inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis.)

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22
Q

Noradrenergic synapse
-> What is the role of Reserpine?

A

It inhibits VMAT (Vesicular monoamine transporter) and depletes norepinephrine stores

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23
Q

Noradrenergic synapse
-> What is the role of NRI?

A

Antidepressant that inhibit the norepinephrine transporter (same with SNRI)

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24
Q

Noradrenergic synapse
-> What is the role of SNRI?

A

Antidepressant that inhibit the norepinephrine transporter (same with NRI)

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25
Q

Noradrenergic synapse
-> What is the role of Tropolone?

A

It inhibits COMT

(Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines, catecholestrogens, and various drugs and substances having a catechol structure)

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26
Q

Noradrenergic synapse
-> What is the role of Prazosin?

A

An alpha-1 antagonist

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27
Q

Noradrenergic synapse
-> What is the role of MAOI?

A

An antidepressant inhibiting MAO(A)

(An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain.)

28
Q

Noradrenergic synapse
-> What is the role of Yohimbine?

A

What is an alpha 2 antagonist

29
Q

Noradrenergic synapse
-> What is the role of Propranolol?

A

a Beta antagonist

30
Q

Synthesis of Dopamine

A
31
Q

Synthesis of Noradrenaline

A
32
Q

Synthesis of Adrenaline

A
33
Q

What is tyrosine hydroxylase?

A

a mixed function oxygenase (monooxygenase)

Rate limiting enzyme. (Catecholamines: negative feedback)

Activation by Ca2+ (Ca2+/calmodulin-dependent kinase)

During increased sympathetic activity – increased tyrosine hydroxylase activity

34
Q

What is the role of L-DOPA in therapy?

A

Parkinson’s disease

35
Q

The role of Dopa-decarboxylase inhibitors?

A

L-DOPA → Parkinson’s disease

36
Q

The role of α-metil-DOPA inhibitors?

A

α-metil-DOPA → hypertension therapy (α2-receptor-agonist)

37
Q

Uptake of norepinephrine/epinephrine/dopamine into synaptic vesicles
-> Characteristics of VMTA 2 (VMAT: vesicular monoamine transporter)

A

VMTA 2 (VMAT: vesicular monoamine transporter)
vesicular membrane transporter 2

(-12 transmembrane domain)
NE -broad substrate-specificity to E biogenic amines
DA (triptamine, tiramine, amfetamin – compete with endogenous catecholamine)

(-high affinity for reserpine irreversible inhibitor
– depletion of vesicles)

(-altered VMTA2 expression in bipolar disease
(lithium influences)

38
Q

Uptake of catecholamines by presynaptic terminals

A
  • Active transport
  • Na+ cotransport (secondary active transport)
  • Sustained depolarization
    *→ reverse function
39
Q

What are Inhibitors for Uptake of catecholamines by presynaptic terminals?

A

Cocain
tricyclic antidepressant

40
Q

Relative harmfulness of drugs
-> The role of cocaine?

A

inhibits noradrenaline, dopamine serotonine reuptake

41
Q

What happen during Cocaine intoxication?

A

Alpha and beta adrenerg receptor stimulation
Hypertension, tachycardia, chest pain Agitated, tremulous

Treatment: benzodiazepines

42
Q

Treatment for cocaine intoxication

A

benzodiazepines

43
Q

What is The mode of action of amphetamine?

A

an indirectly acting sympathomimetic amine: Non-exocytotic release of NA

44
Q

What happen during Non-exocytotic release of NA?

A

NA release, MAO – monoamine oxidase inhibitor, NET inhibitor,

45
Q

Catabolism of catecholamines
-> most of the released noradrenaline recaptured by ____

A

NET (Sodium- dependent noradrenaline transporter SLC6A2)

(MAO – monoamine oxidase
COMT – catechol oxymethyl transferase)

46
Q

Describe Catabolism of catecholamines?

A

(MAO A) in the gastrointestinal tract and liver – prevents access of ingested indirectly acting amines (e.g. tyrosine➔tyramine) to the general circulation

47
Q

Patients on monoamine oxidase inhibitors (especially MAO-A inhibitors or non- selective MAO inhibitors) are advised to avoid ___ (what food?)

A

tyramine rich foods.

48
Q

Name of a MAO – monoamine oxidase inhibitor?

A

Cigarette smoke

49
Q

What are the 2 Enzymes in the metabolism of noradrenaline?

A

MAO – monoamine oxidase
COMT – catechol oxymethyl transferase

50
Q

The role of MAO – monoamine oxidase

A

oxidative deamination of catecholamines (adrenaline, noradrenaline, dopamine, serotonine)

51
Q

The role of COMT – catechol oxymethyl transferase

A

COMT: methyl transfer to the 3-hydroxy group on the ring from S-adenosylmethionine (SAM)
(adrenaline, noradrenaline, dopamine)
(multiple location: brain, liver, kidney)

52
Q

What is Pheochromocytoma?

A

Most common tumor of the adrenal medulla in adults Derived from chromaffin cells
Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension.

53
Q

Episodic hyperadrenergic symptoms (5 P’s):

A

Pressure (high BP)
Pain (headache)
Perspiration
Palpitations (tachycardia)
Pallor

54
Q

Therapy for Pheochromocytoma

A

α antagonist (non-selective, irreversible)
Surgery

55
Q

The main pathways of noradrenaline metabolism
-> Identify 1 - 2

A

1/ VMA: Vanillin-mandulasav
2/ MPHG

56
Q

The main pathways of noradrenaline metabolism
-> Identify 1 - 2

A

1/ NM: normetanephrine
2/ NA: noradrenaline

57
Q

The main pathways of noradrenaline metabolism
-> Identify enzyme a & b

A
58
Q

The main pathways of noradrenaline metabolism
-> Identify enzyme a & b

A

a/ AR: Aldehyde reductase
b/ ADH: aldehyde dehydrogenase

59
Q

For the synthesis of dopamine, epinephrine and norepinephrine
-> which reaction is the rate-limiting step?

A

The synthesis of DOPA from Tyrosine
-> catalyzed by tyrosine hydroxylase

60
Q

How can step 1 be activated?

A

activation by phosphorylation: Ca2+/calmodulin-dependent kinase PKA, PKC, PKG

61
Q

The main pathways of noradrenaline metabolism
-> What is the synthesis location of Dopamin

A

Cytosol

62
Q

The main pathways of noradrenaline metabolism
-> What is the synthesis location of Epinephrine

A

Cytosol

63
Q

The main pathways of noradrenaline metabolism
-> What is the synthesis location of Norepinephrine

A

Synaptic vesicles

64
Q

The adrenal medulla releases ___ and ____ into the bloodstream

A

epinephrine (adrenaline) and norepinephrine (noradrenaline)

65
Q

Cellular view of catecholamine synthesis.
-> ____ synthesizes and stores epinephrine in a sequence of four enzymatic and three transport steps

A

The chromaffin cell

66
Q

Cellular view of catecholamine synthesis. The chromaffin cell synthesizes and stores epinephrine in a sequence of four enzymatic and three transport steps
-> What are they?

A

AADC, amino acid decarboxylase; DA, dopamine; DBH, dopamine b-hydroxylase; Epi, epinephrine; NE, norepinephrine; TH, tyrosine hydroxylase.

Biochem 2 (38 decks)

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