Chemicals in the brain part 2 Flashcards

1
Q

What are the 4 monoamines (molecules containing only 1 amine) that we need to know?

  1. GABA, adrenaline, noradrenaline, serotonin
  2. dopamine, adrenaline, noradrenaline, kinesin
  3. dopamine, adrenaline, kinesin, serotonin
  4. dopamine, glutamate, noradrenaline, serotonin
A
  1. dopamine, adrenaline, noradrenaline, serotonin
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2
Q

Tyrosine is a non-essential (body can make it) amino acid that the body is able to synthesise from phenylalanine, which is an essential (body cannot make it) amino acid. What is the importance of tyrosine in relation to neurotransmitters?

A
  • crucial for the synthesis of monoamines dopamine, noradrenaline and adrenaline
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3
Q

Organise the synthesis pathway of dopamine, noradrenaline and adrenaline from tyrosine using the labels below:

    • adrenaline
    • L-DOPA
    • tyrosine non-essential amino acid
    • dopamine
    • noradrenaline
A
  1. tyrosine non-essential amino acid
  2. L-DOPA
  3. dopamine
  4. noradrenaline
  5. adrenaline
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4
Q

The synthesis pathway of dopamine, noradrenaline and adrenaline all begin with tyrosine, and can be viewed in the image below. The enzymes in the image below determine which monoamine is created, but how is this determined in the body? In essence what stops all neurotransmitters becoming adrenaline along the synthesis pathway?

A
  • the specific enzyme that is present
  • some neurons contain all the enzymes and some do not
  • neurotransmitter will be synthesised based on what is present
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5
Q

The synthesis pathway of dopamine, noradrenaline and adrenaline all begin with tyrosine, and can be viewed in the image below. The enzymes in the image below determine which monoamine is created. This is determined by which enzymes are present. For example, some neurons contain all the enzymes and some do not. A specific neurotransmitter will be synthesised based on what is present. Although we do not need to know all the enzymes in the image below, which one should we know that is also a target for drug treatments in Parkinsons disease outside the brain, which has low levels of domaine?

  1. tyrosine hydroxylase
  2. aromatic L-amino acid decarboxylase
  3. dopamine B-hydroxylase
  4. lactate dehydrogenase
A
  1. aromatic L-amino acid decarboxylase (also known as DOPA decarboxylase)
  • crucial for converting L-DOPA to dopamine
  • parkinsons medication inhibits DOPA decarboxylase, meaning more L-DOPA can move into the brain and increase dopamine levels
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6
Q

What are some of the roles of dopamine in the body?

A
  • movement (parkinsons direct and indirect pathways)
  • reward/addicitions sensations (mesolimbic system)
  • emotion (mesolimbic system)
  • cognitive function (mesocortical)
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7
Q

Due to the synthesis pathway of dopamine, noradrenaline and adrenaline, what can happen if you change one of the catecholamines?

A
  • downstream monoamines are affected
  • for example, if lots of dopamine is produced, may limit the levels of noradrenalin and adrenaline
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8
Q

In the synthesis of dopamine, noradrenaline and adrenaline, which enzyme is crucial for converting L-DOPA into dopamine?

  1. tyrosine hydroxylase
  2. aromatic L-amino acid decarboxylase
  3. dopamine B-hydroxylase
  4. lactate dehydrogenase
A
  1. aromatic L-amino acid decarboxylase, also known as DOPA decarboxylase
  • removes COOH group from L-DOPA
  • important for inhibiting conversion of L-DOPA to dopamine outside the brain
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9
Q

Tyrosine is a non-essential (body can make it) amino acid that the body is able to synthesise from phenylalanine, which is an essential (body cannot make it) amino acid. It is crucial for the synthesis of monoamines dopamine, noradrenaline and adrenaline. Which monamine is not synthesised from tyrosine?

  1. dopamine
  2. adrenalin
  3. noradrenaline
  4. serotonin
A
  1. serotonin

commonly known as 5-hydroxytryptamine

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10
Q

There is an essential amino acid that cannot be synthesised in the body alone and must be consumed in the diet that is crucial for the synthesis of the monoamine neurotransmitter 5-hydroxytryptophan (serotonin). What is the amino acid called?

  1. tryptophan
  2. glutamate
  3. vitamin D
  4. phenylalanine
A
  1. tryptophan
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11
Q

What is the synthesis pathway for 5-hydroxy-tryptamine (5-HT or serotonin)?

A
  • tryptophan (hydroxyl group (OH) is added)
  • 5-hydroxy-tryptophan (CO2 is removed)
  • 5-hydroxy-tryptamine (5-HT or serotonin
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12
Q

5-hydroxy-tryptamine (5-HT or serotonin) can finally be synthesised into melatonin. What is melatonin important for?

  1. fight or flight response
  2. autonomic inhibition
  3. sleep
  4. muscle contraction
A
  1. sleep
    • used in drugs to treat sleep
    • turkey/milk have a lot of tryptophan which can be turned into melatonin, which maybe why you feel sleepy after eating/drinking them
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13
Q

How many dopamine receptors are there?

  1. 1
  2. 3
  3. 5
  4. 7
A
  1. 5
    - D1-D5
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14
Q

Dopamine receptors D1 and D5 belong to the D1 family. Which GCPR do they bind with?

  1. Gas
  2. Gaq
  3. Gai
  4. Gad
A
  1. Gas
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15
Q

Dopamine receptors D1 and D5 belong to the D1 family. They bind with Gas GCPR. What is the normal pathways of Gas?

A
  1. Gas increases adenylyl cyclase (AC)
  2. AC converts ATP into cAMP
  3. cAMP leads to increased protein kinase A
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16
Q

Dopamine receptors D2, D3 and D4 belong to the D2 family. Which GCPR do they bind with and what is their action?

  1. Gas
  2. Gaq
  3. Gai
  4. Gad
A
  • Gai
  • inhibit adenylyl cyclase and reduce cAMP
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17
Q

Are all the dopamine receptors ionotropic or metabotrophic?

A
  • metabotropic
  • means they require one or more metabolic step to induce intracellular pathway
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18
Q

In Parkinsons disease low or absent levels of dopamine have been linked with the disease. What are the 3 mechanisms that parkinsons disease medication aims to utilise that can increase dopamine levels?

A
  1. augmentation/increase levels of dopamine (↑ synthesis)
  2. agonists of dopamine
  3. inhibition of dopamine metabolism
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19
Q

Which alpha and beta receptors are responsible for the transmission of adrenaline and noradrenaline in the CNS and PNS?

A
  • a1 (Gaq) = PLC converts PiP2 into IP3 and DAG into Ca2+ and PKc
  • a2 (Gai) = inhibition of Gas
  • B1-B3 (all Gas) = adenylyl cyclase into cAMP and then PKa
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20
Q

a2 receptors which act on Gai GCPR are placed where on the synapse and what is their role?

  1. pre-synapse modulating glutamate release
  2. pre-synapse modulating catecholamine release
  3. post-synapse modulating glutamate release
  4. post-synapse modulating catecholamine release
A
  1. pre-synapse modulating catecholamine
    * modulates noradrenaline and adrenaline by inhibiting neuronal firing, so not release from active zone
21
Q

Due to the inhibitory nature of a2 receptors that act on the Gai GCPR, and their location on the pre synapse, what are a2 agonists commonly used as?

  1. sedation and anaesthetic
  2. excitation and anaesthetic
  3. sedation and sleep
  4. pain management and anaesthetic
A
  1. sedation and anaesthetic
22
Q

Out of all the a and b receptors, which is dominant in the forebrain?

A
  • b adrenoreceptors
23
Q

Anti depressants are used to try and increase noradrenaline levels in the forebrain. Although this can initially be a good thing, what can this cause long term?

  1. addiction to the medication
  2. up-regulation of B adrenoreceptors
  3. down regulation of B adrenoreceptors
  4. cytotoxicity
A
  1. down regulation of B adrenoreceptors
    * causes tolerance (need higher dose for same effect)
24
Q

Noradrenaline is an important neurotransmitter in the fight or flight response. What can activity of the noradrenergic cells in the brainstem contribute towards?

  • noradrenalin = mainly acts on alpha receptors
  • adrenalin = mainly synthesised by chromaffin cells in adrenal medulla
A
  • arousal and attention (important for survival)
  • can form part of ther reticular activating system
25
Q

In addition to contributing to arousal and attention, the noradrenergic system seems to facilitate what in the brain?

  1. responsiveness of other neurotransmitters in brain regions
  2. decreased sensitivity of other neurotransmitters in brain regions
  3. cytotoxicity of other neurotransmitters in brain regions
  4. inhibition of inhibitory neurotransmitters in brain regions
A
  1. responsiveness of brain regions to other neurotransmitter systems
26
Q

Drugs like cocaine and amphetamines are associated with blocking the re-uptake and increasing the synthesis of noradrenaline. Whilst this may be effective at increasing arousal and attention, if this acts on B receptors, what could some peripheral side effects be?

A
  1. increase HR
  2. myocardial contraction force
  3. lipolysis increasing blood glucose
  4. renin release causing increased BP

ALL IMPORTANT DURING FIGHT OR FLIGHT

27
Q

How many different 5-HT (serotonin) receptors are there?

A
  • 14
28
Q

There are 14 different 5-HT receptors. All 5-HT (serotonin) receptors (except 5-HT3) are a specific type of receptor, what type of receptors are they?

  1. ionotropic
  2. receptor tyrosine kinase
  3. metabotropic GPCR
  4. ligand gated
A
  1. metabotropic GPCR
29
Q

Some 5-HT (serotonin) receptors are autoreceptors, what are these?

A
  • a special group of receptors
  • regulate the pre-synaptic concentration and postsynaptic effects of neurotransmitters
  • inhibit transmitter release and synthesis (just like the 5HT-2A receptors that reduce dopamine in mesolimbic system)
30
Q

5-HT (serotonin) receptors are generally located where on the synapse?

  1. pre-synapse
  2. synaptic cleft
  3. action zone
  4. post-synapse
A
  1. post synapse
    - act here through serotonergic neurotransmission
31
Q

5-HT (serotonin) is important for a lot of functions, what are some of the most important?

A
  • pain
  • mood (depression)
  • nausea/vomitting
32
Q

Depression is associated with low levels of serotonin. What can a drug aim to do to treat this?

  1. inhibit serotonin release
  2. inhibit serotonin binding at post- synapse
  3. inhibit re-uptake of serotonin
  4. increase re-uptake of serotonin
A
  1. inhibit re-uptake of serotonin
  • selective serotonin re-uptake inhibitors (SSRIs)
    • increases levels of serotonin
33
Q

Schizophrenic is associated with high levels of serotonin. What can a drug aim to do to treat this?

  1. inhibit serotonin release
  2. partial agonist of serotonin
  3. inhibit re-uptake of serotonin
  4. inhibit serotonin binding at post-synapse
A
  1. partial agonist of serotonin
  • partial agonists cause a lower than normal response as would not want to stop it all together as other parts of brain need them
  • can be a combination of dual dopamine and serotonin antagonists
34
Q

Monamines (dopamine, noradrenaline, adrenaline and 5-HT (serotonin) are transported across plasma membranes at the synapse by plasma membrane transporters. Once the action potential has finished at the pre synapse, what is the main method by which the monamines are re-absorbed?

  1. re-uptake at the pre synapse and packaged back into vesicles
  2. re-cycled by astrocytes
  3. degraded by enzymes in synaptic cleft
  4. inhibition of post-synapse
A
  1. re-uptake at the pre synapse and packaged back into vesicles
35
Q

Monaminse (dopamine, noradrenaline, adrenaline and 5-HT (serotonin) are transported across plasma membranes at the synapse by plasma membrane transporters. The main method by which the monamines signal is terminated is by re-uptake at the pre synapse and packaging back into vesicles. What are the other 2 methods by which signal termination can be achieved?

A

1 - re-absorbed by astrocytes (glial cells) (minority)

2 - metabolism by enzymes in synaptic cleft or pre synapse

36
Q

Monaminse (dopamine, noradrenaline, adrenaline and 5-HT (serotonin) are transported across plasma membranes at the synapse by plasma membrane transporters. The main method by which the monamines signal is terminated is by re-uptake at the pre synapse and packaging back into vesicles. They can also be metabolised by enzymes in synaptic cleft or pre synapse. What are the 2 main enzymes responsible for this?

  1. MAO (isoforms A and B) and COMT
  2. MAO (isoforms A and B) and lactate dehydrogenase
  3. MAO (isoforms A and B) and dopa-decarboxylase
  4. dopa-decarboxylase and COMT
  • MAO = monoamine oxidase
  • COMT = catechol-O-methyl transferase
A
  1. MAO (isoforms A and B) and COMT
37
Q

Monaminse (dopamine, noradrenaline, adrenaline and 5-HT (serotonin) are transported across plasma membranes at the synapse by plasma membrane transporters. The main method by which the monamines signal is terminated is by reuptake at the pre synapse and packaging back into vesicles. They can also be metabolism by enzymes in synaptic cleft or pre synapse. The 2 main enzymes responsible for this are monoamine oxidase (MAO – A/B) and catechol-O-methyl transferase (COMT). Why is it important to know the enzymes responsible for metabolising the monoamines?

A
  • MAO (isoforms A and B) and COMT are the rate limiting steps
  • inhibition of MAO and COMT decreases breakdown and re-absorption of monoamines
  • drug targets for increasing monamine levels
38
Q

What 2 things are used to create acetylcholine?

A
    • acetyl CoA and choline (essential nutrient consumed in diet)
  • stored as phosphatidycholine in cell membranes
39
Q

Acetylcholine acts on cholinergic (hence the name with choline in) receptors, what are the 2 types of receptors we need to know about, and are these ionotropic or metabotropic?

A

1 - nicotinic = ionotropic (Nn (neuron to neuron) and Nm (neuron to muscle))

2 - muscarinic = metabotropic (M1-M5)

40
Q

Are cholinergic receptors predominantly para or sympathetic in nature?

A
  • parasympathetic where it acts on both preganglionic and postganglionic neurons
  • excitatory for rest and digest
41
Q

The majority of cholinergic receptors are predominantly para-sympathetic in nature, acting on both preganglionic and postganglionic neurons. Are cholinergic receptors involved in the sympathetic system?

A
  • yes
  • preganglionic = ACh binds
  • postganglionic = metabotropic and adrenalin and noradrenalin bind
42
Q

Acetylcholine (ACh) is unlike other monoamines and it is not taken up by astrocytes or at the pre-synapse. How is the ACh signal generally terminated?

A
  • enzyme acetylcholinesterase degrades ACh in synaptic cleft
  • degrades into choline (can then be recycled into pre synapse) and acetyl CoA
43
Q

We have stores of choline in the body if we ever need to synthesise higher levels of ACh. What are these stores?

  1. phosphatidylcholine
  2. HDL
  3. LDL
  4. phospholipase
A
  1. phosphatidylcholine found in cellular membranes
44
Q

Choline acetyltransferase is a transferase enzyme that is the rate limiting step for the synthesis of a neurotransmitter. Which neurotransmitter is this enzyme responsible for synthesising and what 2 things does it combine?

A
  • acetylcholine
  • combines choline and acetyl group from the coenzyme acetyl-CoA
45
Q

In order to synthesis ACh, what is the rate limiting step that is often the target for drugs?

  1. choline acetyltransferase
  2. monoamine oxidase
  3. catechol-O-methyl transferase
  4. dopa-decarboxylase and COMT
A
  1. choline acetyltransferase
    - transfers acetate ion from acetyl CoA to choline
46
Q

Where does the majority of acetyl CoA come from in the synthesis of ACh?

A
  • glycolysis (formation of energy from glucose)
47
Q

Where are the 2 types of nicotinic receptors found?

A
  • Nn = neuron to neuron, ganglia (all pre-ganglionic)
  • Nm = neuromuscular junctions (post-ganglionic)
48
Q

What are some of the main functions of ACh?

A
  • cognition
  • attention/sleep
  • suppression of pain
  • epilepsy