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MRCPsych Part A big > Neurochemistry > Flashcards

Neurochemistry Flashcards

1
Q

What are the roles of the presynaptic neuron?

A

Synthesis, transports and stores neurotransmitter.

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2
Q

Where does synthesis of neurotransmitter take place?

A

Cell body/soma

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3
Q

What happens to the neurotransmitter once it is synthesized?

A

Axonal transport to synaptic terminal and storage in synaptic vesicle.

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4
Q

By which processes are neurotransmitters released?

A

Membrane fusion

Ecxocytosis

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5
Q

What happens once a neurotransmitter is released?

A

Occupies receptors on the surface of the postsynaptic neuronal membrane.

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6
Q

What is autoreceptor activity?

A

When neurotransmitter molecules are also receptors on the presynaptic neuronal membrane.

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7
Q

Why is autoreceptor activity important?

A

For feedback inhibition of neurotransmitter release and synthesis.

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8
Q

What is saturation?

A

More neurotransmitters than receptors

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9
Q

Which neurotransmitters are more likely to bind to receptors?

A

The ones of which there is a high er concentration.

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10
Q

What is an irreversible neurotransmitter?

A

One that once bound to a receptor, produces irreversible structural alterations in the protein of the receptor complexes.

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11
Q

How does cessation of neurotransmitter action take place?

A

Reuptake back to presynaptic neuron
Enzymatic breakdown at the cleft
Removal by glia or plasma circulation

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12
Q

GIve an example of transporters that reuptake neurotransmitters

A

Monoamine transporters

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13
Q

Give an example of enzyme that breaks down neurotransmitters at the cleft

A

COMT/MAO-A enzyme

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14
Q

Name the monoamines

A 
Dopamine
Norepinephrine
Epinephrine
Serotonin
Acetylcholine
Histamine
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15
Q

Name the amino acid neurotransmitters

A

GABA
Glycine
Glutamate

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16
Q

Name the peptides

A 
Endorphins
Cholecystokinin
Neurotensin
Neuropeptide Y
Leptin
Ghrelin
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17
Q

What type of neurotransmitter is Acetylcholine?

A

Monoamine

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18
Q

What type of neurotransmitter is GABA?

A

Amino acid

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19
Q

What type of neurotransmitter is endorphin?

A

Peptide

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20
Q

How are receptors classified?

A

Ligand-gated (ionotropic)
Metabotropic
Ligand-dependent regulars of nuclear transcription

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21
Q

How do ionotropic receptors work?

A

Binding of chemical messenger alters probability of opening of transmembrane pores or channels

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22
Q

How do metabotropic receptors work?

A

Receptor proteins are coupled to intracellular G proteins as transduscing elements

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23
Q

Which type of receptor leads to a fast response?

A

Ionotropic

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24
Q

Gave examples of medications that lead to ionotropic response?

A

GABAa benzo

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25
Q

Give e.g. of medications that lead to metabotropic response

A

Most antipsychotics

Antidepressants

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26
Q

What is the structure of ion channel receptors?

A

4-5 protein subunits make up a pore like structure.
Each protein subunit is a string of amino acids which passes in and out of the cell membrane four times.
At the extracellular end of this string is a N-terminal, which mediates GABA-channel interactions.
In the middle of the string is a large intracellular loop of amino acids with four sites where phosphorylation occurs.

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27
Q

Where is the N terminal in an ion channel receptor?

A

Extracellular end of the amino acid string

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28
Q

What ion do inhibitory neurotransmitter action lead to?

A

Chloride

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29
Q

What ion do excitatory neurotransmitter lead to?

A

Calcium

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30
Q

What are some ionotropic receptors?

A

GABAa
NMDA
5HT3

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31
Q

Structure of G-protein-coupled metabotropic receptors

A

Proteins that span cell membrane seven times.

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32
Q

How do G0protein-coupled metabotropic receptors act?

A

Via cyclase mediated second messenger activation - GTP, ATP etc.

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33
Q

Which proteins are stimulatory in metabotropic receptors?

A

Gs-proteins

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34
Q

Which proteins are inhibitory in metabotropic receptors?

A

Gi-protein

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35
Q

What is a third way that G-protein receptors can act?

A

Via phospholipase C

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36
Q

How do metabotropic receptors cause longer lasting effects?

A

Influence protein synthesis.

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37
Q

Give e.g. of metabotropic receptors

A

Dopamine receptors
Most 5HT receptors except 5HT3
Adrenergic receptors
Opioid receptors

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38
Q

Structure of nuclear receptors

A

Cysteine-rich DNA-binding domain, ligand-binding domain and variable amino terminal region.

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39
Q

How do nuclear receptors work?

A

Upon appropriate ligand binding, a nuclear receptor becomes a transcription factor and binds to DNA via zinc fingers.

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40
Q

What is a transcription factor?

A

A nuclear receptor once ligand binding has occurred.

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41
Q

How does a transcription factor bind to DNA?

A

Via zinc fingers

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42
Q

Give e.g. of nuclear receptors

A 
Receptors for:
Glucocorticoid
Progesterone
Androgen
Vitamin D
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43
Q

Source of dopamine

A

Tyrosine -> L-Dopa -> Dopamine

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44
Q

Rate limiting step of formation of dopamine

A

Tyrosine hydroxylase

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45
Q

Breakdown enzymes of dopamine

A

MAO
COMT
MAO-A - selective for norepinephrine and seretonin
MAO-B - selective for dopamine

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46
Q

Breakdown product of dopamine

A

Homovanillic acid

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47
Q

How is dopamine re-uptaked?

A

Dopamine transporter

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48
Q

What drug inhibits re-uptake of dopamine?

A

Cocaine

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49
Q

Function of dopamine

A 
Motivation
Novelty seeking
Reward - addictions
Arousal
Motor - basal ganglia
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50
Q

Receptors of dopamine

A

D1 to D5
All G-protein coupled.
D1 exclusively postynaptic - resistant to antagonism
D5 more limbic in distribution and 10x higher dopamine affinity.
D4 mainly in frontal cortex, high affinity for clozapine.
D4 selective antagonists do not have antipsychotic efficacy.

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51
Q

Which dopamine receptors are inhibitory?

A

D2 to D5

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52
Q

How to D2 to D5 cause inhibition?

A

Decrease adenylate cyclase

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53
Q

Which dopamine receptor has high affinity with clozapine?

A

D4

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54
Q

What disorder can low dopamine cause?

A

Parkinsons

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55
Q

What disorder can high dopamine cause?

A

Psychosis - particularly if in mesolimbic area.

If in mesocortical area - negative symptoms

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56
Q

Where does high dopamine levels suggest psychosis?

A

Mesolimbic area

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57
Q

Where does high dopamine levels suggest negative symptoms of schizophrenia?

A

Mesocortical

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58
Q

Source of noradrenaline?

A

Tyrosine -> L-dopa -> dopamine -> norepinephrine -> epinephrine

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59
Q

Rate limiting step of noradrenaline?

A

Tyrosine hydroxylase

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60
Q

Synthetic enzymes for noradrenaline

A

Dopamine-b-hydroxylase modulates production.

Phenylethanolamine-N-methyltransferase modulates conversine of norepinephrine to epinpherine.

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61
Q

Which enzyme changes norepinephrine to epinephrine?

A

Phenylethanolamine-N-methyltransferase

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62
Q

Breakdown enzyme of noradrenaline?

A

MAO-A

COMT

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63
Q

Breakdown product of noradrenaline?

A

3-methoxy-4-hydroxyphenylglycol (MHPG)

Vanillyl mandelic acid (VMA)

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64
Q

What is the major metabolite of noradrenaline in the CNS?

A

MHPG

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65
Q

What is the major metabolite if noradrenaline in the endocrine/peripheral nervous system?

A

VMA

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66
Q

How is noradrenaline re-uptaked?

A

Noradrenaline reuptake channel

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67
Q

What drugs inhibit reuptake of noradrenaline?

A

Tricyclics
SNRIs
Reboxetine
Bupoprion (noradrenaline-dopamine reuptake inhibitor)

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68
Q

Function of noradrenaline?

A

Arousal
Anxiety
Mood regulation
Autonomic mediatino

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69
Q

Receptors for noradrenaline

A

Alpha 1, Alpha 2, Beta 1, Beta 2

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70
Q

Describe alpha 1 receptors for noradrenaline

A

Phospholipase C coupled

Mostly postsynaptic

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71
Q

Describe alpha2 receptors for noradrenaline

A

Gi-coupled

Mostly presynaptic autoreceptors

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72
Q

Describe beta receptors for noradrenaline

A

GS-coupled
Predominate in locus cereulus
Regulate arousal

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73
Q

Describe beta 1 receptors for noradrenaline

A

High affinity to noradrenaline

Mostly peripheral Gs protein coupled

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74
Q

Describe beta 2 reeptors for noradrenaline

A

High affinity for epinephrine

peripheral

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75
Q

Which noradrenaline receptor has high affinity for adrenaline?

A

Beta 2

76
Q

Disorders in which low levels of noradrenaline is seen?

A

Depression

77
Q

Disorders in which abnormal levels of noradrenaline is seen?

A

Panic and anxiety disorders

78
Q

Source of seretonin?

A

Tryptophan ->(tryptophan hydroxylase) 5 hydroxy 1-trytophan -> (tryptophan decarboxylase/ aromatic L-amino acid decarboxylase) ->seretonin

79
Q

Rate limiting step of seretonin

A

Availability of tryptophan

80
Q

Rate limiting synthetic enzyme for serotonin

A

Tryptophan hydroxylase (based on availability of tryptophan)

81
Q

Breakdown enzyme of seretonin

A

MAO-A

82
Q

Break-down product of seretonin

A

5-hydroxyindoleaetic acid (5-HIAA)

83
Q

What allows reuptake of seretonin?

A

Seretonin reuptake channel

84
Q

What drugs inhibits seretonin reuptake?

A

Tricycles
SNRIs
SSRIs

85
Q

Function of seretonin

A 
Mood
Perception of pain
Feeding
Sleep-wake cycle
Motor activity
Sexual behaviour
Temperature regulation
86
Q

Receptors for seretonin

A

14 known subtypes

87
Q

Which seretonin receptors are C-protein coupled?

A

All except 5 HT-3

88
Q

Which seretonin receptor is in the gut?

A

5HT3

89
Q

Describe 5HT1a receptors

A

Gi coupled postsynaptic.
Antidepressant response.
Sexual behaviour.

90
Q

Describe 5HT1B receptors

A

Gi coupled presynaptic.

91
Q

Describe 5HT1D receptors.

A

Gi coupled, both pre and postsynaptic.

92
Q

Describe 5HT2 receptors

A

Phospholipase C coupled.
Postsynaptic.
Antagonism can lead to antipsychotic response (atypicals) and sedation.

93
Q

Which seretonin receptor can be stimulated by LSD?

A

5HT2

94
Q

Which seretonin receptor is downregulated after antidepressant or ECT treatment?

A

5HT2

95
Q

Which seretonin receptor can lead to a response from atypical antipsychotics if antagonised?

A

5HT2

96
Q

Which seretonin receptor is involved with regulation of circadian rhythym?

A

5HT7

97
Q

Describe disorders related to low seretonin levels

A

Depression
Aggression
Suicide
Impulsivity

98
Q

How do seretonin levels have a role in psychosis?

A

Regulate dopamine system

99
Q

Which medication is an agonist on 5HT1a?

A

Antidepressant

100
Q

Which medication is a partial agonist on 5HT1a?

A

Anxiolytics

101
Q

What action can 5HT1B receptor lead to?

A

Aggression

102
Q

Which medication is an antagonist for 5HT1D?

A

Antimigraine

103
Q

Which medication is an antagonist for 5HT2A?

A

Antipsychotic

104
Q

Which medication is an agonist for 5HT2A?

A

Hallucinogens

105
Q

Which seretonin receptor is involved in working memory, platelets and smooth muscle

A

5HT2A

106
Q

Which receptor stimulation (seretonin) may result in cardiac valvular fibrosis

A

5HT2B - dexfenfluramine

107
Q

What effect can stimulation of 5HT2C have?

A

Anxiogenic and anorexic effect

108
Q

What medication has an antagonistic effect on 5HT3?

A

Antiemetic

109
Q

Which medication has an antagonistic effect on 5HT6?

A

Antipsychotic

Antidepressant

110
Q

Which serotinin receptor helps as an antiemetic?

A

Antogonist of 5HT3

111
Q

Which seretonin receptor can act as antimigraine?

A

Antagonist to 5HT1D

112
Q

What is DOPA decarboxylase involved in?

A

Synthesis of dopamine and seretonin.

113
Q

How does DOPA decarboxylase form dopamine?

A

Tyrosine -> hydroxylation -> L-dopa -> catalyses by tyrosine hydroxylase -> DOPA decarboxylase decarboxylates L-DOPA to form dopamine.

114
Q

Where is dopamine produced by the DOPA decarboxylase enzyme?

A 
Basal ganglia (substantia nigra, ventral tegmental area, and hypothalamus)
Sympathetic nervous system.
115
Q

What is dopamine the precursor of?

A

Catecholaminergic hormones, noradrenaline and adrenaline in adrenal medulla.

116
Q

Describe the production of serotonin

A

Tryptophan hydroxylase produces 5-PH tryptophan, which is decarboxylated by tryptophan decarboxylase, forming seretonin.

117
Q

Which type of enzyme is DOPA decarboxylase?

A

Homodimeric
Pyridoxal
Phosphate-dependent

118
Q

Source of acetylcholine?

A

Choline and acetyl-coenzyme A

119
Q

Rate limiting step of formation of acetylcholine?

A

Availability of choline

120
Q

Synthetic enzyme for acetylcholine?

A

Choline acetyltransferase

121
Q

Breakdown ezymes for acetylcholine?

A

Acetylcholinesterase - rapid

122
Q

Breakdown product of acetylcholine?

A

Choline

123
Q

Reuptake of acetylcholine?

A

None.

124
Q

Function of acetylcholine?

A 
Modulate arousal
Learning
Memory
Rapid eye movement sleep
Pain perception
Thirst
Parasympathetic mediation
125
Q

acetylcholine receptors?

A

Muscarinic (M1 - M5) - G-protein coupled.

Nicotinic - ion channels.

126
Q

Where are nicotinic, acetylcholine receptors more common?

A

Peripheral parasympathetic system

127
Q

What do muscarinic acetylcholine receptors do?

A

Centrally mediate attention/learning/potentiation

Post synaptic in parasympathetic nervous system to produce parasympathetic effects (see M1 to M5 breakdown)

128
Q

Disorders where there is reduced acetylcholine?

A

Alzheimers

129
Q

How is acetylcholine involved in Parkinsons?

A

Involved in dopamine balance

130
Q

Source of GABA

A

Glutamic acid

131
Q

Rate limiting step for formation of GABA

A

Glutamic acid decarboxylase

132
Q

Synthetic enzymes involved in formation of GABA?

A

Glutamic acid decarboxylase

133
Q

Breakdown enzyme for GABA

A

GABA transaminase

134
Q

Breakdown product of GABA?

A

Glutamate, then succinic acid

135
Q

Reuptake of GABA?

A

Presynaptic nerve terminals
Glial cells
Uptake is bidirectional and temperature and ion-dependent.

136
Q

What inhibits GABA reuptake?

A

Tiagabine

137
Q

Function of GABA?

A

Mediates anxiety

Seizure cessation

138
Q

In which medications is GABA involved in?

A

Benzo
Barbituates
EtOH

139
Q

Receptors for GABA

A

GABAa and GABAb

140
Q

Function of GABAa

A

Opens chloride channel, leading to hyperpolarization (inhibitory).

141
Q

Structure of GABAa receptor?

A

5 subunits, at least 14 subunits.

142
Q

Structure of GABAb receptor

A

G-protein coupled.

143
Q

Selective agonist of GABAb receptor?

A

Baclofen

144
Q

Disorders of GABA?

A

Anxiety disorders
Alcoholism
Epilepsy
Huntington’s

145
Q

Source of glutamate?

A
  1. 2-oxoglutarate and aspartate by aspartate aminotransferase or
  2. glutamine by glutaminse or
  3. 2-oxoglutarate by ornithine aminotransferase.
146
Q

Regulation of gluamate?

A

Accummulation of precursors or end-product inhibition

147
Q

Synthetic enzyme for gluamate?

A

Glutaminase

148
Q

Breakdown enzymes for gluamate?

A

Glutamate dehydrogenase

Glutamine synthetase

149
Q

Breakdown product of gluamate?

A

Glutamine or alpha-ketoglutarate

150
Q

Reuptake of glutamate?

A

Glial with conversion to glutamine

151
Q

Function of glutamate?

A 
Metabolic:
Intermediary in oxidation, ammonia cycle.
Precursor of all GABA in CNS.
NMDA - memory acquisition.
Developmental plasticity.
Epilepsy.
Ischaemic brain injury.
152
Q

Receptors of glutamate

A

Metabotropic - 8 in total, 3 groups.

Ionotropic - NMDA and non-NMDA.

153
Q

Structure of metabotropic receptors for gluamate

A

Group I - mGluR1&mGluR5 are linked to phospholipase C.

154
Q

Structure of NMDA glutamate receptor

A

Subunits with distinct binding sites for glutamate, glycine, phencyclidine, magnesium, zinc.

155
Q

Structure of non-NMDA receptor for glutamate?

A

Kainate binding or AMPA type.

156
Q

Which glutamate receptor mediates long term potentiation?

A

NMDA

157
Q

Which disorders are linked to glutamate toxicity?

A

Stroke
Schizophrenia
Seizures

158
Q

What can NMDA antagonists cause?

A

Hallucinations - PCP, ketamine

159
Q

What is the primary inhibitory neurotransmitter in the spinal cord?

A

Glycine

160
Q

How is glycine synthesized?

A

From serine by serine trans-hydroxymethylase and glycerate dehydrogenase

161
Q

What are the rate-limiting steps of glycine production?

A

Serine trans-hydroxymethylase

Glycerate dehydrogenase

162
Q

Function of glycine

A

Mandatory adjunctive neurotransmitter for glutamate receptors

163
Q

What is the name of the excitatory glycine site on NMDA receptors?

A

Non-strychnine sensitive glycine receptor.

164
Q

What is the Non-strychnine sensitive glycine receptor?

A

Inhibitory receptor.

165
Q

Where is the Non-strychnine sensitive glycine receptor found?

A

Spinal cord

166
Q

How are glycine and schizophrenia linked?

A

Facilitating glycine transmission can reduce negative symptoms.

167
Q

What is the name of an experimental glycine reuptake inhibitor which is being trialled to reduce negative symptoms?

A

Bitopertin

168
Q

Name two endogenous cannabinoid substances

A

Anandamide - a weak ligand

Arachnidonylglycerl - strong ligand

169
Q

How are anandamide and Arachnidonylglycerl formed?

A

Arachidonic acid and ethanolamine

170
Q

What are the cannabinoid receptors?

A

Central - CB1

Peripheral - CB2

171
Q

What do both cannabinoid receptors bind?

A

Tetrahydrocannabinol - active ingredient of maraijuana.

172
Q

Functino of anadamide?

A

Lowers intraocular pressure
Decreases activity level
Relieves pain

173
Q

What are neurotrophins?

A

Substances that act as polypeptide growth factors influencing proliferation and differentiation of neurons and glial cells.

174
Q

Well-known neurotrophins?

A

Nerve growth factor
Brain derived neurotrophic factor
Neutotrophin 3 and 4

175
Q

What is the neurotrophin hypothesis?

A

Neurons compete during development for limited resource of growth factors.
Those neurons that are responsive (high affinity binding site) survive.
Incorrect targeting of axons may lead to apoptosis.

176
Q

Which neurotrophin is involved in long-term potentiation of memory?

A

Brain derived neurotrophic factor

177
Q

Which medications affect brain derived neurotrophic factor?

A

SSRI and ECT upregulate it.

178
Q

Which mutation causes reduced brain derived neurotrophic factor activity?

A

Single nucleotide polymorphism in BDNF gene on chromosone 11p13 results in aa substitune of valine with methionine at codon 66.

179
Q

What do humans with the 11p13 BDNF mutation have?

A

Impaired hippocampal activation and performance

180
Q

What is reduced to a greater extent in patients with hallucinations in Lewy body compared to those without?

A

Corticol choline acetyl transferase

181
Q

What can chronic antidepressant use lead to?

A

Induces a reduction in beta adrenoreceptor density around 2 weeks after treatment.

182
Q

What is Kapur’s aberrant salience theory?

A

In a normal person, role of mesolimbic dopamine is to attach significance to external stimulus or internal thought. This converts neutral info to attention grabbing.

183
Q

Implications for psychosis in aberrant salience theory?

A

In psychosis where this is high dopamine in mesolimbic system, insignificant events and perceptions receive inappropriate significance, resulting in delusions.

184
Q

What are the clinical implications of the aberrant salience theory?

A

Antipsychotics dampen the significance of abnormal experiences, but do not erase symptoms - they provide the platform for psychological resolution.

185
Q

Where is an increase in 5HT2A receptors most prominent in those with depression?

A

Dorsolateral prefrontal cortex

Platelets

186
Q

Effect of longterm antidepressant use on seretonin receptors

A

Reduce 5HT2 receptors

Increase 5HT1A function

MRCPsych Part A big (22 decks)

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