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MRCPsych Part A > 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 acids

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
Give e.g. of medications that lead to metabotropic response
Most antipsychotics | Antidepressants
26
What is the structure of ion channel receptors?
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.
27
Where is the N terminal in an ion channel receptor?
Extracellular end of the amino acid string
28
What ion do inhibitory neurotransmitter action lead to?
Chloride
29
What ion do excitatory neurotransmitter lead to?
Calcium
30
What are some ionotropic receptors?
GABAa NMDA 5HT3
31
Structure of G-protein-coupled metabotropic receptors
Proteins that span cell membrane seven times.
32
How do G0protein-coupled metabotropic receptors act?
Via cyclase mediated second messenger activation - GTP, ATP etc.
33
Which proteins are stimulatory in metabotropic receptors?
Gs-proteins
34
Which proteins are inhibitory in metabotropic receptors?
Gi-protein
35
What is a third way that G-protein receptors can act?
Via phospholipase C
36
How do metabotropic receptors cause longer lasting effects?
Influence protein synthesis.
37
Give e.g. of metabotropic receptors
Dopamine receptors Most 5HT receptors except 5HT3 NEN Opioid receptors
38
Structure of nuclear receptors
Cysteine-rich DNA-binding domain, ligand-binding domain and variable amino terminal region.
39
How do nuclear receptors work?
Upon appropriate ligand binding, a nuclear receptor becomes a transcription factor and binds to DNA via zinc fingers.
40
What is a transcription factor?
A nuclear receptor once ligand binding has occurred.
41
How does a transcription factor bind to DNA?
Via zinc fingers
42
Give e.g. of nuclear receptors
``` Receptors for: Glucocorticoid Progesterone Androgen Vitamin D ```
43
Source of dopamine
Tyrosine -> L-Dopa -> Dopamine
44
Rate limiting step of formation of dopamine
Tyrosine hydroxylase
45
Breakdown enzymes of dopamine
MAO COMT MAO-A - selective for norepinephrine and seretonin MAO-B - selective for dopamine
46
Breakdown product of dopamine
Homovanillic acid
47
How is dopamine re-uptaked?
Dopamine transporter
48
What drug inhibits re-uptake of dopamine?
Cocaine
49
Function of dopamine
``` Motivation Novelty seeking Reward - addictions Arousal Motor - basal ganglia ```
50
Receptors of dopamine
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.
51
Which dopamine receptors are inhibitory?
D2 to D5
52
How to D2 to D5 cause inhibition?
Decrease adenylate cyclase
53
Which dopamine receptor has high affinity with clozapine?
D4
54
What disorder can low dopamine cause?
Parkinsons
55
What disorder can high dopamine cause?
Psychosis - particularly if in mesolimbic area. | If in mesocortical area - negative symptoms
56
Where does high dopamine levels suggest psychosis?
Mesolimbic area
57
Where does high dopamine levels suggest negative symptoms of schizophrenia?
Mesocortical
58
Source of noradrenaline?
Tyrosine -> L-dopa -> dopamine -> norepinephrine -> epinephrine
59
Rate limiting step of noradrenaline?
Tyrosine hydroxylase
60
Synthetic enzymes for noradrenaline
Dopamine-b-hydroxylase modulates production. | Phenylethanolamine-N-methyltransferase modulates conversine of norepinephrine to epinpherine.
61
Which enzyme changes norepinephrine to epinephrine?
Phenylethanolamine-N-methyltransferase
62
Breakdown enzyme of noradrenaline?
MAO-A | COMT
63
Breakdown product of noradrenaline?
3-methoxy-4-hydroxyphenylglycol (MHPG) | Vanillyl mandelic acid (VMA)
64
What is the major metabolite of noradrenaline in the CNS?
MHPG
65
What is the major metabolite if noradrenaline in the endocrine/peripheral nervous system?
VMA
66
How is noradrenaline re-uptaked?
Noradrenaline reuptake channel
67
What drugs inhibit reuptake of noradrenaline?
Tricyclics | Reboxetine
68
Function of noradrenaline?
Arousal Anxiety Mood regulation Autonomic mediatino
69
Receptors for noradrenaline
Alpha 1, Alpha 2, Beta 1, Beta 2
70
Describe alpha 1 receptors for noradrenaline
Phospholipase C coupled | Mostly postsynaptic
71
Describe alpha2 receptors for noradrenaline
Gi-coupled | Mostly presynaptic autoreceptors
72
Describe beta receptors for noradrenaline
GS-coupled Predominate in locus cereulus Regulate arousal
73
Describe beta 1 receptors for noradrenaline
High affinity to noradrenaline
74
Describe beta 2 reeptors for noradrenaline
High affinity for epinephrine
75
Which noradrenaline receptor has high affinity for adrenaline?
Beta 2
76
Disorders in which low levels of noradrenaline is seen?
Depressin
77
Disorders in which abnormal levels of noradrenaline is seen?
Panic and anxiety disorders
78
Source of seretonin?
Tryptophan -> 5 hydroxy 1-trytophan -> seretonin
79
Rate limiting step of seretonin
Availability of tryptophan
80
Synthetic enzyme for seretonin
Tryptophan hydroxylase
81
Breakdown enzyme of seretonin
MAO-A
82
Break-down product of seretonin
5-hydroxyindoleaetic acid (5-HIAA)
83
What allows reuptake of seretonin?
Seretonin reuptake channel
84
What inhibits seretonin reuptake?
Tricycles | SSRIs
85
Function of seretonin
``` Mood Perception of pain Feeding Sleep-wake cycle Motor activity Sexual behaviour Temperature regulation ```
86
Receptors for seretonin
14 known subtypes
87
Which seretonin receptors are C-protein coupled?
All except 5 HT-3
88
Which seretonin receptor is in the gut?
5HT3
89
Describe 5HT1a receptors
Gi coupled postsynaptic. Antidepressant response. Sexual behaviour.
90
Describe 5HT1B receptors
Gi coupled presynaptic.
91
Describe 5HT1D receptors.
Gi coupled, both pre and postsynaptic.
92
Describe 5HT2 receptors
Phospholipase C coupled. Postsynaptic. Antagonism can lead to antipsychotic response (atypicals) and sedation.
93
Which seretonin receptor can be stimulated by LSD?
5HT2
94
Which seretonin receptor is downregulated after antidepressant or ECT treatment?
5HT2
95
Which seretonin receptor can lead to a response from atypical antipsychotics if antagonised?
5HT2
96
Which seretonin receptor is involved with regulation of circadian rhythym?
5HT7
97
Describe disorders related to low seretonin levels
Depression Aggression Suicide Impulsivity
98
How do seretonin levels have a role in psychosis?
Regulate dopamine system
99
Which medication is an agonist on 5HT1a?
Antidepressant
100
Which medication is a partial agonist on 5HT1a?
Anxiolytics
101
What action can 5HT1B receptor lead to?
Aggression
102
Which medication is an antagonist for 5HT1D?
Antimigraine
103
Which medication is an antagonist for 5HT2A?
Antipsychotic
104
Which medication is an agonist for 5HT2A?
Hallucinogens
105
Which seretonin receptor is involved in working memory, platelets and smooth muscle
5HT2A
106
Which receptor stimulation (seretonin) may result in cardiac valvular fibrosis
5HT2B - dexfenfluramine
107
What effect can stimulation of 5HT2C have?
Axiogenic and anorexic effect
108
What medication has an antagonistic effect on 5HT3?
Antiemetic
109
Which medication has an antagonistic effect on 5HT6?
Antipsychotic | Antidepressant
110
Which receptor helps as an antiemetic?
Anatogonist of 5HT3
111
Which seretonin receptor can act as antimigraine?
Antagonist to 5HT1D
112
What is DOPA decarboxylase involved in?
Synthesis of dopamine and seretonin.
113
How does DOPA decarboxylase form dopamine?
Tyrosine -> hydroxylation -> L-dopa -> catalyses by tyrosine hydroxylase -> DOPA decarboxylase decarboxylates L-DOPA to form dopamine.
114
Where is dopamine produced by the DOPA decarboxylase enzyme?
Basal ganglia | Sympathetic nervous system
115
What is dopamine the precursor of?
Catecholaminergic hormones, noradrenaline and adrenaline in adrenal medulla.
116
How does DOPA decarboxylase produce seretonin?
Tryptophan hydroxylase produces 5-PH tryptophan, which is decarboxylated by DOPA decarboxylase, forming seretonin.
117
Which type of enzyme is DOPA decarboxylase?
Homodimeric Pyridoxal Phosphate-dependent
118
Source of acetylcholine?
Choline and acetyl-coenzyme A
119
Rate limiting step of formation of acetylcholine?
Availability of choline
120
Synthetic enzyme for acetylcholine?
Choline acetyltransferase
121
Breakdown ezymes for acetylcholine?
Acetylcholinesterase - rapid
122
Breakdown product of acetylcholine?
Choline
123
Reuptake of acetylcholine?
None.
124
Function of acetylcholine?
``` Modulate arousal Learning Memory Rapid eye movement sleep Pain perception Thirst Parasympathetic mediation ```
125
acetylcholine receptors?
Muscarinic (M1 - M5) - G-protein coupled. | Nicotinic - ion channels.
126
Where are nicotinic, acetylcholine receptors more common?
Peripheral parasympathetic system
127
What do muscarinic acetylcholine receptors do?
Mediate attention
128
Disorders where there is reduced acetylcholine?
Alzheimers
129
How is acetylcholine involved in Parkinsons?
Involved in dopamine balance
130
Source of GABA
Glutamic acid
131
Rate limiting step for formation of GABA
Glutamic acid decarboxylase
132
Synthetic enzymes involved in formation of GABA?
Glutamic acid decarboxylase
133
Breakdown enzyme for GABA
GABA transaminase
134
Breakdown product of GABA?
Glutamate, then succinic acid
135
Reuptake of GABA?
Presynaptic nerve terminals Glial cells Uptake is bidirectional and temperature and ion-dependent.
136
What inhibits GABA reuptake?
Tiagabine
137
Function of GABA?
Mediates anxiety | Seizure cessation
138
In which medications is GABA involved in?
Benzo Barbituates EtOH
139
Receptors for GABA
GABAa and GABAb
140
Function of GABAa
Opens chloride channel, leading to hyperpolarization (inhibitory).
141
Structure of GABAa receptor?
5 subunits, at least 14 subunits.
142
Structure of GABAb receptor
G-protein coupled.
143
Selective agonist of GABAb receptor?
Baclofen
144
Disorders of GABA?
Anxiety disorders Alcoholism Epilepsy Huntington's
145
Source of glutamate?
1. 2-oxoglutarate and aspartate by aspartate aminotransferase or 2. glutamine by glutaminse or 3. 2-oxoglutarate by ornithine aminotransferase.
146
Regulation of gluamate?
Accummulation of precursors or end-product inhibition
147
Synthetic enzyme for gluamate?
Glutaminase
148
Breakdown enzymes for gluamate?
Glutamate dehydrogenase | Glutamine synthetase
149
Breakdown product of gluamate?
Glutamine or alpha-ketoglutarate
150
Reuptake of glutamate?
Glial with conversion to glutamine
151
Function of glutamate?
``` Metabolic: Intermediary in oxidation, ammonia cycle. Precursor of all GABA in CNS. NMDA - memory acquisition. Developmental plasticity. Epilepsy. Ischaemic brain injury. ```
152
Receptors of glutamate
Metabotropic - 8 in total, 3 groups. | Ionotropic - NMDA and non-NMDA.
153
Structure of metabotropic receptors for gluamate
Group I - mGluR1&mGluR5 are linked to phospholipase C.
154
Structure of NMDA glutamate receptor
Subunits with distinct binding sites for glutamate, glycine, phencyclidine, magnesium, zinc.
155
Structure of non-NMDA receptor for glutamate?
Kainate binding or AMPA type.
156
Which glutamate receptor mediates long term potentiation?
NMDA
157
Which disorders are linked to glutamate toxicity?
Stroke Schizophrenia Seizures
158
What can NMDA antagonists cause?
Hallucinations - PCP, ketamine
159
What is the primary inhibitory neurotransmitter in the spinal cord?
Glycine
160
How is glycine synthesized?
From serine by serine trans-hydroxymethylase and glycerate dehydrogenase
161
What are the rate-limiting steps of glycine production?
Serine trans-hydroxymethylase | Glycerate dehydrogenase
162
Function of glycine
Mandatory adjunctive neurotransmitter for glutamate receptors
163
What is the name of the excitatory glycine site on NMDA receptors?
Non-strychnine sensitive glycine receptor.
164
What is the Non-strychnine sensitive glycine receptor?
Inhibitory receptor.
165
Where is the Non-strychnine sensitive glycine receptor found?
Spinal cord
166
How are glycine and schizophrenia linked?
Facilitating glycine transmission can reduce negative symptoms.
167
What is the name of an experimental glycine reuptake inhibitor which is being trialled to reduce negative symptoms?
Bitopertin
168
Name two endogenous cannabinoid substances
Anandamide - a weak ligand | Arachnidonylglycerl - strong ligand
169
How are anandamide and Arachnidonylglycerl formed?
Arachidonic acid and ethanolamine
170
What are the cannabinoid receptors?
Central - CB1 | Peripheral - CB2
171
What do both cannabinoid receptors bind?
Tetrahydrocannabinol - active ingredient of maraijuana.
172
Functino of anadamide?
Lowers intraocular pressure Decreases activity level Relieves pain
173
What are neurotrophins?
Substances that act as polypeptide growth factors influencing proliferation and differentiation of neurons and glial cells.
174
Well-known neurotrophins?
Nerve growth factor Brain derived neurotrophic factor Neutotrophin 3 and 4
175
What is the neurotrophin hypothesis?
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
Which neurotrophin is involved in long-term potentiation of memory?
Brain derived neurotrophic factor
177
Which medications affect brain derived neurotrophic factor?
SSRI and ECT upregulate it.
178
Which mutation causes reduced brain derived neurotrophic factor activity?
Single nucleotide polymorphism in BDNF gene on chromosone 11p13 results in aa substitune of valine with methionine at codon 66.
179
What do humans with the 11p13 BDNF mutation have?
Impaired hippocampal activation and performance
180
What is reduced to a greater extent in patients with hallucinations in Lewy body compared to those without?
Corticol choline acetyl transferase
181
What can chronic antidepressant use lead to?
Induces a reduction in beta adrenoreceptor density around 2 weeks after treatment.
182
What is Kapur's aberrant salience theory?
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
Implications for psychosis in aberrant salience theory?
In psychosis where this is high dopamine in mesolimbic system, insignificant events and perceptions receive inappropriate significance, resulting in delusions.
184
What are the clinical implications of the aberrant salience theory?
Antipsychotics dampen the significance of abnormal experiences, but do not erase symptoms - they provide the platform for psychological resolution.
185
Where is an increase in 5HT2A receptors most prominent in those with depression?
Dorsolateral prefrontal cortex | Platelets
186
Effect of longterm antidepressant use on seretonin receptors
Reduce 5HT2 receptors | Increase 5HT1A function

MRCPsych Part A (22 decks)

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