Neurochemistry Flashcards
Where does neurotransmitter synthesis occur?
In the presynaptic cell body / soma - it is then transported to the presynaptic knob via axonal transport
It is stored in vesicles here then released into the synapse through vesicle exocytosis
What does lock and key refer to with neurotransmitter binding?
That there is only one chemical conformation that a neurotransmitter can bind at a receptor site (note one neurotransmitter may bind to different receptor types/locations however at each site only one chemical conformation is allowed)
After being released into the synapse how does cessation of neurotransmitter action occur?
- Reuptake back to the presynaptic neuron via special transporters (monoamine transporters)
- Break down by enzymes (COMT or MAO-A)
- Removed by glia or plasma circulation (e.g. glutamate shuffle)
Name some ways that feedback of neurotransmitters is elicited?
- Presynaptic control of synthesis
- Regulation of release
- Blockade.regulation of reuptake
- Autoreceptor (presynaptic receptor) blockade preventing release
- Inhibition of release via postsynaptic receptors (different route)
Name amino acids that are also neurotransmitters?
GABA
Glutamate
Glycine
What neurotransmitters are classified as peptides?
Endorphins
Cholecystokinin
Neurotensin
Neuropeptide Y
Leptin
Ghrelin
Outline the three types of receptors and some examples associated with them?
Ionotopic - ligand gated channels. Neurotransmitter binding affects the likelihood of opening a transmembrane pore/channel:
- Fast responses but often short lived
- Examples are GABA-A, 5-HT3, NMDA
- Inhibitory neurotransmitter - Cl- enters cell or excitatory Ca2+ enter the cell
Metabotropic receptors are G-protein coupled. Binding here affects protein synthesis within the cell through 2nd messenger cyclase mediated activation (GTP, ATP). G-proteins can be stimulatory (Gs) or inhibitory (Gi). Some G-proteins activate phospholipase C. Examples include DA, 5-HT receptors.
Nuclear receptors. Have a cysteine rich DNA-binding domain, a ligand binding domain and an amino ternminal region. As the ligand binds the receptor becomes a transcripton factorr and binds to DNA via zinc fingers. Examples include glucocorticoid receptors, progesterone, androgen, Vitamin D, Triidothyronine. GR receptor in cytoplasm and moves to nucleus when bound, T3 and oestrogen remain in nucleus and bind hormones directly to the nucleus.
How is Dopamine made by which enzyme and how is it broken down?
Tyrosine –> L-Dopa –> Dopamine
Enzyme: Tyrosine hydroxylase
Broken down by MAO-A and MAO-B and Catechol-o-methyl transferase (COMT)
- MAO-B has more selective activity for DA whereas MAO-A has more activity for Serotonin and Noradrenaline
What is homovanillic acid?
The breakdown product of dopamine
What does cocaine inhibit?
Reuptake via the dopamine transporter
What are D1 like and D2 like receptors?
Dopamine receptors are all G-coupled receptors
D1 like receptors include D1 and D5:
- These receptors are Gs therefore stimulate adenylate cyclase. D5 in limbic distribution - 10 x higher dopamine activity. D1 is only found on the post synaptic area and cannot be antagonised.
D2 like receptors include D2, D3, D4:
- Clozapine has a high affinity for D4 but selective D4 antagonist don’t work as antipyschotics. D4 is mostly found in the frontal cortex of the brain.
How is noradrenaline made?
Tyrosine –> L-Dopa –> Dopamine –> Noradrenaline –> Adrenaline
As for dopamine tyrosine hydroxylase is the rate limiting step
Dopamine-b-hydroxylase converts dopamine to noradrenaline
Phenylethanolamine-N-methyltransferase then converts noradrenaline to adrenaline
Which enzymes break Noradrenaline down?
MAO-B and COMT
What is noradrenaline broken down to?
MHPG and VMA
- 3-methoxy-4-hydroxyphenylglycol (centrally)
- Vanillyl mandelic acid (peripherally/endocrine system)
What are the Noradrenaline receptors?
alpha-1: post synaptic and phospholipase C coupled
alpha-2: pre synaptic and are Gi coupled
Beta-1: high affinity for noradrenaline
Beta-2: high affinity for adrenaline
- Both types of Beta-receptor are Gs coupled and are found in high numbers in locus coerlus.
How is Serotonin made?
Tryptophan - 5-hydoxy L-trytophan –> serotonin
Rate limiting step is availability of Trptophan
Then synthetic enzyme involved is Tryptophan hydroxylase
What is 5-hydroxyindoleacetic acid (5-HIAA)
The breakdown product of serotonin
What is the only serotonin receptor not to be G-protein coupled?
5-HT3 - ligand gated (ionotropic) found in abundance in the gut and associated with motility (responsible from sickness of SSRI)Outlin
Outline the location and function associated with the following receptors?
a) 5-HT1A
b) 5-HT1B
c) 5-HT1D
d) 5-HT2A
e) 5-HT2B
f) 5-HT2C
g) 5-HT3
h) 5-HT6
i) 5-HT7
a) postsynaptic, Gi, anti-D (agonise), anxiolytics (partial agonise). associated with an anti-D response and sexual behaviour
b) presynaptic, Gi, implicated in aggression behaviour
c) pre + postsynaptic, Gi, antagonism is beneficial for antimigraines
d) 5-HT2A phospholipase C. Psychedelics lead to agonism/partial agonism. Antipsychotics antagonise. Function useful in working memory. Expressed in platelets and smooth muscle
e) 5-HT2B stimulation may cause cardiac valvular fibrosis (dexfenfluramine)
f) 5-HT2C agonism leads to anxiogenic and anorexic effects
g) 5-HT3 antagonism leads to antiemetic effects
f) 5-HT6 are implicated in anti-depressants and antipsychotics
g) 5-HT7 is involved in the regulation of circadian rhythms
What is DDC and which neurotransmitters is it implicated in?
DOPA decarboxylase (DDC) is an enzyme:
It converts L-DOPA to dopamine through decarboxylation
It converts 5-OH tryptophan to Serotonin
