NEUROCHEMISTRY Flashcards
what happens to neurotransmitter in Presynaptic neuron
It synthesises, transports and stores neurotransmitter
- synthesis - in cell body/soma
- stored in synaptic vesicle
- released through membrane fusion and exocystosis
Where does neurotransmitter go when released?
- Post-synaptic neuronal membrane
- presynaptic neuronal membrane auto-receptors for feedback
Neurotransmitter action is stopped by
- re-uptake back to pre-synaptic neuron eg monoamine transporters
- enzymatic breakdown eg MOA-A enzyme
- removed by glia or plasma circulation
Monoamines
dopamine
noradrenaline
adrenaline
seretonin
actetylcholine
histamine
Amino acids
GABA
Glutamate
Glycine
Classification receptors
1. ligand gated
2. metabotropic
3. ligand dependent/ nucelar receptors
Ligand gated (ionotropic) - binding alters the probability of opening a transmembrane pore, NMDA, GABA a and 5HT3, inhibitory CL-, excitatory Ca2+ (FAST EFFECT)
Metabotropic receptor proteins coupled to intracellular G proteins as transducers
SLOW EFFECT, pass membrane 7 times
Cyclase mediated 2nd messenger, GTP, ATP
Nuclear receptors = glucocorticoid receptors, cycsteine-rich DNA binding domain + ligand binding. Becomes transcription factor + binds to DNA via zinc fingers
e.g. progesterone, androgren
Dopamine
Source
Rate limiting step
Breakdown enzymes
Re-uptake
Function
Receptors
Disorders
Source - Tyrosine –> L dopa –> dopamine
Rate limiting step - tyrosine hydroxylase
Breakdown enzymes - Monoamie oxidase (MOA) and Catechol-o-methyl transferase (COMT)
Re-uptake - Dopamine transporter
Function - Motivation novelty seeking reward circuit, arousal and motor movement basal ganglia
Receptors - D1 + D5 - stimulatory D2,3,4, are inhibitory
D4 = clozapine high affinity
Disorders - low levels in parkinsons, high in psychosis in meso-limbic area
Seretonin
Source-
Rate limiting step
Breakdown enzymes
Re-uptake
Function
Receptors
Disorders
Source - tryptophan –> 5HT –> seretonin
Rate limiting step - tryptophan
Breakdown enzymes - MOA (A)
Re-uptake -seretonin re-uptake channels (TCA + SSRI inhibit)
Function - mood, pain, feeding, sleep-wake, sexual behaviour, temperature
Receptors - 5HT - all except 5HT3 are G protein (5hT3 = in gut)
Disorders= low Seretonin depression, Suicidie, aggression
Acetylcholine
Source
Rate limiting step
Breakdown enzymes
Re-uptake
Function
Receptors
Disorders
Source - choline and acetyl-coenzyme A
Rate limiting step- choline
Breakdown enzymes - acetylcholinesterase
Re-uptake - no re-uptake
Function - modulate arousal, learning, memory, REM sleep, thirst, parasympathetic
Receptors - muscarnin, nictinic
Disorders- reduced cholinergic function in alzheimers disease
GABA
Source
Rate limiting step
Breakdown enzymes
Re-uptake
Function
Receptors
Disorders
Source - glutamic acid (gluamate)
Rate limiting step - glutamic acid deocarboxylase
Breakdown enzymes - glutamic acid deocarboxylase
Re-uptake - presynaptic nerve terminals, surrounding glial cells
Function - mediates anxiety
Receptors - GABA A, GABA B
Disorders - Role in anxiety and alcoholism
Glutamate
Source-
Rate limiting step -
Breakdown enzymes
Re-uptake
Function
Receptors
Disorders
Source - oxo-glutatate and aspartate
Rate limiting step - accumulation of cursors
Breakdown enzymes - glutamate dehydrogenase
Re-uptake - largely glial
Function - metabolic role NMDA memory acquisition, ammonia cycle
Receptors - Metatropic and Ionotropic (NMDA)
Disorders - seizures, stroke, schizophrenia,
BDNF- Brain derived neurotrophic factor
IS a neurotrophin
may affect memory
Chronic stress reduces BDNF, has trophic effects on seretonin and nordranergic neurones
SSRI + ECT increase BDNF
Noradrenaline
Source
Rate limiting step
Breakdown enzymes
Re-uptake
Function
Receptors
Disorders
Source- tyrosine –> L dopa – dopaine –> noradrenaline
Rate limiting step - tyrosine hydroxylase
Breakdown enzymes - Monoamine oxidate A + Catechol-methyl transferase (COMT)
Re-uptake - Nordarenaline re-uptake channels
Function -Arousal, anxiety, mood regulation, autonomic mediation
Receptors - A and B
B1- high affinity to noradrenelaine , b2 high affinity to adrenaline
Disorders - Low levels in depression