Principles of CNS Biochemistry Flashcards
What is synaptic neurotransmission?
The release of neurotransmitters into the synaptic cleft which can induce an inhibitory or excitatory effect on post-synaptic receptors
What are neurotransmitters?
Neurotransmitters are chemicals used for neuron communication in the synapatic cleft.
What are the types of neurotransmitters?
Neurotransmitters are divided into small neurotransmitters and neuropeptides.
What are small neurotransmitters?
Small neurotransmitters are synthesised in the presynpatic terminal and packaged in clear small vesicles. They modulate fast synaptic transmission
Where are small neurotransmitters synthesised?
In the presynaptic terminal
Where are the enzymes that metabolise small neurotransmitters synthesised?
In the soma
What are peptide neurotransmitters?
Short chain polypeptides which are stored as large vesicles in the presynaptic neuron. It is synthesised along with the enzyme metabolisers in the soma and transported down the axon. They modulate ongoing synapatic activity and slow synaptic transmission.
Which receptors do neuropeptides act on?
G protein-coupled receptors which are metabotropic and induces secondary messanger response.
Which physiological processes are neuropeptides involved in?
Secretion of salivary fluid, gastric fluid, intestinal fluid and electrolytes.
How are neuropeptides synthesised?
In the soma from precursor proteins through selective cleavage by enzymes
Which pathologies are associated with neurotransmitter function?
Alzheimer’s disease, Parkinson’s disease, Schizophrenia and Depression.
What are the classes of small neurotransmitters?
Biogenic amines, small amines and gases and aCH
What are the biogenic amines?
Catecholamines, serotonin and histamine.
What are the amino acid neurotransmitters?
Glutamate, GABA and glycine.
What are the gas neurotransmitters?
NO and CO. These are synthesised and released immediately following action potential and are not stored in vesicles so they are not released by exocytosis.
What are examples of large neuropeptides?
Substance P, endorphins, somatostatin and vasopressin.
What is co-transmission?
The exocytosis of multiple separate vesicles due to the frequency of stimulation. Low frequency means there is multiple exocytosis of small vesicles. High frequency has multiple exocytosis of small and large vesicles.
What is co-release?
The release of a vesicle containing more than one type of neurotransmitter.
What is the criteria for chemical messenger to be a neurotransmitter?
It must be synthesised or present in the neuron. It must produce a response when bound to receptors on target cell l to continue the signal. It should have the same response when attached directly to the target cell. It must be removed from synaptic cleft.
What is a catecholaminergic neuron?
A neuron which releases dopamine, adrenaline or noradrenaline.
Which receptors do neurotransmitters of the nervous system act on?
Ionotropic and metabatatropic.
What are ionotropic receptors?
They are ligand gated ion channels composed of multiple subunits which open in response to ligand binding on allosteric site and allow influx of ions which cause a change in the membrane potential and generates a response
What are metabotropic receptors?
G protein coupled receptors which respond to binding of neurotransmitter by activating G protein to induce second messanger activation or activate an ion channel.
What type of receptor is muscarinic?
Metabotropic/ G protein coupled cholinergic receptor associated mainly with the parasympathetic nervous system and found in the peripheral tissues of glands and smooth muscles.
What type of receptor is nicotninic receptor?
Ionotropic/ligand gated ion channel cholinergic receptor associated with the sympathetic and parasympathetic nervous system
What is acetylcholine?
A small neurotransmitter important in the cerebral cortex and the hippocampus for modulating fast-synapatic transmission by co-ordinating neuronal firing and synaptic plasticity.
What are sweat glands?
Muscarinic metabatropic receptors part of the sympathetic nervous system.
What system is the muscarininc receptor involved in?
Muscarinic receptor which acts on peripheral tissues and glands and is involved mainly in the parasympathetic system. Muscarinic receptor are present in the sweat glands, intestines for gut motility, smooth muscle of the heart for relaxation and CNS.
Which sympathetic response is muscarininc receptor invovled in?
The only sympathetic Muscarinic receptor are present in the sweat gland for secretion.
Which division of the autonomic nervous system are nicotinic receptors involved in?
Nicotininc receptor are involved in the sympathetic and parasympathetic response. It is present in the neuromuscular junction, sympathetic chain ganglia, adrenal chromaffin cells and the parasympathetic postganglionic neurons.
What is Alzheimer’s disease and treatment?
Neurodegenerative disease with depletion of acetylcholine due to build up of protein deposits in the brain that forms plaque. This creates issues with the hippocampus and the cerebral cortex involved in memory and cholinergic innervation. There is depletion of glutamate
What is the prevalence of Alzheimer’s disease?
More prevalent in those over 80, with 20% total. 5% in those over 60.
How is acetycholine synthesised?
Choline + acetylcoA -> acetylcholine, catalysed by choline acetyltransferase (CHAT
How is acetylcholine metabolised?
Acetylcholine -> choline + acetic acid, catalysed by acetylcholinesterase.
Which drugs affect the acetylcholinesterase?
It is inhibited by pyridostigmine, in order to increase depleted levels of AcH associated with glaucoma, myasthenia gravis and Alzhiemer’s disease.
What are the types of nicotinic receptors?
Two types: Nictonic Nn and Nicotinic Nm
Where are Nicotinic Nn found?
In the post sympathetic ganglia and the presynaptic cholinergic memory. They mediate fast neurotransmission.
Where are Nicotinic Nm found?
In the skeletal motor end plate of the NMJ
What are the types of muscarinic receptors?
M1, M2, M3, M4, ,M5
Which muscarinic receptors are coupled to G protein/phospholipase C?
M1, M3 and M5 which induces the secondary messanger phospholipase C. M1 is found in the cortex, These are found in the brain and the heart.
Which muscarinic receptors are coupled to G protein-> open K+ ion channels?
M2 which is in the heart and and M4 which is found in the basal ganglial, hippocampus and thalamus.
What are the essential amino acid neurotransmitters derived from the diet?
Glutamate, glycine and GABA.
What is glutamate?
Amino acid excitatory neurotransmitter which is principal neurotransmitter of the brain.
How is glutamate synthesised?
From Glutamine -> GLutamate, catalysed by glutaminase enzyme. It can also be synthesised from transamination of 2-oxo-glutarate, a product of the TCA cycle.
How is glutamate metabolised?
.
Reuptake by pre-synaptic cell or taken up by peptide transporters into glial cells, where glutamate is converted ->glutamine by glutaminase enzyme