NT metabolism Flashcards
A purinergic synapse is made up of two molecules
ATP and adensoine
Receptors of ATP
P2Y and P2X
Which enzyme is responsible for the hydrolysis of ATP into Adesnosine
ectodiphosphohydrolase/ ecto 5’ nucleotidsse
example of 1 datty acid and phosphate molecule
phosphotidylserine
Define lipid raft
cholesterol rich patches of cell membrane forming a distinct microenvironment that can cluster receptors for faster dimmerization eg FGF receptors
Name the cholesterol derivatives form THC Prostaglandin Anandamide Cholesterol
Cortisol
estradiol
testosterone
Vitamin D3
How does endocannabinoid signalling work?
Endocannabinoids are synthesized upon demand. trigger signal : calcium elevation or mGluR activation. ECs act as retrograde messengers, suppressing presynaptic release of inhibitory NTs
Arachidonic acid annd glycerol lead to
acetylCoA
Purinergic receptors for
adenosine
ATP, UTP
P1 gprotein coupled
P2x ligand gated and P2Y G protein coupled
How is anandamide metabolised
Degenerated by Fatty Acid amide hydrolase to arachidonic acid and ethanolamine
Otto loewi’s experiment on vagusstoff was which NT
ACh
What is depolarization induced supression of inhibition
when endocannabinoids are activated by calcium elevvation or activation of metabotropic glutamate receptors, depolarization induced supression of inhibition occurs. Ca and mGluR act as retrograde messengers to supress synaptic release
Classify the NTs Glutamine, GABA, Glycine ACh, NE, DA, Histamine 5HT Substance P, enkephalins, somatostatin, neuropeptide Y 2AG, anandamide
Glutamine, GABA, Glycine- amino acids
ACh, NE, DA, Histamine 5HT-amines
Substance P, enkephalins, somatostatin, NEUROPEPTIDE y-peptides
2AG, anandamide- endocannabinoids
In vesicular transport glutamate and GABA depend on which gradients?
Glutamate is -vely charged, makes it easier to exchange a H+, electrochemical gradient greater than pH gradient
GABA depends on both pH and electro because it’s a Zwitter ion
ACh is +vely charged, more on pH than electrochemical
Role of AISIC channels in the hippocampus interneurons
They are activated by protons, hence activate inhibition if excitation, causing termination of seizures,Low pH mediates a cationic current, leading to depolarization
Consequence of impaired acidification
Decreased amplitude in the post synapse hence cortical spread in depolarization
2 ways of glutamate synthesis
Glutamine (PAG)-glutamic acid-(decarboxylase)GABA-
alphaketoglutarate through glu-aminotransferase to glutamate
Energy of vGlut transporter provided by
electrochemical gradient more than pH gradient
Name 2 EAAT transporters and what is the main gradient
EAAT is a PM transporter for clearance. Uses sodium gradient, counter transports potassium. Transports glutamate and cleaves it, fast binding to Glu to reduce Glu transiently.
EAAT1 and 2-glia main glu transporter in hippocampus
EAAT 3-neurons
recycling of glutamate
Glutamine synthetase in astrocytes converts glutamate to glutamine. Glu is excitatory so only glutamine will be taken up by astrocytes because it’s not neuroactive. Then at presynapse, glutamine is converted to glutamate by glutaminase
Loading of GABA vesicles is by
vGAT, which has low substrate affinity
Transport of GABA and glycine is by
VIAAT. using a proton gradient produced by vesicular ATPase/
Generation of GABA
alpha ketoglutarate-GABAT-glutamate-Glutamic acid decarboxylase-Gamma ammino butyric acid
Role of GAT 1
GAT-1 regulates tonic GABA-R mediated inhibition. Inactivates GABA for reuptake by the pre-synapse
GHB is
Gamma hydroxybutiric acid, derivative of GABA, GABA B receptor agonist
How is glycine cleared from the synaptic cleft
GLY T1 and GLY2 remove glycine from the synaptic cleft
How is glycine produced
from serine via serin hydroxymethyltransferase at the MT
How is acetylcholine generated?
Acetylcoenzyme A+choline via choline acetyltransferase
How is acetylcholine broken down into choline and acetate
acetylcholine esterase inactivates ACh
Between vACht and Vmonoamine transporters, which one has greater velocity?
VMATs have greater velocity and higher binding affinity becasue of substrate cytotoxicity
How are ACh vesicles loaded?
Via vesicular ACh transporter which has a higher pH gradient compared to electrochemical gradient because ACh is +vely charged. vACh has low binding affinity and is slow due to high intracellular conc of ACh.
Drugs that interfere with ACh
vesamicol inhibits vACH transporter
Curare and mecamylamine are nicotinic antagonist blocks, block nicotinic ACh receptors
Botulinus and Tetanus- inhibit ACh release (vesicular release and docking)
Spider toxin stimulates release
Name 2 muscarinic agonists
atropine
benzatropine
2 mechanisms of ACh inactivation mechanims
diffusion out of cleft
Acetylcholinesterase enzymatic degradation
True/false. Nicotinergic/ionergic transmission is rare in CNS
True. More nicotinic receprors in muscular endplate
DA, NE and epinephrine are exmples of
catecholamines
seratonin is derived from which aa
tryptophan
how is DA derived
L-tyrosine- tyrosine hydroxylase-L-DOPA-DOPA decarboxylase-Dopamine
how is norepinephrine derived
dopamine-dopamine hydroxylase-NE-Nmethyltransferase-Epinephrine
Catecholamine vesicular transporter
vesicular monoamine transporter VMAT, Mg dependent
Neuronal catecholamine transporter
DA transporter
NE transporter use sodium /potassium ATPase
Inactivation of catecholamines
monoamine oxidase, catechol-0-methyltransferase
Most antipsychotic drugs block which receptors of DA
D2
Seratonin production
tryptophan- tryptophan hydroxylase- 5HTP-l aromatic acid decarboxylase- 5HT/seratonin
