Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

NEUR1005 > Neurotransmitter systems and neurochemistry (Prof. Sihra) > Flashcards

Neurotransmitter systems and neurochemistry (Prof. Sihra) Flashcards

1
Q

What are the criteria for a molecule to be a neurotransmitter (NT) ?

A
  • synthesis/presence in the nerve terminal
  • storage in nerve terminal in secretory vesicles
  • release (regulated by Ca2+)
  • postsynaptic effect which is mimicked by exogenous ligands
  • inactivation by specific mechanisms: reuptake + catabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the classical NT types ?

A
  • AAs: Glu, GABA, GLy
  • derivative of AAs: dopamine (DA), noradrenaline (NA/NE), 5-hydroxytryptonamine (5-HT), histamine
  • hetero-oligomers of AAs i.e. peptides: opioids peptides,, endomorphins, nociceptin, neurotrophin
  • the “prototypic” NT = ACh
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the non-canonical NT types ?

A
  • nucleotides and nucleosides (ATP, adenosine)
  • lipid derivatives: endocannabinoids
  • gases (NO, CO)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the major excitatory NT in the CNS ?

How is this NT synthesized and taken up after release ?

A

Glutamate
Gln is converted to Glu by glutaminase. Part of it is taken up in the terminal by the EAAT1 (Excitatory AA Transporter 1) / Glu transporter, or taken up by astrocytes (glial cella) via GLAST (Glu Asp transporter) that converts it to Gln and delivers it to the terminal via SN1 (Gln transporter).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is EAAT1 ?

A

EAAT1 is a protein that mediates the transport of glutamic and aspartic acid back in the nerve terminal with the cotransport of three Na+ and one H+ cations and counter transport of one K+ cation. This co-transport coupling (or symport) allows the transport of glutamate into cells against a concentration gradient.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are GLAST and GLT-1 ?

A

GLT-1 and GLAST astroglial transporters are the glutamate transporters mainly involved in maintaining physiological extracellular glutamate concentrations. They use co-transport coupling like EAAT1.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the major inhibitory NT in the CNS ?

A

Gamma-aminobutyric acid (GABA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How are Glu and GABA produced ?

A

Alpha-ketoglutarate leaves the Krebs cycle, can be converted to Glu by GABA-T (GABA transaminase), which can then be converted to GABA by GAD (Glutamate decarboxylase).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Hiw is Glu stored in small synaptic vesicles (SSVs) ?

A

A proton pump created a electrical gradient py pumping protons H+ into the SSVs (hydrolysis of ATP). The negative charge of Glu drives it inside the positive vesicle.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is vGLUT1/2 ?

A

Vesicular glutamate transporter 1 (VGLUT1) is a vesicle-bound protein. It is a sodium-dependent phosphate transporter that is preferentially associated with the membranes of synaptic vesicles and functions in Glu uptake into vesicles.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is vGAT ?

A

The vesicular GABA transporter VGAT is responsible for uptake and storage of GABA and glycine by synaptic vesicles in the CNS. It is different from the plasma membrane transporters in that it is driven by a proton electrochemical gradient across the vesicle membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is GLYT1-2 ?

A

Sodium- and chloride-dependent glycine transporter. It brings Gly back from the cleft into the nerve terminal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Can our body made ACh alone ?

A

No, choline is required in the diet.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How is ACh made ?

A

An acetyl group associates w/ CoA to form Acetyl CoA. This associates w/ choline (form the diet) and is converted to ACh via choline acetyltransferase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How is ACh inactivated/broken down ?

Why is this break inactivation easy ?

A

By very active acetylcholinesterases (also plasma pseudocholinesterases).
As an ester, ACh is relatively labile and susceptible to esterase mediated hydrolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What part of ACh is recycled ?

A

Choline is recycled by reuptake.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is VAChT ?

A

The Vesicular acetylcholine transporter (VAChT) is a NT transporter which is responsible for loading ACh) into secretory organelles in neurons making ACh available for secretion.
It is co-packaged w/ ATP.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the effect of He. (Hemicholinium) ?

A

He. is a drug which blocks the reuptake of choline by the high-affinity choline transporter (ChT) at the pre synapse –> rate limiting step in synthesis of ACh –> He. = indirect ACh antagonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the effect of Ve. (Vesamicol) ?

A

Vesamicol is an experimental drug, acting presynaptically by inhibiting acetylcholine (ACh) uptake into synaptic vesicles, thus reducing its release.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the fct of ChT ?

A

The high-affinity choline transporter (ChT) (also known as solute carrier family 5 member 7) is a cell membrane transporter and carries choline into acetylcholine-synthesizing neurons (by using Na+ gradient).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the characteristic of the synaptic vesicle ATP dependent proton pump ?

A

It is conserved in virtually all organisms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

From which AAs are catecholamines derived ?

A

Tyrosine

23
Q

What are the steps leading from tyrosine to adrenaline (ADR) ?

A

Tyrosine –> L-DOPA (dihydroxyphenylalanine) by tyrosine hydroxylase (TH).
L-DOPA –> dopamine (DA) by L-aromatic AA decarboxylase (AADC)
DA –> noradrenaline (NA) by dopamine-beta-hydroxylase DBH)
NA –> ADR by phenylalanine-N-methyltransferase (PNMT)

24
Q

How are catecholamines stored into large dense core vesicles (LDCVs) ?

A

By the vesicular monoamine transporter 2 (VMAT2) (also known as solute carrier family 18 member 2 (SLC18A2)). This is an integral membrane protein that transports monoamines.

25
Q

Is it the electrical gradient or the pH gradient that allows VMAT2 to fct ?
Why ?

A

It is the pH gradient, because when protons are pumped into the LDCVs, Cl- ions often follow, rendering the H+ charge neutral. Instead, VMAT exchanges monoamines against protons.

26
Q

Are monoamines packaged in the LDCVs on their own ?

A

No, they are co-packaged w/ proteins.

27
Q

What drugs can act on VMAT2 ?

A

Methamphetamine, dextroamphetamine, methylphenidate, and lobeline block VMAT2, inducing monoamine release in the cytosol –> non exocytotic NT release

28
Q

How is DA recycled by the pre-synaptic neuron ?

A

The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps DA out of the synapse back into the cytosol.

29
Q

How is NA recycled by the pre-synaptic neuron ?

A 
Via NET (Norepinephrine Transporter) = monoamine transporter, responsible for the sodium-chloride (Na+/Cl−)-dependent reuptake of extracellular NA/NE
NET can also reuptake extracellular DA
30
Q

Which drugs can act on DAT and NET ?

A

Dextroamphetamine, methylphenidate, reboxetine (NRI), venlafaxine (SNRI).

31
Q

Form which AA are indoleamines derived from ?

A

Tryptophan

32
Q

What are the steps between Trp and melatonin ?

A

Tryptophan –> 5-hydroxytryptophan by tryptophan hydroxylase (TPH) - blcoked irremissibly by parachlorophenyalanine
5-hydroxytrytophan –> 5-hydroxytryptamine (5-HT/serotonin) by L-aromatic AAD
In the PINEAL GLAND ONLY:
5-HT –> melatonin by 5-hydroxyindole-O-methyltransferase

33
Q

What is the only imidazole amine NT ?

From which AA is it derived ?

A

Imidazole amine NT = histamine, derived from hystidine via histidine decarboxylase

34
Q

What is pro-opimelanocortin (POMC) ?

A
  • POMC = a precursor polypeptide w/ 241 AAs
  • synthesized in the pituitary from the 285-amino-acid-long polypeptide precursor pre-POMC, by the removal of a 44-amino-acid-long signal peptide sequence during translation
35
Q

What is the function of POMC ?

A

POMC –> cleaved to give rise to multiple peptide hormones, packaged in LDCVs in response to appropriate stimulation:

  • α-MSH produced by neurons in the arcuate nucleus has important roles in the regulation of appetite and sexual behavior, while α-MSH secreted from the intermediate lobe of the pituitary regulates the production of melanin
  • ACTH = a peptide hormone that regulates the secretion of glucocorticoids from the adrenal cortex
  • β-Endorphin and [Met]enkephalin are endogenous opioid peptides with widespread actions in the brain
36
Q

What do we mean when we talk about cotransmission ?

A

To the fact that, in various local sites around the body, small molecules are “cotransmitted” w/ a neuropeptide.

37
Q

Give a few examples of cotransmission.

A
  • norepinephrine cotransmitted w/ neuropeptide Y (NPY) in the locus ceruleus neurons + the sympathetic preganglionic neurons
  • DA w/ neurotensin or cholecystokinin in substantia nigra neurons
  • 5-HT w/ TRH, substance P or enkephalin in raphe nuclei neurons
  • GABA w/ enkephalin in striatal neurons projecting to globus palllidus
38
Q

What is the particularity of small gas molecules and endocannabinoids when they act as NTs ?

A

They exert retrograde transmission.

39
Q

How many types of synaptic vesicles are there ?

How do they differ ?

A
  • type 1: SSVs, 50nm diameter, GABA, Gly + Glu, recruitment + localisation to Active Zones, fast phasic release + recycling
  • type 2: LDCVs, 250nm diameter for monoamines + SDVs (smaller diameter for 5-HT), delocalized organisation, slow tonic release, ER/Golgi replenishment
  • type 3: LDCVs (250nm diameter), neuropeptides, otherwise same as type 2
40
Q

What are the 5 steps of neurotransmission ?

A
  1. AP propagation down the axon (v-gated ion channels)
  2. Ca2+ entry into synaptic knob
  3. Release of NT by exocytosis
  4. Binding of NT to postsynaptic receptors
  5. Opening of specific ion channels in sub synaptic membrane
41
Q

What are P/Q type calcium channels ?

A

High-voltage-gated calcium channels contributing to vesicle fusion and NT release at synaptic terminals, present in Purkinje (P = Purkinje) neurons in the cerebellum and in cerebellar granule cells.

42
Q

What are N type calcium channels ?

A

High-voltage-gated calcium channels contributing to vesicle fusion and NT release at synaptic terminals, present throughout th brain and spinal chord (N =neural).

43
Q

What is the role of synaptotagmin ?

A

Synaptotagmin 1 (or synaptotagmin) = a Ca2+ sensor in the membrane of the pre-synaptic axon terminal.

44
Q

What is the role of dynamin ?

A

Dynamin = a GTPase responsible for endocytosis in the eukaryotic cell –> it is involved in the scission of newly formed vesicles from the membrane of one cellular compartment and their targeting to, and fusion with, another compartment, both at the cell surface (presynaptic membrane) as well as at the Golgi apparatus.

45
Q

How does dynamic work (theoretically) ?

A

Dynamin forms a helix around the neck of a nascent vesicle. Cooperative GTP hydrolysis results in the lengthwise extension of this helix, breaking the vesicle neck.

46
Q

What are the mane proteins that mediate vesicle fusion ?

A

The SNARE proteins.

47
Q

How was N-ethylmaleimide Sensitive Factor (NSF) discovered ?

A

NSF was discovered by James Rothman and colleagues in 1987 while at Stanford University; they identified NSF after observing that a cytoplasmic factor, required for membrane fusions, was inactivated by treatment with N-ethylmaleimide. This assay enabled them to purify NSF.

48
Q

What is SNAP 25 ?

A

Synaptosomal-associated protein 25 or Solube NSF Attachment Protein (SNAP-25) = a t-SNARE protein, a component of the trans-SNARE complex
SNAP25 is proposed to account for the specificity of membrane fusion

49
Q

What are SNAREs ?

A

SNARE proteins (“SNAP (Soluble NSF Attachment Protein) REceptor”) are a large protein superfamily consisting of at least 24 members in yeasts and more than 60 members in mammalian cells. Their primary role is to mediate vesicle fusion.

50
Q

What are syntaxins ?

A

Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis.

51
Q

What are synaptobrevins ?

A

Synaptobrevins (synaptobrevin isotypes 1-2) are small integral membrane v-SNARE proteins with molecular weight of 18 kDa that are part of the vesicle-associated membrane protein (VAMP) family.

52
Q

How does G-alpha mediated signaling in 7TM receptors work ?

A

It involves the generation of “soluble” 2nd mesengers.

53
Q

What effects do G-alpha s/i and G-alpha q have ?

A

G-alpha s/i can stimulate or inhibit adenylate cyclase, thus leading to greater or lower levels of cAMP
G-alpha q stimulates PLC which leads to the production of IP3 and diacylglycerol
BOTH 2nd messengers lead to phosphorylation dependent (or independent) modulation of targets and ultimately to facilitation of synaptic transmission

54
Q

How does G-beta gamma signaling work for 7TM receptors ?

What effect does this have on synaptic transmission ?

A

It involves membrane delimited interaction w/ plasma membrane resident proteins i.e. ion channels and t-SNAREs.
This ultimately leads to inhibition of synaptic transmission.

NEUR1005 (31 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions