Acetycholine Synthesis, Storage Release Flashcards
Neurotransmitters
Answer with amine, peptide or amino acid
Acetylcholine
Amine
Neurotransmitters
Answer with amine, peptide or amino acid
Dopamine
Amine
Neurotransmitters
Answer with amine, peptide or amino acid
Norepinephrine
Amine
Neurotransmitters
Answer with amine, peptide or amino acid
Epinephrine
Amine
Neurotransmitters
Answer with amine, peptide or amino acid
Serotonin
Amine
Neurotransmitters
Answer with amine, peptide or amino acid
GABA
Amino acid
Neurotransmitters
Answer with amine, peptide or amino acid
Glutamic acid
Amino acid
Neurotransmitters
Answer with amine, peptide or amino acid
Glycine
Amino acid
Neurotransmitters
Answer with amine, peptide or amino acid
CCK
Peptide
Neurotransmitters
Answer with amine, peptide or amino acid
Neuropeptide Y
Peptide
Somatostatin is a neurotransmitter
T/F
T
Substance P is a neurotransmitter
T/F
T
Vasopressin is a neurotransmitter
T/F
T
Neurotransmitters
Answer with amine, peptide or amino acid
TRH
CRH
Peptide
Peptide
Neurotransmitters
Answer with amine, peptide or amino acid
Enkephalins
Endorphins
Peptide
Peptide
vasoactive intestinal peptide is not a neurotransmitter
T/F
F
Ach is responsible for ALL motor transmission in vertebrates
T/F
T
Ach mediates _____pathetic actions of the ANS
Parasympathetic
Both pre ganglionic fibers of sympathetic and parasympathetic nervous system are myelinated
T/F
T
Functions of Ach in the CNS
• Basal Forebrain:
-______________
-_____________
–_________ Disease
arousal and attention; Learning and memory
Alzheimer
Functions of Ach in the CNS
• Parabrachial nucleus
-__________
– (Stop or Continue?) to fire during REM
– # Cells correlate with REM sleep
REM sleep
Continue
Functions of Ach in the CNS
• striatum- ____________
•______ and other sensory input
Reward and Addiction
Pain
Functions of Ach in the PNS
• Vasculature (endothelial cells) – Release of _____________(____) and vaso______
• Eye iris (pupillae sphincter muscle) – (Contraction or Dilation ?) and _______
endothelium-derived relaxing factor ; NO
dilation
Contraction; miosis
Functions of Ach in the PNS
• Ciliary muscle – (Contraction or Dilatation?) and accommodation of lens to (far or near?) vision
• Salivary and lacrimal glands – Secretion is (thick or thin?) and (mucous or watery?)
Contraction
Near vision
Thin
Watery
Functions of Ach in the PNS
• Bronchi – (Constriction or Dilation?) , (increased or decreased?) secretions
• Heart – ___cardia, ___eased conduction (AV ___ at high doses), (positive or negative?) ____tropic action
Constriction
Increased
Brady; decreased; block ; negative inotropic
Functions of Ach in the PNS
• GIT – ____eased tone, ___eased secretions, (constriction or relaxation?) at sphincters
• Urinary bladder – (Contraction or Relaxation ?) of detrusor muscle, (Contraction or Relaxation ?) at sphincters
Incr; incr; relaxation
Contraction ; relaxation
Functions of Ach in the PNS
• Sweat glands – (excessive or diminished?) sweating.
• Reproductive tract, male – ______
Excessive
Erection
Diaphoresis = _________
sweating more than normal or you’re sweating for no clear reason.
Functions of Ach in the PNS
• Uterus – variable , depending on _________
hormonal influence
Ach at the NMJ
• Regulated release of Ach causes muscle ___polarization: _____ or ______
– (Contraction or Relaxation?) of muscle
De
mEPP or EPSP
Contraction
_______ + ______ = acetylcholine
_____ enzyme helps
Acetyl coA
Choline
Choline acetyltransferase
Acetylcholine is broken down to _____ and ———- by ____ enzyme
Acetate
Choline
Acetylcholine esterase
Acetyl coA is gotten from _____ with the help of _____
Pyruvate
PDH complex
Choline acetyltransferase is inhibited by __________
Mercurials
Acetylcholine esterase is inhibited by _______ agents eg _____
Nerve
Sarin
Choline is replenished by ______ or _____
Reputake
Diet
________ loads acetylcholine into a vesicle
Vesicular acetylcholine transporter
_______ loads choline back into the nerve or into the vesicle
High affinity Choline transporter
Ach Equilibrium
• (choline)+(Acetyl-CoA) ——> Ach + (CoA)
– Availability of choline (CHT) drives rxn to the (left or right?)
– Decrease in Ach will cause shift in equilibrium (no substrate for reverse rxn)
Right
Ach levels are extremely (stable or unstable?) over a wide range of neural activity
Stable
Ach Release
• Action potential arrives at _______ terminal, __polarizing the membrane
• _____ ionmust be present for Ach to be released and have any effect
pre-synaptic
de
Ca2+
Other Factors that Affect Ach Release
• Trophic factors
-NGF exerts (slow or rapid?) (short or long?) term effects on Ach synthesis and release
•________ (other hormones?)
Rapid; short
Estrogen
Estrogen decreases ChAT levels
T/F
F
Increases
Acetylcholinesterases
•_______ and ——- of acetylcholine
• Prevents ________ receptor
• Critical for recycling _____
Hydrolysis and deactivation
acetylcholine reactivating
choline
Acetylcholinesterases
• Limits ________ events/ _____
Receptor signaling ; duration
Acetylcholine esterases are Found in (intra or extra?) cellular space, ______
Extra ; synaptic cleft
Acetylcholine esterase is a marker of cholinergic cells
T/F
F
It is not
Inhibitors of AchE
–_______ disease
–_____,_______
_ Bioterrorism
Alzheimer
Glaucoma, myasthenia gravis
______ is a drug used to treat dementia of the Alzheimer’s variety
Aricept
Inhibition of storage of acetylcholine : ______
Vesamicol
Inhibition of release of ach could be by _______
Botulinum
Or
Aminoglycosides
ACETYLCHOLINE was the second neurotransmitter discovered
T/F
F
first
ACETYLCHOLINE:
- Was originally described as “ _______ stuff” by Otto Loewi because of its ability to ______________________________.
vagus
mimic the electrical stimulation of the vagus nerve
In the autonomic nervous system, acetylcholine (ACh) is the neurotransmitter in the preganglionic ______________________ neurons.
sympathetic and parasympathetic
In the autonomic nervous system, acetylcholine (ACh) is the neurotransmitter at all the ________pathetic innervated organs.
parasym
In the autonomic nervous system, acetylcholine (ACh) is the neurotransmitter in the following sympathetic ANS
The _________.
The _______ glands.
__________ muscle
adrenal medulla
sweat
Piloerector
In the peripheral nervous system, ACh is the neurotransmitter at the __________ junction between the ________ and ________.
neuromuscular
motor nerve and skeletal muscle
In the central nervous system, ACh is found primarily in ____________
• A few important long-axon cholinergic pathways have also been identified.
Noteworthy is the cholinergic projection from the ___________ of ________ (in the _____________) to the _________ ________ and associated limbic structures
interneurons
nucleus basalis of Meynert
basal forebrain
forebrain neocortex
Degeneration of this pathway between the nucleus basalis of Meynert to the forebrain neocortex is one of the pathologies associated with __________ disease.
Alzheimer’s
Acetylcholine is synthesized in nerve terminals from _____________ and __________.
Acetylation is through the help of ATP in a reaction catalyzed by _____________ present in the axoplasm.
acetyl coenzyme A
choline
choline acetyltransferase (CAT)
acetyl CoA is synthesized from ________
Glucose
Choline is present in plasma at a concentration of about ______ and is taken up into cholinergic neurons by a _______-affinity ___________ transporter.
About _________ molecules of ACh are packaged into each vesicle by a _____________
10 mM
high; Na+/choline
10,000; vesicular ACh transporter.
Both CAT and ACh may be found throughout the neuron, but their highest concentration is in __________.
axon terminals
The presence of __________ is the “marker” that a neuron is cholinergic, only cholinergic neurons contain _____.
CAT
CAT
The rate-limiting step in ACh synthesis is the ____________.
uptake of choline
Uptake of choline is blocked by ______________.
HEMICHOLINIUM
Organic _________ compounds, such as ______________, have a high affinity for sulfhydryl groups, which causes dysfunction of the enzyme choline acetyltransferase. This inhibition may lead to _______ deficiency and can have consequences on _____ function.
mercurial
methylmercury
ACH
motor
During increased neuronal activity the availability of acetyl-CoA from the ____________ is ____regulated as is the uptake of choline into the nerve ending from the ___________.
______ ion appears to be involved in both of these regulatory mechanisms.
mitochondria; up
synaptic cleft
Ca2+
The inactivation of ACh yields _______ and ___________.
choline
acetic acid.
much of the choline used for ACh synthesis comes from the ____________________.
Another source is the breakdown of the _________, —————— .
recycling of choline from metabolized ACh
phospholipid, phosphatidylcholine
• The uptake of ACh into the storage vesicle occurs through an energy- (dependent or independent ?) pump that (acidifies or alkalinizes?) the vesicle.
• The (acidified or alkalinized?) vesicle then uses a _________ transporter (______) to exchange ________ for ACh molecules.
•____________ blocks this carrier molecule.
Dependent; acidifies
acidified; vesicular ACh
VAChT; protons
VESAMICOL
Release of ACh from nerve terminals occurs in (small or large?) quanta – the amount contained in individual vesicles is extruded by ______________.
Response to a nerve AP synchronous release of multiple quanta triggers postjunctional events.
Small; exocytosis
Two toxins interfere with cholinergic transmission by affecting release:
- ___________ toxin inhibits release.
- ____________________ induces massive release and depletion.
Botulinum
Black widow spider venom (BWSV)
Botulinum toxin A & B:
Are highly potent ____toxins produced by _____________ responsible for botulism.
They cause a (short or long?) -lasting loss of cholinergic transmission by interacting with ____________ involved in the ____________ of ACh.
exo; Clostridium botulinum
long; axonal proteins
exocytotic release
Localized injection of a small quantity of botulinum toxin is useful for treating several ________ and other neurological conditions caused by ————- of cholinergic nerves.
spastic
overactivity
In contrast to most other small-molecule neurotransmitters, the postsynaptic action of ACh at many cholinergic synapses (the neuromuscular junction in particular) are not terminated by ________ but by a powerful _______ enzyme, ______________.
reuptake; hydrolytic
acetylcholinesterase (AChE)
AChE
This enzyme is concentrated in the ___________, ensuring a rapid decrease in ACh concentration after its release from the presynaptic terminal.
synaptic cleft
AChE has a very (low or high?) catalytic activity (about _____ molecules of ACh per AChE molecule per second) and hydrolyzes ACh into acetate and choline.
High
5000
The active site of AChE comprises two subsites:
- the ________ site
- the ________ subsite.
Anionic
esteratic
The anionic subsite of AChE accommodates the ____________ amine of acetylcholine as well as other cationic substrates (e.g. ______,_________,_________) and competitive inhibitors.
The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the catalytic triad of three amino acids: ________,__________, and __________
positive quaternary
edrophonium, N-methyl acridinium
serine 203, histidine 447, and glutamate 334.
• Apart from the true cholinesterase(_______), there is the non-specific ___________esterase, also known as ____________esterase. It is found in the __________ and elsewhere in the body to metabolize ingested _________.
AChE
butyrylcholin
pseudocholin
plasma; esters
Differences Between Acetylcholinesterase (A) and Pseudocholinesterase (B)
- A is found distributed in _______,_______, and ________ , while B is in the _______,_______,________, and _____
- A hydrolyses ACh very ______ but methacholine _______. It has ______ action on benzoylcholine and butyrylcholine.
B, on the other hand, hydrolysis ACh _________ , and it’s very ______ on benzoylcholine and butyrylcholine. It has _____ effect on methacholine.
all cholinergic sites, RBC, and grey matter; plasma, liver, intestine, and white matter.
fast; slowly; no
slowly; active; no
Differences Between Acetylcholinesterase (A) and Pseudocholinesterase (B)
(A) is more sensitive to the inhibitory action of ____________ , while (B) is more sensitive to the ____________.
(A) terminates ________ , while B hydrolyzes ____________
physostigmine; organophosphates
ACh action; ingested esters.
There are two broad classes of cholinergic receptors: __________ and ___________.
nicotinic
muscarinic
nicotinic ACh receptors are located at the _______,________, and sparsely in the ———.
NMJ, autonomic ganglia
CNS
The NMJ nicotinic ACh receptor consists of ______ polypeptide subunits:
List them
five
two α subunits and one each of β, δ, and γ.
Nicotinic VS muscarinic ACh receptors
Binds??
Blocked by???
Linked to ??
Nicotine; muscarine
Curare(tubocurarine) ; atropine
Ionic channels; 2nd messenger systems through G proteins
Nicotinic VS muscarinic ACh receptors
Duration and speed of response
Pre or post synaptic?
Mediates ???
Brief and fast; slow and prolonged
Post; pre and post
Excitation; inhibition and excitation
NMJ nicotinic ACh receptor
• A _____-shaped internal ion channel is surrounded by the five subunits.
•The binding surface of the receptor appears to be primarily on the ____ subunits, near the (inner or outer?) surface of the molecule.
• The subunits contain recognition sites for agonists, reversible antagonists, and α-toxins.
funnel; α
Outer
Whereas the NMJ nicotinic receptor is composed of _______ different species of subunit (__________), the neuronal nicotinic receptor also is composed of only ______ subunit types (———- and ______ ).
four; 2 α, β, γ, δ
two
2 α and 3 β
Muscarinic receptors, classified as ______________________ receptors (GPCR) ( __________ Receptors), are located at parasympathetic autonomically innervated visceral organs, on the sweat glands and piloerector muscles, and both post-synaptically and pre-synaptically in the CNS
G protein-coupled
Metabotropic
The muscarinic receptor is composed of a single polypeptide.
• Seven regions of the polypeptide are made up of ________ amino acids arranged in an __________.
• Because each of these regions of the protein is markedly hydro_______, they span the cell membrane ______ times .
20-25 ; α helix
phobic; seven
ACh has (inhibitory or excitatory?) actions at the neuromuscular junction, at the autonomic ganglion, at certain glandular tissues, and in the CNS. It has (inhibitory or excitatory?) actions at certain smooth muscles and at cardiac muscles.
excitatory
inhibitory
G protein is made up of the _______ subunits ___________.
three
α, β and γ.
In response to the altered conformation of the muscarinic receptor, the alpha subunit of the G protein releases bound __________________ and simultaneously binds _______________
guanosine diphosphate (GDP)
guanosine triphosphate (GTP).
