receptors bind specific ligands
DESCRIPTION
Receptors Bind Specific Ligands. Signal Transduction. Common ligands for receptors include ….. hormones – alter target cell metabolic behavior neurotransmitters – lead to action potential of neuron. synapse. nt receptors. dendrites. axon. myelin sheath. Cell body. nerve endings - PowerPoint PPT PresentationTRANSCRIPT
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Receptors Bind Specific Ligands
Common ligands for receptors include ….. hormones – alter target cell metabolic behavior neurotransmitters – lead to action potential of neuron
Signal Transduction
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Neuron schematic
axon
myelin sheath
dendrites
nerve endings nt release
nt receptors Cell body
synapse
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Membranes are electrically polarized
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Ion Channels in Nerve Signaling
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Molecular Components of Nerve Transmission
Acetylcholine: neurotransmitterAcetylcholine Receptor
choline acetyltransferse : enzyme
Na+/K+ ATPase (Pump) : TransporterAcetylcholine Esterase : enzyme
Na+ voltage-gated channelK+ channel – (efflux)
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Signal Transmission in Nerve Cells
Synapse (50nm): ACh diffusion
Along Cell : depolarisation very rapid
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Synapse Area
ACh
Na+
ACh
Na+
Na+A + Ch
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Nerve Transmission Chronology Nerve cell depolarised (stimulus)
Releases ACh into next synapse 10nM 300 mM in 1ms
ACh binds AChR a2bgd
Na+ channel opens - depolarisation.opens voltage gated Na+ channels & action potential
Na+/K+ pump removes Na+
ACh-esterase destroys ACh
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The Acetylcholine Receptor• Nicotinic acetylcholine receptor:
– Ion channel for influx of Na+, Ca2+
– Gate opened by acetylcholine
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AChR
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AChRa2bgd
268,000 MW
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O + ||
(CH3)3 – N - CH2 - CH2 – O – C – CH3
acetylcholine
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closed form
open formLL LLL
S
S
SS
S
ACh
ACh
L
LL
LL
SSS
SS
ACh
ACh
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ACh binding to AChR Ka = 108 M-1s-1
binding time = 100 ms closed open = 30 ms stays open ~ 1ms impulse rate ~ 1000 s-1
Acetylcholine Esterase kcat = 25,000 s-1
KM = 12.5 mM kcat/KM = 2 x 108 M-1s-1
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Acetylcholine
Acetylcholine esterase
O ||CH3-C-O-CH2-CH2-N-(CH3)3
+
O ||CH3-C-O- + HO-CH2-CH2-N-(CH3)3
+
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ACh binding to AChR
• Blocked by snake venom proteins• Curare has same effect• Antibodies in Myasthenia Gravis• Result is Paralysis• Tetrodotoxin blocks Na+ channel
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Bungarotoxin (a snake venom)
Binding to segment of AChR (red)
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Acetylcholine Esterase InhibitorsParathion: insecticideSarin: Nerve Gas
As Alzheimer’s MedicationHuperazine A: plant alkaloid & Chinese folk medicine
Aricept (Donepezil)