Receptors Bind Specific Ligands
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Transcript of Receptors Bind Specific Ligands
Receptors Bind Specific Ligands
Common ligands for receptors include ….. hormones – alter target cell metabolic behavior neurotransmitters – lead to action potential of neuron
Signal Transduction
Neuron schematic
axon
myelin sheath
dendrites
nerve endings nt release
nt receptors Cell body
synapse
Membranes are electrically polarized
Ion Channels in Nerve Signaling
Molecular Components of Nerve Transmission
Acetylcholine: neurotransmitterAcetylcholine Receptor
choline acetyltransferse : enzyme
Na+/K+ ATPase (Pump) : TransporterAcetylcholine Esterase : enzyme
Na+ voltage-gated channelK+ channel – (efflux)
Signal Transmission in Nerve Cells
Synapse (50nm): ACh diffusion
Along Cell : depolarisation very rapid
Synapse Area
ACh
Na+
ACh
Na+
Na+A + Ch
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
The Acetylcholine Receptor• Nicotinic acetylcholine receptor:
– Ion channel for influx of Na+, Ca2+
– Gate opened by acetylcholine
AChR
AChRa2bgd
268,000 MW
O + ||
(CH3)3 – N - CH2 - CH2 – O – C – CH3
acetylcholine
closed form
open formLL LLL
S
S
SS
S
ACh
ACh
L
LL
LL
SSS
SS
ACh
ACh
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
Acetylcholine
Acetylcholine esterase
O ||CH3-C-O-CH2-CH2-N-(CH3)3
+
O ||CH3-C-O- + HO-CH2-CH2-N-(CH3)3
+
ACh binding to AChR
• Blocked by snake venom proteins• Curare has same effect• Antibodies in Myasthenia Gravis• Result is Paralysis• Tetrodotoxin blocks Na+ channel
Bungarotoxin (a snake venom)
Binding to segment of AChR (red)
Acetylcholine Esterase InhibitorsParathion: insecticideSarin: Nerve Gas
As Alzheimer’s MedicationHuperazine A: plant alkaloid & Chinese folk medicine
Aricept (Donepezil)