receptors bind specific ligands

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Receptors Bind Specific Ligands mon ligands for receptors include ….. hormones – alter target cell metabolic behavior neurotransmitters – lead to action potential of ne Signal Transduction

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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 Presentation

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Page 1: 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

Page 2: Receptors Bind Specific Ligands

Neuron schematic

axon

myelin sheath

dendrites

nerve endings nt release

nt receptors Cell body

synapse

Page 3: Receptors Bind Specific Ligands

Membranes are electrically polarized

Page 4: Receptors Bind Specific Ligands

Ion Channels in Nerve Signaling

Page 5: Receptors Bind Specific Ligands

Molecular Components of Nerve Transmission

Acetylcholine: neurotransmitterAcetylcholine Receptor

choline acetyltransferse : enzyme

Na+/K+ ATPase (Pump) : TransporterAcetylcholine Esterase : enzyme

Na+ voltage-gated channelK+ channel – (efflux)

Page 6: Receptors Bind Specific Ligands

Signal Transmission in Nerve Cells

Synapse (50nm): ACh diffusion

Along Cell : depolarisation very rapid

Page 7: Receptors Bind Specific Ligands

Synapse Area

ACh

Na+

ACh

Na+

Na+A + Ch

Page 8: Receptors Bind Specific Ligands

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

Page 9: Receptors Bind Specific Ligands

The Acetylcholine Receptor• Nicotinic acetylcholine receptor:

– Ion channel for influx of Na+, Ca2+

– Gate opened by acetylcholine

Page 10: Receptors Bind Specific Ligands

AChR

Page 11: Receptors Bind Specific Ligands

AChRa2bgd

268,000 MW

Page 12: Receptors Bind Specific Ligands

O + ||

(CH3)3 – N - CH2 - CH2 – O – C – CH3

acetylcholine

Page 13: Receptors Bind Specific Ligands

closed form

open formLL LLL

S

S

SS

S

ACh

ACh

L

LL

LL

SSS

SS

ACh

ACh

Page 14: Receptors Bind Specific Ligands

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

Page 15: Receptors Bind Specific Ligands

Acetylcholine

Acetylcholine esterase

O ||CH3-C-O-CH2-CH2-N-(CH3)3

+

O ||CH3-C-O- + HO-CH2-CH2-N-(CH3)3

+

Page 16: Receptors Bind Specific Ligands

ACh binding to AChR

• Blocked by snake venom proteins• Curare has same effect• Antibodies in Myasthenia Gravis• Result is Paralysis• Tetrodotoxin blocks Na+ channel

Page 17: Receptors Bind Specific Ligands

Bungarotoxin (a snake venom)

Binding to segment of AChR (red)

Page 18: Receptors Bind Specific Ligands

Acetylcholine Esterase InhibitorsParathion: insecticideSarin: Nerve Gas

As Alzheimer’s MedicationHuperazine A: plant alkaloid & Chinese folk medicine

Aricept (Donepezil)