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8/7/2019 Lecture 6 - January 13
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Biology 2A03
Lecture 6
Signal transduction
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2
Osmosis
Water diffusion: although water is polar it has high permeabilityin membranes due to its small size
Flux can be increased by the presence of aquaporins = proteinchannels.H2O concentration depends on the # of dissolved particles
Total [solute] in solution determines osmolarity (colligativeproperties)1 mole of dissolved particles = 1 osmolar solution
e.g. 1M of glucose in solution = 1 osmolebut 1M of NaCl = 2 osmoles since it ionizes in solution to
Na+ and Cl-The higher the osmolarity of a solution the lower the H2Oconcentration
Osmosis in the direction of higher osmolarity (or lower[H2O])
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Compare to osmolarity
Relates the osmolarity of a solution relative to normal extracellularfluid without regard to penetrating or nonpenetrating nature ofsolutes
A solution can be isoosmotic at 300 mOsm but hypotonic due topenetrating solutes
isoosmotic But hypotonic
300 mOsm >300 mOsmnonpenetrating
penetrating
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4 features of signal transduction pathways:
Signal Transduction Pathways detect intercellular messengers andconvert them into a biologically meaningful response
2) Amplification: 1 receptorbindingcan leadto 1,000,000 products
3) Desensitization / adaptation:
4) Integration:
response- +
1) Specificity:
Can also have messenger bind to multiplereceptors with different affinities
Thesignal molecule fitsinitsreceptor
whileothersdonot
Seetable 5.1
Feedbackshutsoff
receptororremovesit
Outcometheresultofintegrationof
both receptorinputs
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ReceptorsThe magnitude of a cells response depends on:
1) the messengers concentration
2) the # of receptors present
3) affinity of receptor for messenger
Show characteristics very similarto enzymes
Fig 5-9Fig 5-10
Can become saturated withmessenger
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An increase in the # of receptors
increases the % bound with messenger
Change in affinity for messenger
Can increase # of bound receptorsat the same [messenger]
Fig 5-10
Or50% of the receptors areBound at a lower [messenger]
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Receptors can be intracellular:
RM
R
SeeFig
5-11
bind to lipophilic messengers
alters synthesis of a specific protein
-act as transcription factors
Receptors can be located in the cytosol of in the nucleus
e.g. steriods = hormones
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Receptors can be membrane bound:1) Channel-linked: (e.g binding opens ion channel)
3 main types
Fig 5-12
This is an example of
fast channelChannel also acts as theReceptor
Allows channel to open
quickly and briefly
Called ligand gatedchannels
Bind lipophobic messengers
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2) Enzyme-linked:
Binding activates tryosine kinase activitywhich phosphorylates a protein a tryrosin
Ligand-binding domain on extracellular surface .And an enxyme active site on intracellular side
Fig 5-13
e.g. insulinreceptor
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3) G-protein-linked: (activate membrane proteins called G-proteinsand begins a signalling cascade)
G-proteins can be stimulatory (Gs) orinhibitory (Gi)
2. Often activates an enzyme
Fig 5-14
1. Regulates a protein channel
-subunit binds GTP
to becomeactive
e.g. Can open or close aslow ion channel- Channel does not act asreceptor
e.g. adenylate cyclase toproduce cAMP
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Important 2nd messengers are:1) Ca2+
2) cAMP
3) cGMP4) DAG5) Eicosanoids6) IP3
Second messengers
Act as chemical relays from the plasma membrane to thebiochemical machinary inside the cell
Table 5-3Fig 5-16Fig 5-17Fig 5-18
Intercellular chemical messenger which reaches the cell surface
is called the first messengerThe intracellular messenger produced by the binding of the firstmessenger is called the second messenger
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F
Extracellular fluidMessenger
1Receptor
KE
GDP GTP
GDP GTP
2
E
Amplifier
enzymeSecond
messenger
Protein kinase
Activates
enzyme
Protein
ATP
+Protein P
ADP
+
3
4
5
6
Response in cellCytosol
Substrate
Blood borne hormone
epinephrine
1x molecules
Beta adrenergicreceptor
Adenylate
cyclase
G-proteinstimulatory ATP
PKAinactive PKAactive
10x molecules
UsingATP,
formscAMP
20x molecules
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glycogen Glucose 1-P
inactivePhosphorylase b
Kinase
activePhosphorylase b
Kinase
inactiveGlycogen
phosphoryase b
activeGlycogen
phosphoryase a
(100x molecules)
(1000x molecules)
(10,000x molecules)
Amplificationof hormone signal
Adrenergic receptor can be desensitized by phosphorylation
Response of the cell (e.g. glycogen breakdown in liver cells)PKA
active
10x molecules
PKAactive
Glycogen synthase (inactive)
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