Lecture 6 - January 13

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)

Lecture 6 - January 13

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