PHYSIOLOGY 1PHYSIOLOGY 1

LECTURE 4LECTURE 4

FACILITATED DIFFUSIONFACILITATED DIFFUSION

Facilitated DiffusionFacilitated DiffusionDefinitionDefinition

Facilitated diffusion is the process Facilitated diffusion is the process by which an integral membrane by which an integral membrane protein creates a hole in the protein creates a hole in the biological membrane through biological membrane through which a specific molecule can which a specific molecule can diffuse down it’s concentration diffuse down it’s concentration gradient.gradient.

Facilitated DiffusionFacilitated DiffusionBasic ConceptBasic Concept

Integral membrane proteins are Integral membrane proteins are stimulated to change their stimulated to change their structural conformation such that structural conformation such that an opening in the membrane is an opening in the membrane is created. The transport molecule created. The transport molecule can then diffuse across the can then diffuse across the membrane following it’s membrane following it’s concentration gradient.concentration gradient.

Facilitated DiffusionFacilitated DiffusionDiffusion Through a Biological Diffusion Through a Biological

MembraneMembrane

The oil water partition coefficient (K)The oil water partition coefficient (K) KKxx = [x] = [x]o o / [x]/ [x]ww

Significance - Significance - In general all molecules are In general all molecules are at least to some degree soluble in lipids. at least to some degree soluble in lipids. Therefore, all molecules can, given sufficient Therefore, all molecules can, given sufficient time diffuse across the membrane. The time diffuse across the membrane. The problem is that for most biologically useful problem is that for most biologically useful molecules the cell does not have the time to molecules the cell does not have the time to wait for simple diffusion to supply it’s needs.wait for simple diffusion to supply it’s needs.

Facilitated DiffusionFacilitated DiffusionTransport - Simple Transport - Simple

DiffusionDiffusion

Simple DiffusionSimple Diffusion - - Diffusion through Diffusion through the lipid bilayer is the lipid bilayer is dependent dependent primarily on the primarily on the concentration concentration gradient. Increase gradient. Increase in concentration in concentration gives a linear gives a linear increase in flux.increase in flux.

Facilitated DiffusionFacilitated DiffusionTransport - Carrier Transport - Carrier

MediatedMediated 1. 1. Facilitated DiffusionFacilitated Diffusion 2. 2. Active TransportActive Transport

Carrier mediated Carrier mediated transport requires the transport requires the use of and the cycling use of and the cycling of integral membrane of integral membrane proteins. So the flux proteins. So the flux rate depends on the rate depends on the number of transporters number of transporters and their cycling rate. and their cycling rate.

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

1. Species specific1. Species specific 2. Saturation kinetics - V2. Saturation kinetics - Vmaxmax

3. Competition for transport3. Competition for transport– a. Competitive inhibitiona. Competitive inhibition– b. Noncompetitive inhibitionb. Noncompetitive inhibition

4. Obligative coupling of fluxes4. Obligative coupling of fluxes 5. Higher flux than predicted by 5. Higher flux than predicted by

Fick’s LawFick’s Law

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

Species SpecificSpecies Specific - - Normally a transport protein Normally a transport protein

will only transport a specific will only transport a specific molecule or type of moleculemolecule or type of molecule

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

Saturation KineticsSaturation Kinetics - - In a cell membrane there will In a cell membrane there will

exist at any one time a exist at any one time a specific number of transport specific number of transport proteins for any specific proteins for any specific transport molecule. Since, transport molecule. Since, there also exist a specific there also exist a specific cycling time for a transport cycling time for a transport protein to move a transport protein to move a transport molecule, the system must molecule, the system must become saturated and a become saturated and a maximum flux rate (Vmaximum flux rate (Vmaxmax) ) reached for increasing reached for increasing concentrationsconcentrations

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

Competition for Competition for TransportTransport - -

The presence of an The presence of an inhibitor in the inhibitor in the transport system transport system means that the means that the system will not system will not operate as efficiently.operate as efficiently.– CompetitiveCompetitive– NoncompetitiveNoncompetitive

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

Competition for Competition for TransportTransport - -

Competitive Inhibitor - Competitive Inhibitor - A competitive inhibitor A competitive inhibitor

competes with the transport competes with the transport molecule for the binding site molecule for the binding site on the transport protein - on the transport protein - Increasing concentrations of Increasing concentrations of the transport molecule imply the transport molecule imply that the chance that a that the chance that a transport molecule will bind transport molecule will bind becomes increasingly becomes increasingly greater no effective change greater no effective change in Vin Vmaxmax..

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

Competition for Competition for TransportTransport - -

Noncompetitive Inhibitor - Noncompetitive Inhibitor - A noncompetitive inhibitor A noncompetitive inhibitor

binds to an allosteric site binds to an allosteric site on the transport protein - on the transport protein - This means that a number This means that a number of transport proteins have of transport proteins have effectively been removed effectively been removed from the system, therefore, from the system, therefore, VVmaxmax is decreased. is decreased.

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

Obligative Coupling of Obligative Coupling of FluxesFluxes

If the transport protein If the transport protein is moving two or more is moving two or more transport molecules at transport molecules at the same time the the same time the same ratio of transport same ratio of transport molecules is molecules is maintainedmaintained

Example - Example - Na+K+ATPase moves Na+K+ATPase moves 3 Na+ out and 2 K+ in3 Na+ out and 2 K+ in

Facilitated DiffusionFacilitated DiffusionTransport - Carrier MediatedTransport - Carrier Mediated

Common PropertiesCommon Properties

Higher Flux Rate than Higher Flux Rate than Predicted by Fick’s LawPredicted by Fick’s Law

This is true only for This is true only for physiologically normal physiologically normal concentrations of the concentrations of the transport molecules. transport molecules. At higher At higher concentrations simple concentrations simple diffusion may in fact diffusion may in fact have a higher flux rate.have a higher flux rate.

Facilitated DiffusionFacilitated DiffusionMolecular MechanismsMolecular Mechanisms