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Membranes

Structure of biological membranesFunction of biological membranesExamples of biological membranes

02 The goal of this lecture is to reviewpre-requisite material related to the structure and function of biological membranes and to provide students a further overview of material to be covered in the course.

The sections for this lecture are:

Life is a series of chemical reactions occurring in compartmentalized environments.

The main purpose of life to keep itself alive.

Physiology, the study of how life works, is based on the simultaneous occurrence of the following three concepts:

levels of organizationstructure / function relationshiphomeostatic regulation

Membranes

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Structure

Structure

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Structure

Structure

membranes are phospholipid bilayers interspersed with

• associated proteins having trans-membrane hydrophobic domains (liposoluble domains)

• some of these proteins are ion channels (e.g. Na, K, Cl, Ca)

• some of these proteins are transporters (e.g. GLUT 1-5)

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Structure

Structure

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Structure

(examples of products derived from membrane phospho-lipids)

Structure

some proteins are ion channels

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Structure

some proteins are ion channels

Structure

some proteins are transporters

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Structure

Facilitated diffusion

Structure

Facilitated diffusion

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Structure

Active Transport

Structure

Na/K ATPase pump

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Structure

Secondary active transport

Structure

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Structure

some proteins are - ion channels- transporters

Structure

• membranes are phospho-lipid bilayers interspersed with

• associated proteins having trans-membrane hydrophobic domains (liposoluble domains)

• other proteins are receptors (e.g. G protein-linked receptors)

• other proteins are enzymes and / or receptors (e.g. adenyl-cyclase enzyme / tyrosine-kinase receptors)

plasma

memb.

COOH

2 ECF

ICF

seven - transmembrane

domain receptors

ß - adrenergic and

glucagon receptors among many others

N H

G

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Structure

other proteins are receptors

Structure

EGF insulin

PDGF ANP

GH,

Prl, cytokines

kinase

Cys rich

Cys residues

JAK2

ECF

ICF

COOH

N H2

hydrophobic aa

single - tm

domain receptors

other proteins are enzymes and / or receptors

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Function

Function simple diffusion, diffusion of solutes if membrane is permeable,Fick's first law of diffusionJ= -DA dc/dx J= net rate diffusion, moles or grs per unit time A= area of the planedc/dx= concentration gradient across planeD= diffusion coefficient (proportionality cte)

osmosis, water diffusion through memb. impermeable to ions, van't Hoff's law for osmotic pressure p= iRTmp= osmotic pressurei= # of ions formed by dissociation of a solute R= ideal gas constantT= absolute temperaturem= solute molal conc (moles solute / kg water)

facilitated diffusion, diffusion of solutes through a transporterMichelis-Menten (influx / efflux are symetrical) V= Vmax [S] / Km + [S], V= rate of transport[S]= substrate concentrationVmax= max. rate of transport (influx=efflux)Km= substrate concentration for half Vmax e.g., when Km for influx = Km for efflux, equilibrium is reached at an internal concentration equal to that of the external concentration

active transport, transport against concentration / electrical gradient Michelis-Menten (influx / efflux are asymetrical) V= Vmax [S] / Km + [S], V= rate of transport[S]= substrate concentrationVmax= max. rate of transport (influx efflux)Km= substrate concentration of for half Vmax e.g., when Km for influx= 0.5 mM and Km for efflux= 5 mM, equilibrium is reached at an internal concentration 10x that of the external concentration

electrochemical equilibrium across a semi-permeable membraneNernst equationEa-Eb= -60 mV/z log10 [x]a/[x]b, Ea-Eb= ion electrochemical potential in mVz= valence of the ion (e,g., K=Na=1)[x]a= internal concentration[x]b= external concentrationan electrical potential difference of about 60mV is needed to balance a 10 fold concentration difference of a univalent ion

electrochemical equilibriumacross a semi-permeable membranechord conductance equationEm= gK EK/gT + gNa ENa/gT + gCa ECa/gTEm= membrane potentialgK, gNa, gCa= ion conductances involvedEK, ENa, ECa= ion potential equilibrium involvedgT= total conductance of all ions involvedexpresses transmembrane electrical potential difference as a weighted average of permeable ions' equilibrium potentials involved

Gibbs - Donnan equilibriumsteady-state properties of a mixture of permeant (e.g., initial KCl solution inside B) and impermeant ions (e.g., initial KY solution in side A, where Y is an anion to which the plasma membrane is completely impermeable) across a semi permeable membrane

Under this condition, equilibrium between the A and B sides will be reached when the product of the concentration of the permeant cation K and the permeant anion Cl is equal in side A and side B.

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Function

Fick's first law of diffusionJ= -DA dc/dx J= net rate diffusion, moles or grs per unit time A= area of the planedc/dx= concentration gradient across planeD= diffusion coefficient (proportionality cte)

Diffusion

Function

osmosis, water diffusion through a membrane impermeable to ions, van't Hoff's law for osmotic pressure p= iRTmp= osmotic pressurei= # of ions formed by dissociation of a solute R= ideal gas constantT= absolute temperaturem= solute molal conc (moles solute / kg water)

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Function

osmosis, water diffusion through a membrane impermeable to ions, van't Hoff's law for osmotic pressure p= iRTmp= osmotic pressurei= # of ions formed by dissociation of a solute R= ideal gas constantT= absolute temperaturem= solute molal conc (moles solute / kg water)

osmosis

Function

facilitated diffusion, diffusion of solutes through a transporterMichelis - Menten (influx / efflux are symetrical) V= Vmax [S] / Km + [S], V= rate of transport[S]= substrate conc.Vmax= max. rate of transport (influx=efflux)Km= substrate conc. for half Vmax e.g., when Km for influx = Km for efflux, equilibrium is reached at an internal concentration equal to that of the external concentration

(e.g. Ca)

(e.g. Glucose)

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Function

facilitated diffusion of solutes through a transporterMichelis-Menten (influx / efflux are symetrical) V= Vmax [S] / Km + [S], V= rate of transport[S]= substrate conc.Vmax= max. rate of transport (influx=efflux)Km= substrate conc. for half Vmax e.g., when Km for influx = Km for efflux, equilibrium reached at internal conc = to that of external conc.

Function

active transport, transport against concentration / electrical gradient Michelis-Menten (influx / efflux are asymetrical) V= Vmax [S] / Km + [S], V= rate of transport[S]= substrate concentrationVmax= max. rate of transport (influx efflux)Km= substrate concentration of for half Vmax e.g., when Km for influx= 0.5 mM and Km for efflux= 5 mM, equilibriumis reached at an internal concentration 10x that of the external concentration

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Function

electrochemical equilibrium across a semi-permeable memb.Nernst equationEa-Eb= -60 mV/z log10 [x]a/[x]b, Ea-Eb= ion electrochemical potential in mVz= valence of the ion (e,g., K=Na=1)[x]a= internal concentration[x]b= external concentrationan electrical potential difference of about 60mV is needed to balance a 10 fold concentration difference of a univalent ion

electrochemical equilibrium across a semi-permeable memb.chord conductance equationEm= gK EK/gT + gNa ENa/gT + gCa ECa/gTEm= membrane potentialgK, gNa, gCa= ion conductances involvedEK, ENa, ECa= ion potential equilibrium involvedgT= total conductance of all ions involvedexpresses transmemb electrical potential difference as weighted average of permeable ions' equilibrium potentials involved

Gibbs - Donnan equilibriumsteady-state properties of a mixture of permeant (e.g., initial KCl solution inside B) and impermeant ions (e.g., initial KY solution in side A, where Y is an anion to which the plasma membrane is completely impermeable) across a semi permeable membrane

Under this condition, equilibrium between the A and B sides will be reached when the product of the concentration of the permeant cation K and the permeant anion Cl is equal in side A and side B.

(important concepts for later lectures)

Function

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Examples

potential energy at themembrane level isassociated with pumps

e.g. electrical gradient

e.g. conc. gradients

e.g. action potential

Examples

intracellular calciumis an important 2ndmessenger

e.g. release

e.g. contraction

e.g. communication

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Examples

electrochemical andconcentration gradientsfor sodium

e.g. Na homeostasis

e.g. absorption in gut

e.g. renal absorption

Examples

transmembrane Naas source of potentialenergy for work

e.g. absorption of sugars

e.g. absorption of amino acids

e.g. Na / Ca and Na / H exchange

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Examples

water goes where sodium goes

e.g. absorption of water

e.g. countercurrent mech.

e.g. diuretics and alcohol

Examples

glands secrete specificsubstances to the extra-cellular fluid (ECF)

e.g. exocrine secretion

e.g. endocrine secretion