Membrane transport- L1

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Membrane transport- L1

Faisal I. Mohammed, MD, PhD

Resource: Guyton’s Textbook of Medical Physiology 12th edition.

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Objectives

List trans-membrane transport mechanisms (passive and active)

Describe passive mechanisms (simple diffusion, facilitated diffusion, osmosis, bulk flow)

Describe active mechanisms (primary and secondary active transport mechanisms)

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Major Topics Fluid mosaic model How molecules move across cell membranes

Membrane permeability Molecular gradients Transport mechanisms Ions channels

Equilibrium potential Osmosis and osmotic pressure Tonicity and osmolarity

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A Generalized Cell

1. Plasma membrane

- forms the cell’s outer boundary

- separates the cell’s internal environment from the outside environment

- is a selective barrier

- plays a role in cellular communication

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Structure of the Plasma Membrane

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• barrier to water and water-soluble substances

ions glucose H2Ourea

Lipid Bilayer:

CO2O2N2

halothane

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Plasma Membrane

Flexible yet sturdy barrier The fluid mosaic model - the arrangement of

molecules within the membrane resembles a sea of lipids containing many types of proteins

The lipids act as a barrier to certain substances The proteins act as “gatekeepers” to certain

molecules and ions

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Structure of a Membrane Consists of a lipid bilayer - made up of

phospholipids, cholesterol and glycolipids Integral proteins - extend into or through the

lipid bilayer Transmembrane proteins - most integral

proteins, span the entire lipid bilayer Peripheral proteins - attached to the inner or

outer surface of the membrane, do not extend through it

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Functions of Membrane Proteins

Some integral proteins are ion channels Transporters - selectively move substances

through the membrane Receptors - for cellular recognition; a ligand is

a molecule that binds with a receptor Enzymes - catalyze chemical reactions Others act as cell-identity markers

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Cell Membrane

ionsglucose

H2Ourea

… but, other molecules still get across!

CO2O2N2

halothane

Permeability coefficients (cm/sec)

10-2

10-4

10-8

10-10

10-12

water

ureaglycerol

glucose

Cl-

K+

Na+

10-6

high permeability

low permeability

(** across an artificial lipid bilayer)

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Membrane Permeability

The cell is either permeable or impermeable to certain substances

The lipid bilayer is permeable to oxygen, carbon dioxide, water and steroids, but impermeable to glucose

Transmembrane proteins act as channels and transporters to assist the entrance of certain substances, for example, glucose and ions

Molecular Gradients

Na+

K+

Mg2+

Ca2+

H+

HCO3-

Cl-

SO42-

PO3-

protein

inside(in mM)

141400.510-7

(pH 7.2)10

5-152

75

40

outside(in mM)

14241-21-2(pH 7.4)2811014

5

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• provide “specificity” to a membrane• provide “function”

K+

ion channels carrier proteins

Proteins:

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Diffusion Active Transport

• occurs down a concn. gradient• no mediator or involves a “channel” or “carrier”• no additional energy

• occurs against a concn. gradient• involves a “carrier”

• requires ENERGY

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Passive vs. Active Processes Passive processes – ( downhill) substances

move across cell membranes without the input of any energy; use the kinetic energy of individual molecules or ions

Active processes – (uphill) a cell uses energy, primarily from the breakdown of ATP, to move a substance across the membrane, i.e., against a concentration gradient

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(a) lipid-soluble molecules move readily across the membrane(rate depends on lipid solubility)

(b) water-soluble molecules cross via channels or pores

(a) (b)

Simple Diffusion

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ungated• determined by size, shape, distribution of charge, etc.

Characteristics:

Na+

in

outNa+ and other ions

gated• voltage (e.g. voltage-dependent Na+ channels)• chemically (e.g. nicotinic ACh receptor channels)

Ion Channels

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Ion Channels

Na+

in

out

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Diffusion is the most important means water, gases, waste products, and solute transfer across the endothelium

Exchange of gases, substances, and waste products between the capillaries and the tissue cells

Quantity of substance

moved/time

Diffusion coefficient

CSA

Concentration gradient

Capillary permeability

Capillary surface area

Concentrations (in and out)

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Diffusion Across a Membrane

Fick’s Law of Diffusion:

J= net rate of diffusion in moles or grams per unit timeD= diffusion coefficient of the diffusing solute in the

membrane which is proportional to where S= lipid solubilty, Mwt= molecular weight.

A= area of the membraneC= concentration difference across the membraneX= thickness of the membrane

X

CDAJ

./ MwtS

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Diffusion of lipid-insoluble molecules is restricted to the pores

Movement of solutes across endothelium is complex and involves: Attractions between solute and solvent Interactions between solute molecules Pore configuration Molecular charge > 60,000 MW do not penetrate the endothelium < 60,000 MW penetrate at a rate inversely

proportional to their size

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Lipid-soluble molecules pass directly through the lipid membranes of the endothelium and the pores

Solubility (oil-to-water partition coefficient) provides good index of ease of transfer through endothelium

O2 and CO2 readily pass through endothelium Hb is only 80% saturated entering the

capillaries (diffusion from arterioles) CO2 loading shifts the oxyhemoglobin

dissociation curve in the pre-capillary vessels (countercurrent exchange)

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Simple Diffusion, Channel-mediated Facilitated Diffusion, and Carrier-mediated Facilitated Diffusion

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Channel-mediated Facilitated Diffusion of Potassium ions through a Gated K + Channel

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Glucosetransporter

Glucosegradient

Glucose

Extracellular fluid Plasma membrane Cytosol

1

Glucosetransporter

Glucosegradient

Glucose

Extracellular fluid Plasma membrane Cytosol

1

2

Glucosetransporter

Glucosegradient

Glucose

Glucose

Extracellular fluid Plasma membrane Cytosol

1

2

3

Carrier-mediated Facilitated Diffusion of Glucose across a Plasma Membrane

rate of diffusion

Concen of substance

simple diffusion

Simple vs. Facilitated

facilitated diffusion

What limits maximum rate of facilitated diffusion?

Tmax (Vmax)

rate of diffusion (Co-Ci)

Km

½ Tmax

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Rate of diffusion is limited by − Tmax Transport maximum (Vmax -velocity maximum) of the carrier protein − the density of carrier proteins in the membrane (i.e., number per unit area)The capacity is determined by Tmax and the affinity is determined by Km

Facilitated Diffusion (also called carrier mediated diffusion)

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Factors that affect the net rate of diffusion:

1. Concentration difference (Co-Ci)net diffusion D (Co-Ci)

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Factors Affecting Diffusion Permeability of the cell membrane Temperature Electrochemical gradient of the substance across the

membrane Lipid solubility of the substance Thickness of the cell membrane Size of the molecules M. Wt Size of the ion Charge of the ion

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A B

Net Diffusion

Can a molecule diffuse from side B to side A?

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3. Pressure difference

• Higher pressure results in increased energy available to cause net movement from high to low pressure.

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Special types of passive transport

Bulk flow- pressure difference Filtration- hydrostatic pressure gradient Osmosis-water movement

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Osmosis:- Net diffusion of water -

Osmosis occurs from pure water toward a water/salt solution. Water moves down its concn gradient.

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Osmosis

Net movement of water through a selectively permeable membrane from an area of high concentration of water (lower concentration of solutes) to one of lower concentration of water

Water can pass through plasma membrane in 2 ways:1. through lipid bilayer by simple diffusion2. through aquaporins, integral membrane proteins

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Tonicity and its effect on RBCS

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Osmotic Pressure:

the amount of pressure required to counter osmosis

Osmotic pressure is attributed to the osmolarityof a solution

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Osmotic Pressure Van’t Hoff’s law

= RT nC

= osmotic pressure mmHg

R = ideal gas constant

T = absolute temperature in kelvins (273+centigrade degrees)

C = concentration of solutes in osmoles per liter

n = number of dissociated ions of the substances

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Osmotic Pressure

Oncotic pressure

Reflection coefficient(relative impediment to passage

through capillary wall)

Gas constant Absolute Temperature

Solute (albumin) concentration in and

out

= Ranges between 1 for none permeable molecules to 0 for freely permeable molecules

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Major determinant of osmotic pressure

Solute AMw = 100

Solute BMw = 1000

100 gin 1 L

1000 gin 1L

Which solution has the greatest osmolarity?Which has the greatest molar concentration?Which has the greatest number of molecules?

(6.02 x 1023 particles)

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Relation between osmolarity and molarity

mOsm (millisomolar) = index of the concentration or mOsm/L of particles per liter solution

mM (millimolar) = index of concentration of or mM/L molecules per liter solution

150 mM NaCl =

300 mM glucose =

300 mOsm

300 mOsm

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Estimating Plasma Osmolarity

Plasma is clinically accessible. Dominated by [Na+] and the associated

anions Under normal conditions, ECF osmolarity

can be roughly estimated as:

POSM = 2 [Na+]p 270-290 mOSM

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