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BIOCHEMISTRY

7-MEMBRANES & TRANSPORT


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MEMBRANES & TRANSPORT

INTRODUCTION
Membranes & Transport
Introduction
◗ Membranes = gateways into and out of the cell.
◗ Membrane composition = lipids & proteins.
◗ Membrane functions.
• Barrier properties.
• Excitability
• Transport.
• Compartmentalization.
• Signal transduciton.

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MEMBRANES & TRANSPORT

MEMBRANE ORGANIZATION
Lipids & Proteins
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Membranes & Transport
Membrane Organization
◗ Lipid composition of biomembranes.
• Phosopholipids = most common lipid.
• Long fatty acid tail = hydrophobic (aliphatic).
• Polar head groups = hydrophobic.
• C1 position (glycerol) – attaches to saturable fatty
acids.
• C2 position – attaches to unsaturated fatty acids.
• C3 position – is phosphorylated and attaches to
small polar head groups.
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Membranes & Transport
Membrane Organization
◗ Phospholipids form basic structure of membranes.
• Amphipathic molecules = both:
• Hydrophobic = fatty acid tails.
• Hydrophilic = small polar head groups.
• When phospholipids are hydrated:
• Form micells = liposomes.
• Bipolar structures.
• Backbone of membranes.
• Other important lipids in membranes.
• Demonstrate a surface specificity.

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MEMBRANES & TRANSPORT

CURRENT MEMBRANE
STRUCTURAL MODEL
Membranes & Transport
Membrane Structural Model
◗ Mosaic model = globular proteins embedded in
fluid-like phospholipid layer.
• Singer and Nicolson model – 1970s.
• Polar heads = external surfaces and non-polar tails are
internal.
• Rarely flip-flop.
• Proteins – capable of lateral diffusion.
• Integral (transmembrane) proteins – alpha helix (non-polar
amino acids).
– Ion transfer function as an example.
• Peripheral proteins – extrinsic.

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MEMBRANES & TRANSPORT


TYPES OF TRANSPORT
PROCESSES
Simple Diffusion
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Membranes & Transport
Types of Transport Processes
◗ Simple diffusion (passive transport).
• Hydrophobicity is important = easy passage
through the cell membrane of small, nonpollar
and uncharged polar molecules (O2 and
ethanol).
• Simple concentration gradient dynamics.
• Usually no carrier proteins are involved.

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MEMBRANES & TRANSPORT


TYPES OF TRANSPORT
PROCESSES
Transport Mediated by Membrane
Proteins
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Membranes & Transport
Types of Transport Processes
◗ Transport mediated by membrane proteins.
• Work by one of two mechanisms.
• Facilitated diffusion.
• Active transport.

Facilitated diffusion.
• Channel (membrane proteins) = acquaporins.
• Involved principally in water movement.
• No energy required.
• Small, uncharged molecules.

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Membranes & Transport
Types of Transport Processes
◗ Transport kinetics: facilitated vs simple
diffusion.
• Simple diffusion rate directly proportional to
substrate concentration.
• Facilitated diffusion is a saturable process:
• Transporter protein channel becomes saturated with
substrate.
• Rate > than simple diffusion.

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Membranes & Transport
Types of Transport Processes
◗ Active transport.
• Substances moved against their concentration gradient
= need for energy.
• Involves transport of larger molecules, examples:
• Polar and/or charged molecules.
• Amino acids and proteins.
• Sugars.
• Need for protein assistance as transporters which can
be very specific for the molecule to be transported
similar to the enzyme-substrate phenomena.

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MEMBRANES & TRANSPORT


TYPES OF TRANSPORT
PROCESSES
Active Transport Processes
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Membranes & Transport
Active Transport Process
◗ ATP = energy currency of the cell.
• ATP – hydrolized = ADP + Pi (free energy).
◗ Primary vs secondary active transport systems.
• Primary = ATP use directly.
• Secondary = uses electrochemical gradient (a form of
stored energy) of Na+ and H+ and/or membrane
potential produced by primary active transport
processes to move molecules.
• Sugars.
• Amino acids.

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Membranes & Transport
Active Transport Process
◗ What is the electrochemical gradient?
• A combination of the voltage gradient
(membrane potential) and the concentration
gradient of the ion across the membrane.
• These 2 forces may act in same or opposite
directions but possess a potential in that they
possess stored energy to drive such processes.

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Membranes & Transport
Active Transport Process
◗ Proteins participating in these secondary active
transport systems are called:
• Uniporters.
• Synporters.
• Antiporters.
◗ The principle is that the movement of one
substrate against its concentration gradient can be
driven by movement of another substrate (usually
cations such as Na+ or H+) down its gradient.
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Membranes & Transport
Active Transport Process
◗ Primary active transport system = ion pumps are
the most important class.
• Called:
• Ion transporting ATPases.
• Pump ATPases.
• Example – Na+/K+-ATPase helps to maintain cellular
ion gradients = a transmembrane protein.
• Creates an electrochemical gradient of Na+ that produces the
driving force for nutrient uptake and the discharge of the
electrochemical gradient in nerve transmission.

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Membranes & Transport
Active Transport Process
• Example – Na+/K+-ATPase helps to maintain cellular
ion gradients.
• Na+ = 10x greater concentration on outside of cell than on its
inside due to this ion pump activity.
• Na+/K+ ATPase is electrogenic, pumping out 3 Na+ ions and
pumping in 2 K+ ions = inside negative membrane potential.
– K+ leaks back out along its concentration gradient through
channel > negativity on inside of cell membrane.
• This drives a symport mechanism by powering uptake of
molecules against their concentration gradient.

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MEMBRANES & TRANSPORT


TYPES OF TRANSPORT
PROCESSES
Transport by Channels & Pores
Membranes & Transport
Transport by Channels & Pores
◗ Channels and pores = tunnels across the
membrane involving ion movement.
• Conformational changes by voltage or ligand (binding)
phenomena can open or close channels.
• Characteristics:
• Function in ion movements.
• Movement is faster than through transporters.
• Types:
• Voltage gating.
• Ligand gating.
• Signal gating.

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Membranes & Transport
Transport by Channels & Pores
◗ Pores.
• Non-selective.
• Restricts movement according to size.
• Handles small molecules such as water.
• Important pore types – examples.
• Gap junctions = cluster of small pores.
– Formed between two cell membranes.
– Molecules are < 1 kDa in size to pass through.
– Allows for cell-cell communication.
• Nuclear pores.

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MEMBRANES & TRANSPORT


EXAMPLES OF TRANSPORT
SYSTEMS AND THEIR
COUPLING
Transport Systems & Their
Coupling
◗ Glucose transporters (uniporters).

◗ Ca2+ transport and mobilization in muscle.

◗ Role of Na+/K+ -ATPase in glucose uptake.

◗ Proton pump in the stomach.


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What Happens When a Ion Channel
Malfunctions?
Clinical Considerations.
◗ Cystic fibrosis - a lung dysfunction.
• Most common potentially lethal autosomal dominant
disease of white populations (1/2500 infants).
• A Cl- ion channel mutation.
• < channel activity = > Cl- concentration.
– Exocrine pancreas insufficiency.
– > Cl- in sweat.
– Male infertility.
– Airway disease.
– Channel called cystic fibrosis transmembrane conductance
regulator (CFTR) = ABC transporter or gated Cl- channel.

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What Happens When a Ion Channel
Malfunctions?
Clinical Considerations.

◗ Cystic fibrosis - a lung dysfunction.


• Airway disease.
• Lung dysfunction = > mortality.
• < channel activity = < lung transepithelial
electrolyte transport and fluid transport = > sticky
mucous in lungs = > infections due to > capture of
bacteria = > lung degeneration = mortality.

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Membranes & Transport
Learning Objectives
◗ Describe the current plasma membrane
structural model.
◗ Understand Membrane organization in
relation to its lipid and protein components..
◗ What are the structural & metabolic roles of
membranes?

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Membranes & Transport
Learning Objectives
◗ Identify the types of membrane transport
processes.
◗ Explain the importance and examples of
transport systems and their coupling.
◗ How are the following diseases related to
cellular transport systems?
• Cystic fibrosis.
• Heart disease.
• Gastric disorders.
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