7-membranes & Transport

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BIOCHEMISTRY 7-MEMBRANES & TRANSPORT Return to Menu

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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. 3

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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. 8

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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. 11

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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. 15

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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. 24

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. 25

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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. 27

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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).

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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. 31

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.

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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. 33

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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. 35

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. 39

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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).

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Ca2+ transport and mobilization in muscle.

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

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Proton pump in the stomach. 46

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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. 50

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. 53