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Cell Membrane Lecture Notes 1 Notes

Pharmacology Notes > BIOL21141 Cell Membrane Structure & Function Notes

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Cell Membrane Structure and Function
Lecture 1 - Overview of Unit
Lecture 2 - Properties of Membranes

Membranes vary between the type of cell and differ for a specific function.
There are many types of membrane surface, with a range of curvatures but the basic components are the same.

Membrane Features
Membranes contain many similar features, and these include:






Sheet-like structures.
Thickness of about 6-10nm.
They have a tendency to form closed boundaries.
Non-covalent assemblies.
Asymmetric.
Fluid, two-dimensional liquid.
Mostly electrically polarised - inside is negatively charged.

Membrane Composition

The Membrane is composed of lipids, proteins and carbohydrates.




The lipids hydrophobic and hydrophilic areas lead to the formation of closed sheets.
The proteins act as pumps, channels, receptors and enzymes.
The lipid to protein ratio is 4:1
Carbohydrates are linked to the lipids and proteins.

Lipids
The definition of a lipid is:

 Any of the large group of fats and fat-like compounds which occur in living organisms and are characteristically soluble in certain organic solvents but only sparingly soluble in water.

The cell membrane contains glycerol-backed phospholipids (glycerophospholipids, or phosphoglycerides) and Sphingosine-backed lipids (sphingophospholipids and glycolipids) and Sterols. Phospholipids

Most phospholipids are based on glycerol with 2x fatty acid (acyl) chains with one head group (phosphate X),
eg: phosphatidyl choline.

The Formation of Lipids

The free energy equation drives the formation of lipid bilayers.



Free energy is the ability to do work.
If the free energy is positive [+] then the reaction is not spontaneous, and work is required.
If the free energy is negative [-] then the reaction is spontaneous.

The Enthalpy is the sum of the kinetic and potential energies.

The Entropy is the disorder of the equation.

Structure of Lipids

Polar solutes, such as acetone, can organise in water without affecting the water structure.

Hydrophobic, non-polar solutes would force the adjacent water molecules to reorganise into a more organised lattice with a decreased entropy and a higher free energy in the hydrophobic effect. 

Lipids are Ampithatic (aka amphilic) and contain both hydrophobic heads and hydrophobic tail regions.

The bilayer ends are exposed to water and so the bilayer then curves round to seal the ends.

Variation of Membranes
There is a huge variety of membrane lipids. These different types of lipid influence:



Membrane dynamics, thickness, fluidity and shape.
Surface biochemistry of membranes with the binding of specific proteins such as enzymes.
The formation of lipid subdomains is important for intracellular trafficking and signalling.
The signalling is the release of lipoid-based metabolites and the binding of signalling molecules.

Phospholipid Variations

Phospholipid head groups and backbones vary through different glycerol backbones and amino alcohol (sphingosine) backbones. 

Glycolipids can only be seen at the cell surface due to its charged properties.

Enzymes

Phospholipases are enzymes which can cleave phospholipids at various points.

Phospholipase D cleaves the phospholipid at its head and leaves Phosphatidate.

Phospholipase C leaves DAG + IP3 which can act as second messengers.

Phospholipase A leaves Lysophoslipid.

Diffusion

Diffusion occurs along membranes, but not across membranes.

The lateral diffusion of lipids is very fast, and phospholipids can diffuse 2µm per second.

The transverse diffusion of lipids (flip flop) is very slow and occurs only once every several hours as it has a very high free energy barrier.

Diffusion equation: S = (4DT)0.5
 S=distance (µm)
 D=diff. coeff. (µm2s-1)
 T=time (s) Structure of Lipids - Acyl Chains

Acyl chains are a range of headgroup structures.
The acyl chain is built from acetyl-coA units and this explains why natural lipids occur always in even numbers.
The shorter the chain the more fluid the lipid, and the average chain length is 18 carbons on average.

Chains can be saturated (no double bonds) allowing free rotation.

Chains can also be unsaturated (double bonds) with a kink at each bond and no free rotation.

The more unsaturated, the more fluid it is.

Sphingolipid acyl chains are both unsaturated and generally longer
(usually 22-24 carbons).

Acyl Chains Melting Temperatures

Organisms that grow at different temperatures can change the lipid composition of the membrane to adapt to changes in temperature
(eg: bacteria & yeasts).

Altering Membrane Fluidity

Membrane fluidity is influenced by temperature and composition.

The membranes mobility generally increases towards the bilayer centre.

The Membrane Temperature (Tm) depends upon:
 The length of the chain.
 The degree of unsaturation.  The headgroup size.

All of these properties influence the lateral packing of PLs/SLs.

Sterols

In animals the sterols are Cholesterol, in yeast it is Ergosterol and in plants it is Stigmasterol.

The effect Sterols have on membranes in eukaryotes is quite complex, but essentially it sits between acyl chains and reduces the fluidity and mobility of the membrane.

Here rigid steroid rings interact with and partially immobilize the outer region of the hydrophobic core causing them to be less fluid.

At high concentrations, which is found in most eukaryotes, the cholesterol prevents the crystallisation of hydrocarbon chains,
thereby inhibiting phase transition, therefore causing the membrane to become more fluid.

 Cholesterol moderate's membrane fluidity.
 Cholesterol also influences membrane thickness as more ordered acyl chains are longer, so the membrane is thicker. Lecture 3 - Membrane Lipids
Lipid Synthesis

Sphingolipid synthesis begins life in the cytosolic leaflet of the Endoplasmic Reticulum and finishes in the luminal leaflet of the Golgi.

Sterols are synthesised in the luminal leaflet of the Endoplasmic Reticulum membranes.

Glycerophospholipids are inserted into the cytosolic leaflet of the ER membrane.
They are synthesised in the cytoplasmic leaflet.

Phospholipid Synthesis 1) Glycerol-backed Phospholipid synthesis begins with a Glycerol backbone.
2) The Glycerol is activated by the addition of a phosphate which makes
Glycerol 3-Phosphate.
3) Next acyl chains, which were made in the cytoplasmic leaflet, are added to the
Glycerol 3-Phosphate from acetyl coenzyme A, generating the intermediate
Phosphatidate.
4) Finally, the head groups are added to the Phosphatidate. The different headgroups are added in different pathways. The phosphate has a high energy bond and so a high energy precursor is required to generate its energy.
5) So, for Phosphatidylserine and Phosphatidylinositol the phosphatidate is charged
(negative) by adding cytodine triphosphate to create the intermediate
CDP - Diacylglycerol. This will then react with Serine or Inositol to generate either for
Phosphatidylserine or Phosphatidylinositol.
5) Whilst for Phosphatidylcholine or Phosphatidylethanolamine there is a different route and the headgroup is charged. The first step is the release of phosphate to form
Diacylglycerol (DAG) and the addition of a charged headgroup (either CDP-Choline or
CDP-ethanolamine) to generate the Phosphatidylcholine or
Phosphatidylethanolamine.

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