Lipids and Membranes

What are lipids?

• Non-polar organic compounds

• Not soluble in water

• Highly soluble in non-polar organic solvents e.g. chloroform

3 main biological functions of lipids

• Membrane formation

• Energy storage

• Precursors to signalling molecules

What is the principal component of most lipids?

Fatty acids

Structure of fatty acids

• Carboxylic acid

  » polar, hydrophilic

• Unbranched hydrocarbon chain

  » non polar, hydrophobic

  » can be saturated or unsaturated

  » between 14 to 22 Cs long

What determines the physical properties of a fatty acid and therefore its biological function?

• The length of the hydrocarbon chain

• The degree of unsaturation

How are chemical structure, physical property and biological function of a molecule linked?

Chemical structure —> Physical properties —> Biological function

Draw the structures of stearic acid, oleic acid and linoleic acid

What is the similarities and differences between these fatty acids?

• All C18 lipids (contain 18 C atoms)

• Contain different numbers of C=C bonds

Why is the number of C=C bonds a fatty acid has important?

• Affects the melting point

• As the number of C=C bonds increases, the melting point of the lipid decreases

Melting point of fatty acids

Saturated fatty acid over 8 Cs long = melting point over 25, solid at room temp

Saturated fatty acids 8 Cs or less and unsaturated fatty acids = melting point below 25, liquid at room temp

State whether stearic acid, oleic acid and linoleic acid are solid or oil at room temp

Stearic acid (saturated) = solid

Oleic acid (unsaturated) = oil

Linoleic acid (unsaturated) = oil

Why do unsaturated fatty acids have a lower melting point?

• When an alkene is present in a fatty acid, geometric isomerism occurs (can be cis or trans isomer)

• Most unsaturated fatty acids are found in the cis conformation

• The presence of cis alkenes means that the hydrocarbon chains are not straight chains occupying minimal space

• Instead, they are bulky and the cis alkenes cause the hydrocarbon chain to bend

• More double bonds = more bending

• Bent = hydrocarbon chains unable to pack together as tightly = fewer hydrophobic interactions = lower MP

Why do saturated fatty acids have a higher melting point?

• Hydrocarbon chain adopts a linear conformation

• This means it can pack more closely together with neighbouring molecules

• This allows more hydrophobic interactions to form = higher MP

Why is it important that the fatty acids in membranes are unsaturated?

• Fatty acids cannot pack together as closely

• This leads to a membrane which can move more freely

• Increasing membrane fluidity

What are polyunsaturated fatty acids?

Fatty acids with more than one C=C double bond

Why are polyunsaturated fatty acids important in the diet?

Precursors for biosynthesis of important signal molecules e.g. arachidonic acid is a precursor for prostaglandins

• These signalling molecules are hormones which control blood flow and smooth muscle contraction

Why are polyunsaturated fatty acids known as essential fatty acids?

We cannot synthesise them in the body - we need to obtain them from the diet

2 types of polyunsaturated fatty acids

1. Omega-3 (first double bond occurs 3 carbons from the end of the chain)

2. Omega-6 (first double bond occurs 6 carbons from the end of the chain)

What type of polyunsaturated fatty acid is arachidonic acid

Omega-6

Types of lipids

1. Triacylglycerols AKA Triglycerides

2. Phospholipids

3. Cholesterol

Triacylglycerols (Triglycerides)

Main function

• Energy storage

• Fatty acids are storied as triacylglycerols in fat cells, and then are released by hydrolysis when needed for energy production

Triacylglycerols (Triglycerides)

How are they formed?

• 3 fatty acids + 1 glycerol

• In a condensation reaction

• Forms 3 ester bonds

• Loses 3 molecules of water

Triacylglycerols (Triglycerides)

2 types

1. Fats

• Triacylglycerols which are solid at room temp (saturated with more than 8 Cs)

• Common in animals e.g. butter

2. Oils

• Triacylglycerols which contain more unsaturated fatty acids = liquid at room temp

• Common in plants e.g. olive oil

Phospholipids

Why are phospholipids the most important structural lipids?

They are the main component of biological membranes

Phospholipids

What does it mean by phospholipids are amphipathic?

Contain both hydrophobic and hydrophilic regions in the same molecule

• Polar hydrophilic head group

• Non-polar hydrophobic lipid tails

Phospholipids

Structure

• 2 fatty acids + glycerol + phosphate group

• In a condensation reaction

• The phosphate group is linked to a small polar group e.g. choline, serine, ethanolamine

• The hydrophobic tail is formed from 2 fatty acids which are linked via ester bonds to the glycerol

Phospholipids

What does the head group determine?

• The head group determines the overall charge of the phospholipid

• Phospholipids can be positive, negative or neutral

• This influences the overall charge of cell membranes

Cholesterol

Structure

Multicyclic hydrocarbon with 4 rings and a short alphatic chain

Cholesterol

How is cholesterol obtained?

• From the diet

• Synthesised in the liver

Cholesterol

Role of cholesterol

• Increases membrane fluidity » this allows the membrane to move to fix itself

• Biosynthetic precursor to many important biology molecules:

  E.g. Vitamin D, which is important for calcium absorption from the diet

  E.g. Bile acids like cholic acid, which emulsify fats in digestion

  E.g. Steroid hormones, like testosterone and progesterone

Other types of complex lipids

• Waxes

• Sphingolipids

• Glycolipids

Waxes

Structure?

Where are they found?

• Complex mix of different lipids

• Each lipid has a simple structure with a single ester

• Contains saturated fatty acids

• Found in the waterproof coating of organisms

Sphingolipids

Where are they found?

What is their function?

• Found in all eukaryotes, associated with membranes

• They protect the external cell surface by increasing mechanical stability of the membrane

• This helps membranes to repair themselves

Glycolipids

Structure

Where are they found?

What is their function?

• Lipid molecules associated with sugar molecules, like cerebroside

• Found on cell surfaces

• Involved in cell recognition and signalling

What concept is linked to membranes?

Compartmentalisation

• Lipid membranes create compartments which are essentially for cell survival

• This allows organelles to be kept separate from the rest of the cell

• Membranes are not just passive barriers, they are an active part of the cellular machinery

Role of membranes

• Provides structure

• Controls the amount of nutrients, preventing compounds the cell requires from leaking out

• Controls the internal conditions of each compartment » so controls which reactions can occur

• Controls which molecules come in and out of each compartment » brings in nutrients and removes waste

• Allow cellular communication » allow cells to send and receive signals from other cells via cell surface receptors

Why is it important that organelles have their own membranes?

• Keeps them separate from the rest of the cell. This is called compartmentalisation

• This means different processes can happen within the cell at the same time

• E.g. Metabolism

  • Catabolism and anabolism need to be kept separate for the cell to function properly

  • Lysosomes contain digestive enzymes to break down waste macromolecules

  • These enzymes need to be separated from the cytoplasm so the cell can synthesis new macromolecules without them being immediately digested

  • Compartmentalisation of digestive enzymes in lysosomes therefore allows the cell to simultaneously break down macromolecules and synthesise new ones

Give an example of how membranes can allow cellular processes to occur

• Mitochondria have a double membrane

• ATP synthesis is carried out by proteins on the inner mitochondrial membrane

• The membrane provides the ideal compartment and a large surface area for this reaction to occur

What is the main component of lipid membranes?

Phospholipids

How do phospholipids form a structure such as the lipid membrane?

• The amphipathic nature of phospholipids cause them to self-assemble when they are in aqueous environments

• So that the hydrophilic heads are on the outside and the hydrophobic tails are on the inside

• This structure is held together by hydrophobic interactions between the fatty acid tails and the attraction between the polar head groups and water » there are no covalent interactions, only non-covalent

What are the different types of self-assembled structures that phospholipids can form?

1. Micelles

• Single layer of lipids with hydrophobic tails inside and hydrophilic heads outside which associate with water

• Formed by phospholipids with a one fatty acid tail

2. Phospholipid bilayers

• Hydrophobic tails inside and hydrophilic heads outside which associate with water

• Formed by phospholipid with two fatty acid tails

3. Liposomes

• Spherical structures

• Formed from a lipid bilayer which has self-sealed

• Have a hollow aqueous cavity in their centre which can be used for drug delivery

  E.g. use of liposomes for delivery of mRNA for Covid-19 vaccines

Characteristics of phospholipid bilayer

1. Fluid

• Lipids in the bilayer are able to move freely

• This makes the bilayer flexible and means they are able to reseal if damaged

2. Impermeable to water and polar compounds e.g. sugars and amino acids

• This is because the centre of the bilayer is extremely hydrophobic and does not allow polar molecules to cross

• This prevents the leakage of essential nutrients

3. Permeable to small, uncharged, lipid soluble compounds e.g. oxygen, carbon dioxide, nitrogen, glycerol, urea, steroids

4. Permeable to water via special transmembrane protein channels called aquaporins

• This allows the cell to regulate osmotic pressure

Why is the plasma membrane being impermeable to polar compounds a problem?

• Means that essential nutrients and ions required by the cell cannot pass through the bilayer

• So the cell membrane requires transport proteins for these molecules

Define fluidity

How much the components of a membrane can move

What does the fluidity of a membrane depend on?

The structure of the lipids it contains

• Saturated fatty acids pack more tightly together = form dense bilayers = more rigid = less fluid

• Shorter fatty acids OR unsaturated fatty acids cannot pack as closely together = form a looser bilayer = more fluid

The amount of cholesterol in the membrane

• Cholesterol disturbs the bilayer by disrupting the packing of fatty acids = increases fluidity

Why are membranes in animals and plants fluid?

• They are rich in unsaturated fatty acids

• They contain a high proportion of cholesterol

Importance of fluidity in membranes

• Allows membranes to heal and fuse with each other

• E.g. vesicles can form from the membrane allowing the transport or secretion of materials

What mode is used to explain what a membrane bilayer looks like?

The fluid mosaic model

Describe the fluid mosaic model

The plasma membrane consist of:

• Lipids » contain unsaturated fatty acids

• Carbohydrates on the outer surface » can be protein linked (glycoproteins) or lipid linked (glycolipid)

• Proteins » the lipid:protein ratio can vary from 1:4 (e.g. in mitochondria) to 4:1 (e.g. in myelin sheath)

• These molecules move sideways within the membrane

• The ‘mosaic’ is held together by non-covalent interactions between lipids and proteins

2 types of membrane proteins

1. Integral » embedded in the bilayer

2. Peripheral » loosely attached to one face of the membrane, either associated to integral proteins or to the bilayer itself

What are integral proteins which span the whole bilayer referred to as?

Transmembrane proteins

» part of the protein is on the inside and the outside of the membrane

How can integral proteins only be removed?

By disruption of the membrane by detergents

How can peripheral proteins only be removed?

By mild changes in pH or ionic strength

Structure of membrane proteins

• Have hydrophobic regions which associate with the fatty acid tails of the phospholipid bilayer

• Have hydrophilic regions e.g. polar amino acids which will protrude from the membrane into the aqueous environment

What is the structure of glycoproteins?

What is their function?

• Have sugars bound to either Ser or Asp residues on the hydrophilic portion of the protein protruding from the outer leaflet of the bilayer

• These glycoproteins act as antigens by which cells are recognised as host cell rather than a foreign cell

What does it mean by biological membranes being asymmetric?

There are physical and biochemical differences between the inner leaflet (face of the bilayer in contact with the cytoplasm( and outer leaflet (face of the bilayer in contact with outside of cell/organelle)

How do lipids move within the bilayer?

• Lipids diffuse sideways within the leaflet

• But there is a high energy to transfer lipids from one side of the bilayer to the other (lipid flip-flop)

Do lipids and proteins change their orientation in the bilayer?

• Lipids: yes, can diffuse sideways

• Proteins: no, as their direction is important for their function e.g. signalling receptors must have the hormone-binding domain facing the outside of the cell to receive signals

How does a cell allow the movement of polar molecules across the bilayer?

• Using transmembrane proteins e.g. channels, pumps, gates

• These are big proteins which pass all the way through the bilayer, allowing polar compounds to pass through the middle of the protein without coming into contact with the fatty acid tails

How does a cell take up or excrete large molecules or large quantities of compounds?

• Endocytosis

• Exocytosis

Membrane Transport

Passive Diffusion

• Transfer of solutes/ions down their concentration gradient

• No energy from ATP required

• Can occur across the lipid membrane OR via channels such as aquaporins

• Facilitated passive diffusion transports large/charged/polar molecules and occurs via a carrier protein

Membrane Transport

Active Transport

• Solutes/ions transported against their concentration gradient

• Requires metabolic energy from ATP hydrolysis

• The energy from ATP is used by carrier proteins to pump a molecule from one side of the membrane to the other

• Carrier proteins have 2 binding sites: 1 for ATP, 1 for the solute

Membrane Transport

Gated Channels

• Most channels are not permanently open and have a gate which controls the opening and closing of the channel

• This is so the membrane can regulate when certain molecules are able to enter or exit

2 types:

1. Ligand-gated ion channels » channel opens in response to the binding of a particular molecule e.g. nicotinic acetylcholine receptors need to bind acetylcholine to allow the passage of ons through the channel

2. Voltage-gated ion channels » channel opens in response to a change in membrane potential e.g. ion channels in nerve cells

Types of carrier proteins

1. Uniporters: transport only 1 type of solute in one direction across the membrane

2. Co-transporters: transport 2 different solutes, so that the transport of one solute is coupled with the transfer of a second solute

Types of carrier proteins

Co-transporters

• Transport 2 different solutes, so that the transport of one solute is coupled with the transfer of a second solute

• Co-transporters move 1 solute down its concentration gradient

• This releases free energy which is then used to transport the second solute against its concentration gradient

2 types of co-transport:

1. Symporters: carry 2 solutes across the membrane in the same direction

2. Antiporters: transport 1 solute in one direction and a different solute in the opposite direction

Transport of Glucose

Where does glucose need to be transported to?

• Glucose carried from the intestines

• Across the gut epithelium

• Into the blood

• Where it is carried to tissues to make energy

Transport of Glucose

Explain how glucose is transported into the blood

1. At the epithelial cell / blood surface, the Na+/K+ ATPase antiporter uses ATP to actively transport K+ into the epithelium and Na+ out of it

2. This reduces the conc of Na+ ions inside the cell

3. Na+ moves down its concentration gradient from the gut lumen into the cell through the Na+ glucose symporter

4. This provides the free energy to bring glucose into the cell from the gut lumen against its concentration gradient

5. The concentration of glucose increases inside the epithelial cell

6. So glucose moves into the blood from the epithelial cell down its concentration gradient by facilitated diffusion via a glucose uniporter

Transport of Ca2+

What channel is involved?

What is the purpose of transporting Ca2+?

• Endoplasmic reticulum (ER) membranes contain Ca2+-ATPase

• It pumps Ca2+ ions by active transport from the cytoplasm into the ER

• This builds up a store of Ca2+ in the ER which can be released when needed for muscle contraction

Transport of Ca2+

What does the Ca2+-ATPase need to function?

• Ca2+-ATPase is an active transporter

• This means it requires ATP to function

Transport of Ca2+

Explain how ca2+ is transported from the cytoplasm into the ER

1. At first the Ca2+-ATPase channel is closed

2. But calcium binding sites are open on the cytoplasmic side of the channel, allowing Ca2+ to bind

3. ATP binds to the nucleoside binding site of the channel

4. ATP is hydrolysed to ADP and phosphate, releasing energy

5. This energy causes the conformation of the Ca2+-ATPase to change

6. This opens the channel, releasing the bound calcium into the ER lumen

7. The phosphate produced in ATP hydrolysis is hydrolysed and released from the channel

8. The channel reverts to its closed state, so Ca2+ can bind again

How are both endocytosis and exocytosis possible?

Because of membrane fluidity

Endocytosis

How does it work?

2 types

• Bulk uptake happens via endocytosis

• The membrane forms a vesicle around the particle to be taken up

1. Pinocytosis - describes the uptake of fluid in vesicles

2. Phagocytosis - describes the uptake of large particles e.g. pathogens in vesicles

Endocytosis

What is meant by receptor-mediated endocytosis?

Some molecules are selectively taken up into vesicles when they bind to a specific receptor protein on the cell surface

Endocytosis

How can the substances that enter the cell via endocytosis be digested for the use in the cell’s own metabolic processes?

Vesicles can fuse with lysosomes

Exocytosis

How does it work?

• Allows cell to excrete large particles or bulk quantities of molecules

• Vesicles containing particles to be excreted fuse with the membrane and release the particles into the extracellular space

Review Questions

1. Describe the roles and functions of lipid membranes

2. List the key characteristics of eukaryotic membranes. Why are these characteristics important for the function of the membrane

3. Summarise the main ways molecules can pass from one side of the membrane to the other. What are they key features of each route?