Membranes and Lipids 1

Question 1

What are the three different lipid types found in membranes?

Answer 1

• Glycerophospholipids
• Sphingolipids
• Sterols

Question 2

Give the basic structure of the three lipid types?

Answer 2

Glycerophospholipids: The hydrophobic regions are composed of two fatty acids joined to glycerol. One chain is either saturated or monounsaturated. The other is unsaturated. The hydrophilic region contains inorganic phosphate and varying head groups. The phosphate is bound to the fatty acids by phosphodiester bonds.

Sphingolipids: Built on sphingosine base, a single N-acyl chain (the fatty acid), phosphate and head group. Sphingolipids usually have saturated acyl chains. They have a double bond connecting the chain and the phosphate group.

Sterols: Small lipids. The overall molecule is quite flat. The hydroxyl group on the A ring is polar.

Question 3

What is membrane curvature? Why is it important?

Answer 3

Due to varying shapes of lipids, the overall shape of the membrane can change. There are 3 main types of membrane curvature:

• Cylindrical
• Conical
• Inverted conical

Bending of membranes is a requisite for the formation of spherical vesicles, which are critical components of membrane trafficking, and for changes in cell shape during cell migration and cell death. Membrane bending is also observed in cell division as the membrane pinches off during cytokinesis.

Question 4

What is the fluid mosaic model of membrane structure?

Answer 4

The model assumes that proteins are randomly distributed throughout the bilayer. It is fluid as the proteins and lipids are able to move laterally, transversely and rotationally (can spin on the spot).

Question 5

Describe membrane organisation and lipid rafts?

Answer 5

Recent evidence suggests that there are domains within the membrane. In these domains, the lipids are tightly packed. It is though these domains favour certain lipids and proteins. Depending on their size the domains can be classified into rafts, microdomains or nanodomains. This domains are probably transient and dynamic - they are formed when needed.

Question 6

Describe asymmetric distribution of phospholipid head groups and functional importance.

Answer 6

The leaflets in the bilayer do not have the same phospholipids in asymmetrical bilayers. This is functionally important, some examples include:

• Glycolipids and glycoproteins are arranged on the outer membrane as the sugar chains can be used as extracellular receptors.
• Phosphatidylserine in animal cells translocate to the extracellular monolayer when such cells undergocell death, orapoptosis. This acts as a signal to neighbouring cells, e.g. macrophages, to phagocytose the dead cell and digest it.
• Second messengers in signalling pathways are oriented towards the interior of the cell

Question 7

What is the intracellular location of triacylglycerols?

Answer 7

For example, within the liver, triacylglycerols are stored as lipid droplets in the cytoplasm adjacent to the endoplasmic reticulum. Lipid droplets are lipids enclosed in a phospholipid bilayer.

Question 8

What is the intracellular location of cholesterol esters?

Answer 8

Lysosomes and stored in cytoplasmic lipid incisions.

Question 9

What is the intracellular location of non-esterfied free cholesterol?

Answer 9

Phospholipid bilayer

Question 10

What is the role of amyloid β peptide in Alzheimer’s disease?

Answer 10

Amyloid precursor protein (APP) is a transmembrane protein thought to help the neurone grow and repair. APP is usually broken down by alpha secratase and gamma secratase. However is broken down by beta secretase and gamma secretase, it forms amyloid beta protein. This protein is insoluble and can aggregate to form plaques in the brain. These plaques are thought to be neurotoxic. They can impair the ability of neurones to transmit signals, lead to inflammation and weaken the endothelium.

Question 11

What is the link between lipid rafts, cholesterol and Alzheimer’s disease?

Answer 11

APP has shown to be higher in patients dying of CHD. Apolipoprotein E4 is vital for cholesterol transport and is also a major risk factor in Alzheimer’s disease (AD). the prevalence of AD is lower in patients on statins as statins has shown to reduce APP. Statins however do not slow the progression of AD.

Modification of the structure i of the membrane may influence the production of amyloid beta and the progression of AD. Lipid rafts promote interaction of the amyloid precursor protein (APP) with the secretase (BACE-1) responsible for generation of the amyloid β peptide, Aβ.

Question 12

What is the basic structure of membrane carbohydrates?

Answer 12

Lipids and proteins on the outer leaflet of the membrane can be glycoserated and as a result can act as receptors in cell signalling.

Question 13

What are the different types of membrane proteins?

Answer 13

I. Integral proteins - span the entire membrane. They interact with the hydrophobic regions of the bilayer and so are mad up predominately from hydrophobic amino acids.

II. Peripheral proteins - Do not interact with the hydrophobic region of the membrane. Interact with only one leaflet of the bilayer and only interact with the lipid head groups or other proteins through ionic interactions. These ionic interactions can be disrupted with a high salt concentration. e.g. cytoskeleton

III. Lipid bound proteins - Covalently bound to lipids in the membrane. As a result, these proteins are stably attached to the membrane.

Question 14

What are the different functions of the membrane proteins?

Answer 14

• The cytoskeleton - a peripheral protein that forms a scaffold on the cytosolic side of the membrane- is important in maintaining age rigidity of the cell and restricting lateral movement of the integral membrane.
• Act as receptors
• Act as effector enzymes

Question 15

How can small molecules pass passively across the membrane?

Answer 15

1. Simple diffusion: e.g. simple gases can move from a high concentration to a low concentration. Rate of diffusion is proportional to the concentration gradient.
2. Facilitated Diffusion: Moves down a concentration gradient but depends on integral membrane proteins. Does not use metabolic energy. These integral proteins have similar kinetics to enzymes i.e. they are saturable, inhibitable and have a Km value.
3. Osmosis: The movement of water molecules down a concentration gradient.

Question 16

What are the different types of ion channels proteins?

Answer 16

1. Voltage-gated ion channels e.g. Na+/K+/Ca+ channels. Activated in response to changes in the potential across the membrane. Occurs particularly in excitable cells e.g. neurones.
2. Calcium activated
3. Non-selective cation channels. The group of receptors are known as TRP receptors. Activated by lots of stimuli e.g. mechanical stimuli.

Question 17

What is an ionophore?

Answer 17

Ion channel found in bacterial membranes. Used to pump potassium ions across the membranes. This distorts the concentration gradient and so kills the competition of the bacteria. Effective as an antibiotic as it allows free movement of ions.

Question 18

How is glucose transported across the membrane?

Answer 18

• Facilitated diffusion through GLUT channels. These channel proteins have 12 transmembrane alpha helices with a central pore. Glucose is transported into Glucose-6-phosphate via hexokinase enzymes so that glucose stays in the cell as G6P cannot move across the channel.
• Na+/Glucose symport. Na+ move down its concentration gradient passively and so glucose can move in the same directly across its concentration gradient. Glucose can move across its gradient using the electrochemical energy from the movement of the ions.

Question 19

What is active transport? Give examples

Answer 19

The transport of molecules across their concentration gradient through a protein carrier. This requires energy.
Examples include:
- Sodium-potassium pump. Sodium is actively pumped into the cell and Potassium out of the cell. More Potassium is transported out compared to Sodium in. This helps to maintain a negative potential across the membrane.
- Calcium-Sodium exchange. Sodium is transported into the cell and Calcium out of the cell. Sodium moves down its concentration gradient so calcium can move against its concentration gradient. This is an antiport as the ions are moving in opposite directions.
- Sodium-glucose symport. Na+ move down its concentration gradient passively and so glucose can move in the same directly across its concentration gradient. Glucose can move across its gradient using the electrochemical energy from the movement of the ions.

Question 20

How are macromolecules transported across the membrane?

1. Exocytosis

Answer 20

1. Exocytosis
   - Constitutive endocytosis: Occurs all the time in all cells. Secreted proteins are put into vesicles which fuse with the membrane so the protein is secreted. Many proteins from the Golgi apparatus are secreted this way as well as extracellular matrix proteins.

• Regulated endocytosis: Occurs in specialised cells e.g. neuronal cells such as in the release of neurotransmitter. Regulated exocytosis as the substances are only secreted if a signal is received. For example in neuronal cells, the signal is the influx of calcium.

Question 21

What are aquaporins?

Answer 21

Channel proteins used for the movement of water across a membrane. Used two transport water in bulk; especially useful in cells that require rapid bulk transport of water. An example of this is kidney cells and cells in the intestine.

Aquaporin has six membrane-spanning alpha helical domains with both carboxylic and amino terminals on the cytoplasmic side. Aquaporins form four part clusters in the cell membrane, with each of the four monomers acting as a water channel. Each aquaporin molecules has its own pore comes together for the rapid movement of water.

Question 22

How are macromolecules transported across the membrane?

1. Endocytosis

Answer 22

1. Phagocytosis - is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome.
2. Pinocytosis - is a mode of endocytosis in which small particles suspended in extracellular fluid are brought into the cell through an invagination of the cell membrane, resulting in a suspension of the particles within a small vesicle inside the cell.
3. Receptor-mediated endocytosis - receptor proteins on the cell surface are used to capture a specific target molecule. The receptors, which are transmembrane proteins, cluster in regions of the plasma membrane known as coated pits. Clathrin is the best-studied coat protein. When the receptors bind to their specific target molecule, endocytosis is triggered, and the receptors and their attached molecules are taken into the cell in a vesicle. The coat proteins participate in this process by giving the vesicle its rounded shape and helping it bud off from the membrane.

Question 23

How is glucose transported in the intestine?

Answer 23

On the apical membrane (membrane adjacent to the lumen of the intestine), glucose moves into the epithelial cells against their concentration gradient. Glucose is able to do this using the Na+/glucose symport channel. Sodium moves down its concentration gradient into the epithelial cell. Glucose can then move down its concentration gradient into the blood using the GLUT transporters.

Question 24

What is Oral Rehydration therapy?

Answer 24

Oral Rehydration therapy is a treatment for Cholera. This is a mixture of salts and glucose - specifically sodium and potassium ions. It is used to treat severe dehydration and diarrhoea. The uptake of glucose lowers the osmotic pressure of the blood and therefore leading to the uptake of water at the intestines.

Question 25

Which plasma membrane domains are rich in cholesterol and sphingolipids?

Answer 25

Lipid drafts